Bridging health technology assessment (HTA) and efficient health care decision making with multicriteria decision analysis (MCDA): applying the EVIDEM framework to medicines appraisal.

BACKGROUND: Health care decision making is complex and requires efficient and explicit processes to ensure transparency and consistency of factors considered. OBJECTIVES: To pilot an adaptable decision-making framework incorporating multicriteria decision analysis (MCDA) in health technology assessment (HTA) with a pan-Canadian group of policy and clinical decision makers and researchers appraising 10 medicines covering 6 therapeutic areas. METHODS: An appraisal group was convened and participants were asked to express their individual perspectives, independently of the medicines, by assigning weights to each criterion of the MCDA core model: disease severity, size of population, current practice and unmet needs, intervention outcomes (efficacy, safety, patient reported), type of health benefit, economics, and quality of evidence. Participants then assigned performance scores for each medicine using available evidence synthesized in a "by-criterion" HTA report covering each of the MCDA CORE model criteria. MCDA estimates of perceived value were calculated by combining normalized weights and scores. Feedback on the approach was collected through structured discussion. RESULTS: Relative weights on criteria varied widely, reflecting the diverse perspectives of participants. Scores for each criterion provided a performance measure, highlighting strengths and weaknesses of each medicine. MCDA estimates of perceived value ranged from 0.42 to 0.64 across medicines, providing comprehensive measures incorporating a large spectrum of criteria. Participants reported that the framework provided an efficient approach to systematic consideration in a pragmatic format of the multiple elements guiding decision, including criteria and values (MCDA core model) and evidence (HTA "by-criterion" report). CONCLUSIONS: This proof-of-concept study demonstrated the usefulness of incorporating MCDA in HTA to support transparent and systematic appraisal of health care interventions. Further research is needed to advance MCDA-based approaches to more effective healthcare decision making.

Cost-effectiveness of a 3-dose pneumococcal conjugate vaccine program in the province of Quebec, Canada.

In the province of Quebec, Canada, the pneumococcal 7-valent conjugate vaccine (PCV-7) was licensed in 2001 and a publicly funded program was implemented in 2004, recommending 3 doses for healthy children. An economic analysis was performed both from a health care and societal perspective. Outcomes possibly prevented by PCV-7 and observed in 2006-2007 were compared to expected frequencies based on rates measured before PCV-7 use. Annual program costs were close to $21M for the health system and $23M for society. Approximately 20,000 infections were prevented annually and estimated economic benefits were $5M for the health system and $23M for society, using a 3% per annum discounting rate. The incremental cost-effectiveness ratio was $18,000 per QALY gained for the health system and the program was close to the break-even threshold in a societal perspective.

How to compare the efficacy of conjugate vaccines to prevent acute otitis media?

Although the currently available 7-valent pneumococcal conjugate vaccine (PCV7-CRM(197)) has been primarily designed for the prevention of invasive pneumococcal disease, it has also demonstrated the potential to prevent acute otitis media (AOM) and its associated complications. A candidate 11-valent pneumococcal conjugate vaccine (PCV11-HiD), which utilizes Haemophilus influenzae (Hi)-derived protein D as a carrier has demonstrated the ability to prevent AOM caused by not only vaccine serotypes of Streptococcus pneumoniae (Sp), but also those caused by Hi. The methodological, clinical, and epidemiological factors influencing results of vaccine trials for AOM prevention were reviewed and a model-based approach was developed, in order to assess the relative efficacy of different vaccine formulations. Six randomized trials having AOM as a measured outcome were identified. Vaccine efficacy (VE) ranged from -1% to 34% for all-cause AOM and between 56% and 64% for AOM caused by vaccine-type Sp. Using otopathogen-specific VE rates from the FinOM and POET trials and otopathogen distributions observed in three relatively unbiased studies, VE against all-cause AOM episodes under different scenarios was modeled. The most important factor explaining variation in VE estimates was bacterial replacement, which was present in the PCV7-CRM(197) FinOM study but not in the PCV11-HiD POET study. Another contributing factor was increased protection conferred against Hi AOM by protein D. Geographical variation in the distribution of otopathogens was a third factor explaining differences between trials. More studies on the current aetiology of AOM need to be performed to accurately predict the marginal benefit of a switch from PCV7-CRM(197) to the newly licensed PCV10-HiD-DiT or to the future PCV13-CRM(197).

Evidence and Value: Impact on DEcisionMaking--the EVIDEM framework and potential applications.

BACKGROUND: Healthcare decisionmaking is a complex process relying on disparate types of evidence and value judgments. Our objectives for this study were to develop a practical framework to facilitate decisionmaking in terms of supporting the deliberative process, providing access to evidence, and enhancing the communication of decisions. METHODS: Extensive analyses of the literature and of documented decisionmaking processes around the globe were performed to explore what steps are currently used to make decisions with respect to context (from evidence generation to communication of decision) and thought process (conceptual components of decisions). Needs and methodologies available to support decisionmaking were identified to lay the groundwork for the EVIDEM framework. RESULTS: A framework was developed consisting of seven modules that can evolve over the life cycle of a healthcare intervention. Components of decision that could be quantified, i.e., intrinsic value of a healthcare intervention and quality of evidence available, were organized into matrices. A multicriteria decision analysis (MCDA) Value Matrix (VM) was developed to include the 15 quantifiable components that are currently considered in decisionmaking. A methodology to synthesize the evidence needed for each component of the VM was developed including electronic access to full text source documents. A Quality Matrix was designed to quantify three criteria of quality for the 12 types of evidence usually required by decisionmakers. An integrated system was developed to optimize data analysis, synthesis and validation by experts, compatible with a collaborative structure. CONCLUSION: The EVIDEM framework promotes transparent and efficient healthcare decisionmaking through systematic assessment and dissemination of the evidence and values on which decisions are based. It provides a collaborative framework that could connect all stakeholders and serve the healthcare community at local, national and international levels by allowing sharing of data, resources and values. Validation and further development is needed to explore the full potential of this approach.

Vaccinating adolescents against meningococcal disease in Canada: a cost-effectiveness analysis.

BACKGROUND: One dose of serogroup C meningococcal conjugate vaccine (MCV-C) at 12 months of age is the most common immunization schedule in Canada, but immunity may wane over time. OBJECTIVES: To assess the cost-effectiveness of a booster dose at 12 years of age with either MCV-C or a quadrivalent ACYW135 meningococcal conjugate vaccine (MCV-4). METHODS: A simulation model for assessing both the direct and indirect effects of vaccination was developed. Age- and serogroup-specific incidence and fatality rates were derived from Canadian surveillance data. Vaccine efficacy was estimated from data from the U.K. 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 MCV-C and $70 for MCV-4. Costs and health outcomes were discounted at 3% per year. Results, expressed in 2004 Canadian $ and from a societal perspective, were presented for a steady state situation and a population of 1 million. RESULTS: Under the "no vaccination" base scenario, 5.7 cases of vaccine-preventable meningococcal disease would occur each year. Vaccination at 12 months using MCV-C would reduce the burden of disease by 32%. Adding MCV-C at 12 years of age would reduce the number of cases by 55% at no marginal cost, while using MCV-4 would result in a disease reduction of 78% for a marginal cost of $31000 per QALY gained. Comparing MCV-4 with MCV-C as a booster dose, the incremental cost-effectiveness ratio would be $113000 per QALY. The efficacy of C-MCV vaccination at 12 months 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 will improve the marginal cost-effectiveness ratio associated with MCV-4. CONCLUSION: Adolescent revaccination would be beneficial. Using C-MCV would be the most cost-effective option, while using MCV-4 would be more effective but would also require more investment.

The burden of pneumococcal disease in the Canadian population before routine use of the seven-valent pneumococcal conjugate vaccine.

BACKGROUND: In the United States, implementation of the seven-valent conjugate vaccine into childhood immunization schedules has had an effect on the burden of pneumococcal disease in all ages of the population. To evaluate the impact in Canada, it is essential to have an estimate of the burden of pneumococcal disease before routine use of the vaccine. METHODS: The incidence and costs of pneumococcal disease in the Canadian population in 2001 were estimated from various sources, including published studies, provincial databases and expert opinion. RESULTS: In 2001, there were 565,000 cases of pneumococcal disease in the Canadian population, with invasive infections representing 0.7%, pneumonia 7.5% and acute otitis media 91.8% of cases. There were a total of 3000 deaths, mainly as a result of pneumonia and largely attributable to the population aged 65 years or older. There were 54,330 life-years lost due to pneumococcal disease, and 37,430 quality-adjusted life-years lost due to acute disease, long-term sequelae and deaths. Societal costs were estimated to be $193 million (range $155 to $295 million), with 82% borne by the health system and 18% borne by families. Invasive pneumococcal infections represented 17% of the costs and noninvasive infections represented 83%, with approximately one-half of this proportion attributable to acute otitis media and myringotomy. CONCLUSIONS: The burden of pneumococcal disease before routine use of the pneumococcal conjugate vaccine was substantial in all age groups of the Canadian population. This estimate provides a baseline for further analysis of the direct and indirect impacts of the vaccine.

Cost-effectiveness of drug-eluting coronary stents in Quebec, Canada.

OBJECTIVES: The aim of this investigation was to assess the incremental cost-effectiveness of replacing bare metal coronary stents (BMS) with drug-eluting stents (DES) in the Province of Quebec, Canada. METHODS: The strategy used was a cost-effectiveness analysis from the perspective of the health-care provider, in the province of Quebec, Canada (population 7.5 million). The main outcome measure was the cost per avoided revascularization intervention. RESULTS: Based on the annual Quebec rate of 14,000 angioplasties with an average of 1.7 stents per procedure and a purchase cost of $2,600 Canadian dollar (CDN) for DES, 100 percent substitution of BMS with DES would require an additional $45.1 million CDN of funding. After the benefits of reduced repeat revascularization interventions are included, the incremental cost would be $35.2 million CDN. The cost per avoided revascularization intervention (18 percent coronary artery bypass graft, 82 percent percutaneous coronary intervention [PCI]) would be $23,067 CDN. If DES were offered selectively to higher risk populations, for example, a 20 percent subgroup with a relative restenosis risk of 2.5 times the current bare metal rate, the incremental cost of the program would be $4.9 million CDN at a cost of $7,800 per avoided revascularization procedure. Break-even costs for the program would occur at DES purchase cost of $1,161 for 100 percent DES use and $1,627 for selective 20 percent DES use for high-risk patients for restenosis (RR = 2.5). Univariate and Monte Carlo sensitivity analyses indicate that the parameters most affecting the analysis are the capacity to select patients at high risk of restenosis, the average number of stents used per PCI, baseline restenosis rates for BMS, the effectiveness ratio of restenosis prevention for DES versus BMS, the cost of DES, and the revascularization rate after initial PCI. Sensitivity analyses suggest little additional health benefits but escalating cost-effectiveness ratios once a DES penetration of 40 percent has been attained. CONCLUSIONS: Under current conditions in Quebec, Canada, selective use of DES in high-risk patients is the most acceptable strategy in terms of cost-effectiveness. Results of such an analysis would be expected to be similar in other countries with key model parameters similar to those used in this model. This model provides an example of how to evaluate the cost-effectiveness of selective use of a new technology in high-risk patients.

Cost-effectiveness of immunization strategies for the control of serogroup C meningococcal disease.

This study compares the cost-effectiveness of a control strategy for serogroup C meningococcal disease (CMD) relying on surveillance and implementation of a mass immunization campaign effective 1 year after the beginning of an epidemic with strategies based on routine immunization, using either three doses of serogroup C conjugate vaccine given in early infancy or one dose at 1 year of age. The simulation model is based on 25 birth cohorts followed up to age 24 years, and seven epidemiological scenarios including low and high level endemicity, and one to five epidemics over a 49-year period. Epidemiological and cost data were mainly collected in the province of Quebec, Canada. Results indicate that the most effective strategy is a three-dose routine program, with the least effective strategy being mass immunization. A one-dose routine program is the most cost-effective strategy in most likely scenarios. In a societal perspective with a vaccine purchase price of CDN$ 50 per dose, the average incremental cost of the one-dose strategy would be $ 190,000 per case averted, US$ 23,000 per life-year gained, and US$ 42,000 per QALY gained. If vaccine-induced immunity is waning rapidly, mass immunization or routine vaccination with booster dose(s) would be the best control options.

Benefits and costs of immunization of children with pneumococcal conjugate vaccine in Canada.

To estimate cost-effectiveness of routine and catch-up vaccination of Canadian children with seven-valent pneumococcal conjugate vaccine, a simulation model was constructed. In base scenario (vaccination coverage: 80%, and vaccine price: 58 dollars per dose), pneumococcal disease incidence reduction would be superior to 60% for invasive infections, and to 30% for non-invasive infections, but the number of deaths prevented would be small. Annual costs of routine immunization would be 71 million dollars (98% borne by the health system). Societal benefit to cost ratio would be 0.57. Net societal costs per averted pneumococcal disease would be 389 dollars and 125,000 per life-year gained (LYG). Vaccine purchase cost is the most important variable in sensitivity analyses, and program costs would be superior to societal benefits in all likely scenarios. Vaccination would result in net savings for society, if vaccine cost is less than 30 dollars per dose. Economic indicators of catch-up programs are less favorable than for routine infant immunization.

Epidemiological and economic burden of pneumococcal diseases in Canadian children.

BACKGROUND: With the arrival of a new conjugate pneumococcal vaccine, it is important to estimate the burden of pneumococcal diseases in Canadian children. The epidemiological data and the economic cost of these diseases are crucial elements in evaluating the relevance of a vaccination program. METHODS: Using provincial databases, ad hoc surveys and published data, age-specific incidence rates of pneumococcal infections were estimated in a cohort of 340,000 children between six months and nine years of age. The costs of these diseases to the health system and to families were also evaluated using data from Quebec and Manitoba. RESULTS: Cumulative risks were one in 5000 for pneumococcal meningitis, one in 500 for bacteremia and one in 20 for pneumonia, leading to 16 deaths in the cohort. About 262,000 otitis media episodes and 32,000 cases of myringotomy with ventilation tube insertion were attributable to Streptococcus pneumoniae. Societal costs were estimated at $125 million, of which 32% was borne by the health system and 68% was borne by families. Invasive infections represented only 2% of total costs, while 84% were generated by otitis media. CONCLUSION: Pneumococcal infections represent a significant burden for Canadian children and society that could be significantly reduced through immunization.

Vaccinating first-year college students living in dormitories for Meningococcal disease: an economic analysis.

BACKGROUND: Surveillance of meningococcal disease among U.S. college students found an elevated rate of this disease among first-year students living in dormitories. OBJECTIVE: This study examines the economics of routinely vaccinating a cohort of 591,587 incoming first-year students who will live in dormitories for > or =1 years. METHODS: A cost-benefit model (societal perspective) was constructed to measure the net present value (NPV) of various vaccination scenarios, as well as the cost/case and cost/death averted. Input values included hospitalization costs from $10,924 to $24,030 per hospitalization; immunization costs (vaccine plus administration costs) from $54 to $88 per vaccine; 30 nonfatal, vaccine-preventable cases over a 4-year period (includes 3 with sequelae); 3 premature deaths; value of human life from $1.2 million to $4.8 million; and long-run sequelae costs from $1298 to $14,600. Sensitivity analyses were also conducted on vaccine efficacy (80% to 90%); discount rate (0% to 5%); and coverage (60% to 100%). RESULTS: The costs of vaccination outweighed the benefits gained with NPVs ranging from -$11 million to -$49 million. The net cost per case averted ranged from $0.6 million to $1.9 million. The net cost per death averted ranged from $7 million to $20 million. The break-even costs of vaccination (when NPV=$0) at 60% coverage ranged from $23 (90% vaccine efficacy) to $5 (80% efficacy). CONCLUSIONS: The model showed that the vaccination program is not cost-saving. Key variables influencing the results were the low number of vaccine-preventable cases and the high cost of vaccination. However, from the perspective of students and parents, the cost of vaccination might be worth the real or perceived benefit of reducing the risk to an individual student of developing meningococcal disease.

Economic analysis of the 1992-1993 mass immunization campaign against serogroup C meningococcal disease in Quebec.

The objective of the study was to evaluate the cost-effectiveness and utility of the mass immunization campaign performed in the province of Quebec in 1992-1993, following an outbreak of serogroup C meningococcal disease (CMD). Effectiveness data were extracted from a population-based cohort study, and cost estimates were obtained from surveys. Costs of the campaign to the health system were $ 26 million (1993 Canadian dollars). Between 48 and 74 CMD cases, and between 7 and 11 deaths were prevented in the following 5 years. Net societal costs were between $ 18 and 21 million (using a 3% discount rate), net costs per death averted were between $ 1.7 and 3.0 million, between $ 58,000 and 105,000 per life-year gained, and between $ 49,000 and 87,000 per quality-adjusted life-year gained. These economic indices are less favorable than those for current routine immunization programs in Canada, but within the range of those for other common health interventions.