A Pharmacoeconomic Evaluation of 7-Valent Pneumococcal Conjugate Vaccine in Canada

Transcription

1 MAJOR ARTICLE A Pharmacoeconomic Evaluation of 7-Valent Pneumococcal Conjugate Vaccine in Canada Marc H. Lebel, 1 James D. Kellner, 2 E. Lee Ford-Jones, 3 Kyle Hvidsten, 5 Edward C. Y. Wang, 4 Vincent Ciuryla, 6 Steve Arikian, 5 and Roman Casciano 5 1 Division of Infectious Diseases, Sainte-Justine Hospital, University of Montreal, Quebec, 2 Division of Infectious Diseases, Alberta Children s Hospital, University of Calgary, Alberta, and 3 Division of Infectious Diseases, Hospital for Sick Children, University of Toronto, Toronto, and 4 Wyeth Pharmaceuticals, Markham, Ontario, Canada; 5 The Analytica Group, New York, New York; and 6 Global Health Outcomes Assessment, Wyeth Research, Philadelphia, Pennsylvania The objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of pneumococcal conjugate vaccination for infants and children aged!5 years in Canada. A health state model incorporating incidence, vaccine efficacy, costs, and transitional probabilities for the health states (well, meningitis, bacteremia, otitis media, pneumonia, and death) was constructed for a 10-year time horizon. Implementation of a pneumococcal conjugate vaccine program in Canada for each annual birth cohort of 340,000 persons observed over 10 years would be expected to save 12 lives and 100,000 cases of pneumococcal disease over 10 years, resulting in total savings of $67 million (Canadian dollars [Can$]). Vaccination of healthy infants would result in net savings for society if the vaccine costs less than Can$50 per dose. Moreover, for a vaccine purchase price of Can$67.50, infant vaccination would cost society Can$79,000 per life-year gained. Pneumococcal conjugate vaccination is a potentially cost-effective means of pneumococcal disease prevention. Streptococcus pneumoniae, the leading cause of bacterial meningitis in children, is also a common cause of pneumonia, bacteremia, and otitis media. Children aged 6 months to 2 years have the greatest risk for invasive disease due to S. pneumoniae [1]. The 7-valent pneumococcal conjugate (PCV-7) contains the serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F, which have been estimated by the Canadian Pediatric Society (CPS) and Laboratory Center for Disease Control (LCDC) Immunization Monitoring Program, Active (IMPACT) study to represent 87% of the invasive isolates among Canadian children!2 years of age [2, 3]. Thus, an effective vaccine could make an appreciable difference Received 6 May 2002; accepted 20 October 2002; electronically published 20 January Financial support: Wyeth Research, Philadelphia, and Wyeth Pharmaceuticals, Markham, Ontario, Canada. Reprints or correspondence: Mr. Roman Casciano, The Analytica Group, 475 Park Ave. S, 17th Fl., New York, NY (rcasciano@theanalyticagroup.com). Clinical Infectious Diseases 2003; 36: by the Infectious Diseases Society of America. All rights reserved /2003/ $15.00 in morbidity and mortality. Moreover, the National Advisory Committee on Immunization in Canada has recommended that all children!2 years of age and highrisk children!5 years of age be vaccinated with PCV-7 [4]. Thus, the objective of this study was to evaluate the projected health benefits, costs, and cost-effectiveness of PCV-7 vaccination of infants and children!5 years of age in Canada. MATERIALS AND METHODS Model design. A health state transition model was designed to observe the health experiences of children in vaccinated and unvaccinated cohorts during a 10- year time period, beginning with initial vaccination. The model assumes that each patient is always in one of several distinct health states (i.e., well, meningitis, bacteremia, pneumonia, otitis media, myringotomy and ventilation tube [MVT], and death). Because it has been assumed that children are born free of pneumococcal disease, children enter the simulation in the well health state; as time progresses, they can tran- 7-Valent Pneumococcal Vaccine CID 2003:36 (1 February) 259

2 sition to the other states or remain in the same health state [5]. These transitions are based on the semiannual age-specific incidence of pneumococcal disease and the efficacy of PCV-7 in the case of vaccinated children. Incidence. Age-specific incidences for children!10 years of age were used in the PCV-7 model to quantify the occurrence of the disease over time in Canada (figure 1). The mean annual incidences per age group for Canadian children aged!10 years were 3.0 cases per 100,000 children for pneumococcal meningitis [6, 7] and 25.0 cases per 100,000 children for pneumococcal bacteremia [6, 7]. Incidences of pneumonia (on average, cases per year per 100,000 children aged!10 years) were based on Canadian data (P. DeWals, personal communication) [8]. The overall incidence of otitis media (on average, 49,000 cases per year per 100,000 children aged!10 years) was also based on Canadian data [9]. This rate was then converted into age-specific rates on the basis of Finnish data [10]. Incidences of myringotomy (1585 cases per 100,000 children aged!10 years) were obtained from an analysis of surgical procedures from Calgary, Canada [11]. Mortality rates for pneumococcal meningitis and bacteremia of 6.6 and 1.26 per 100 children, respectively, were considered in the model [3]. Vaccine efficacy rates. The model considered a vaccine efficacy rate of 89.1% for the reduction in all episodes (e.g., regardless of serotype) of pneumococcal meningitis and pneumococcal bacteremia, as observed in the Northern California Kaiser Permanente Efficacy Study (NCKPES) randomized trial [12]. In this same clinical study, the incidence of all-cause pneumonia (i.e., pneumonia caused by all pathogens, including S. pneumoniae) was reduced by 11.4%, and all-cause otitis media (i.e., otitis media caused by all pathogens, including S. pneumoniae) was reduced by 5.8% [12, 13]. Additional efficacy rates determined by the NCKPES were a 10.6% reduction in recurrent acute otitis media, a 24.9% reduction in myringotomy procedures, and a 33% reduction in episodes of radiographically confirmed pneumonia [13]. These rates, which are indicative of a lower severity in cases of pneumococcal disease observed among the vaccinated children, were considered in our study through the development of separate vaccinated and unvaccinated costs of illness to reflect this difference in disease severity and resultant cost. Immunogenicity studies of PCV-7 [14] and observational studies of the Haemophilus influenzae type b conjugate vaccine [15] suggest that PCV-7 will stimulate a long-lasting antibody response and provide an extended duration of protection to vaccinated persons. However, for purposes of the analysis, the efficacy was assumed to be 90% of the Kaiser values from the age of 6 months to 5 years as the real world value. This assumption was based on the belief that, in actual practice, factors such as population differences, infrastructure, handling of vaccine, and administration errors would reduce the efficacy from what was observed in the clinical trials (D. Scheifele, personal communication). Efficacy was then assumed to decrease by 3% per year for years 6 10 after initial vaccination, Figure 1. Annual incidences of pneumococcal diseases in Canadian children aged 0 10 years [3, 6 11]. Bacteremia and meningitis are only those cases related to Streptococcus pneumoniae (SP). MVT, myringotomy with or without pressure equalization tube insertion. 260 CID 2003:36 (1 February) Lebel et al.

3 partly as a result of age-related shifts in predominant serotypes [3]. In addition, the efficacy of the vaccine was not quantified for infants aged!6 months, but the NCKPES did reveal that the vaccine was effective for partially vaccinated children [12] and, therefore, it was assumed to be 33% effective for this age group. Because PCV-7 may be initiated at various ages according to different dosing and administration schedules, the model presents separate scenarios for both primary and catch-up vaccination schedules (table 1). Expected cost analysis. The expected cost of each health state related to a pneumococcal disease considered in the transition model was estimated by use of decision analytical modeling. A clinical management algorithm was constructed for each health state through a review of available literature and supplemented by consultation with a expert panel of Canadian experts (panel 1 in Acknowledgments) to ensure appropriate representation of current practice patterns in Canada. Clinical surveys were administered to determine treatment pathways, as well as the type and frequency of medical resources consumed for each health state in Canada. The panel provided estimates of the success and failure rates for each therapy, as well as decision nodes estimates, which represent opportunities for a physician to make a therapeutic choice in any given clinical management algorithm. A final consensus meeting, which involved a second panel of experts (panel 2 in Acknowledgements), was held to finalize the details of the clinical management analysis. Figure 2 depicts the decision trees used to determine the expected costs of the 4 pneumococcal infections considered in the model. The probability and cost (societal perspective), as well as the weighted cost of each outcome of the trees, are given for illustration. For meningitis, the long-term sequelae known to be associated with episodes of meningitis were also considered in the decision tree analysis. The probability of each complication (mental retardation, hearing loss, focal neurological deficit, and chronic seizure disorder) along with an estimate of Table 1. Dosing and administration schedules for 7-valent pneumococcal vaccine. Age at first dose (schedule) Primary series Booster dose 6 Weeks to 6 months (primary) 7 11 Months (infant catch-up) Months (toddler catch-up) 124 Months (child catch-up) 3 Doses, 8 weeks apart 2 Doses, 8 weeks apart 2 Doses, 8 weeks apart 1 Dose None 1 Dose at months 1 Dose at months None complication costs for the first year of treatments were included in the cost of illness for meningitis. Tables 2 and 3 list the unit costs (in Canadian dollars [Can$]) used to value the direct (table 2) and indirect (table 3) resources consumed in the treatment of bacteremia, as identified by the expert panel. The societal perspective includes all of the direct medical expenses accounted for in the payer analysis, as well as the direct nonmedical and indirect costs associated with the treatment of pneumococcal disease. Direct nonmedical costs include disease-related costs not borne by the health care system, such as transportation costs. A study of the direct nonmedical costs associated with episodes of simple otitis media in the United States was used to estimate the direct nonmedical costs of physician visits, hospital days, and surgeries in Canada [16]. Indirect costs are the costs associated with lost economic productivity due to morbidity or mortality. The amount of time spent in the informal care of a child with pneumococcal disease was assumed to come from a nonprofessional caregiver (e.g., parent or legal guardian). On the basis of the opinion of the expert panel, it was assumed that 4 h of productivity would be lost on the part of the nonprofessional caregiver for each outpatient physician visit or emergency department visit that is necessary for the treatment of disease. By the same method, 8 h of lost time was associated with each day spent by the child in a hospital ward, intensive care unit, and/or ambulatory surgical procedure. Each hour lost was valued through an estimate of the mean hourly wage for Ontario as given by Statistics Canada in 1997 [17] and then equated to year 2000 values. The economic value of death was calculated by determining the mean lifetime earnings of a Canadian child by use of the same hourly wage above, and an assumption of 35 h of work per week, paid employment for 50 weeks per year, and fulltime employment from the age of 20 to the age of 60. The expected future earnings lost by mortality were discounted by 3% to determine their present value. To avoid double-counting, no monetary value was attributed to death (expressed as future productivity costs) in the societal cost-effectiveness ratio. Cost-effectiveness analysis. The expected costs for the vaccinated and unvaccinated cohorts were determined with the use of the per-episode cost-of-illness estimates derived from the clinical decision tree models and the frequency of disease, on the basis of the age-specific incidence of pneumococcal disease determined in the expected health outcome analysis. From this approach, the net treatment cost or savings of a vaccination program was determined by subtracting the cost for the vaccinated cohort from the cost for the unvaccinated cohort. This net cost or savings was then equated to a per-dose vaccine cost, known as the break-even cost. The vaccine s cost-effectiveness is expressed in an incremen- 7-Valent Pneumococcal Vaccine CID 2003:36 (1 February) 261

4 Figure 2. Clinical management algorithms for bacteremia (A), meningitis (B), pneumonia (C), and acute otitis media (AOM; D). In panel A, note that admission to hospital includes admission at any point in treatment, whether on initial presentation or after treatment. Data are in Canadian dollars. Abx, antibiotics; ENT, ear-nose-throat specialist; LP, lumbar puncture; MVT, myringotomy and ventilation tube; OME, otitis media with effusion; SP, Streptococcus pneumoniae. tal cost-effectiveness (ICE) ratio, which reflects the cost per life-year gained or cost per episode of illness avoided. The ICE ratio was calculated as dollars invested in the vaccine program minus dollars saved because of averted disease episodes divided by health benefits. Each death avoided in Canada was assumed to equal the Canadian life expectancy of 78 years minus the child s age at the time of death as determined by the age-specific incidence of pneumococcal disease and its associated mortality [18]. Just as future costs are discounted, so should future benefits. Future life-years saved were discounted at 3% per year. Sensitivity analysis. The vaccine efficacy data used in the model were tested by means of a comprehensive multivariate sensitivity analysis to evaluate the sensitivity of the model to key variables by determining the impact of changes in their value on the model results. The assumptions were varied simultaneously, and results were tabulated for 10,000 different combinations of possible values. First, the efficacy rates for each of the 4 diseases were simultaneously varied across the range of the 95% CIs established by the NCKPES [12]. For example, the baseline efficacy rate for otitis media of 5.8% was varied from a lower limit of 3.7% to an upper limit of 7.8%. A second multivariate analysis was also done to test the additional impact of the uncertainty associated with the disease incidence as- 262 CID 2003:36 (1 February) Lebel et al.

5 Figure 2. (Continued.) sumptions. This analysis assumed that the disease incidence could vary within a range of 50% of the baseline values. For example, the baseline incidence for otitis media of cases per patient per year was varied from a lower limit of cases per patient per year to an upper limit of cases per patient per year. Finally, univariate analysis was conducted on the incidence of meningitis to consider the impact of including data from a source other than what was considered in the base case analysis. RESULTS Results are presented for the 10-year societal perspective analysis of the primary group (age, 0 6 months). Because strong immunologic evidence [14] indicates that this vaccine will remain largely effective throughout the 10-year time horizon of the cost-effectiveness model, the results based on this assumption are presented. Expected health outcomes results. Within each 340,000-7-Valent Pneumococcal Vaccine CID 2003:36 (1 February) 263

6 Table 2. Direct costs for resource utilization in year 2000 Canadian dollars (Can$). Direct cost Unit cost, Can$ Physician visits/hospital days Pediatric emergency department visit Follow-up pediatrician visit (established patient) Hospital day (pediatric ward) Intensive care unit day Diagnostic tests Lumbar puncture/csf analysis (including culture and antibiotic susceptibility) Blood culture and antibiotic susceptibility Urine culture and antibiotic susceptibility Complete blood cell count with differential 8.27 Renal profile (Chem-7) Chest radiography Antibiotic therapy a Oral amoxicillin Intravenous cefotaxime Intravenous ceftriaxone Intravenous cefuroxime Intramuscular ceftriaxone NOTE. Direct costs include costs of medical care incurred in the treatment of each case of illness, and direct nonmedical costs include transportation expenditures incurred to deliver medical care to patients. From: expert panel, Capra [16], 1999 Ontario Benefit Formulary (drug acquisition costs), Ontario Schedule of Benefits (physician services), Ontario Schedule of Laboratory Services (laboratory tests), the Ontario Cost Case Project, and the Canadian Institute of Health Information. Chem-7, sequential multichannel analysis with computer-7. a Costs are per milligram. birth cohort, it is expected that, during the 10 years that follow vaccination, 12 lives will be saved as well as an estimated reduction of 74 episodes of pneumococcal meningitis, 609 episodes of pneumococcal bacteremia, 8187 cases of pneumococcal pneumonia, 80,400 cases of pneumococcal otitis media, and 10,600 MVT procedures. Assuming a mean life expectancy of 78 years, the 12 avoided deaths would equate to 938 undiscounted life-years gained, or 349 discounted life-years. Table 4 displays the simulation of the health outcomes for a hypothetical birth cohort of 340,000 vaccinated primary patients and an identical cohort of unvaccinated children. Expected cost results. Table 5 presents the results of the expected cost analysis. The decreased severity of pneumonia among vaccinated children is reflected in a lower expected cost, relative to unvaccinated cases, for this health state. Pneumonia was assigned vaccinated and unvaccinated costs because it was assumed that radiographically confirmed cases of pneumonia, which were more severe than clinically observed cases, were 33% less common in the vaccinated cohort than in the unvaccinated cohort, according to the findings of the NCKPES [12]. Indirect costs and direct nonmedical costs accounted for 17% (for meningitis) to 48% (for otitis media) of the total expected cost. The lifetime earnings potential, discounted over time by 3%, was calculated to be Can$389,278 for purposes of evaluating future productivity losses. The significant reduction in the number of pneumococcal episodes will lead to savings in treatment cost. PCV-7 vaccination is expected to save Can$63 million over 10 years for each Canadian birth cohort (340,000 children) without accounting for vaccine cost and future productivity costs. This is based on the difference of the 10-year expected societal cost of the unvaccinated birth cohort (Can$899 million) and the vaccinated cohort (Can$836 million). If we divide the overall expected societal cost savings by disease state, 71% of the savings (Can$45 million) is associated with acute otitis media (including both MVT and non-mvt costs), 24% (Can$15 million) is associated with pneumonia, 3% (Can$2 million) is associated with bacteremia, and 1% (Can$1 million) is associated with meningitis. In addition, Can$3.7 million is expected to be saved in future productivity costs because of avoided deaths. Table 6 summarizes the findings of the expected cost analysis. Cost-effectiveness analysis. The resulting 10-year perpatient societal savings due to the vaccine is Can$196 (Can$66,623,995 per 340,000 children), or a per-dose breakeven cost of Can$49. This break-even cost was assumed to include the price of the vaccine plus an administration fee. Assuming a 3% discount rate for the fourth dose (12 15 months), the 10-year adjusted break-even cost was calculated at Can$50 for the societal perspective. A break-even cost was also calculated from a payer perspective and was found to be Can$27. At an assumed cost of Can$67.50 per dose, the 10-year PCV-7 incremental cost-effectiveness ratio was determined to be Can$29,287 per life-year gained from a societal perspec- Table 3. Indirect costs for resource utilization in year 2000 Canadian dollars (Can$). Indirect cost Time, h Cost, Can$ Total cost, Can$ Pediatric emergency department visit Follow-up pediatrician visit (established patient) Hospital day (pediatric ward) Intensive care unit day Transportation cost NOTE. Indirect costs include estimated costs of lost wages for caregivers, and direct nonmedical costs include transportation expenditures incurred to deliver medical care to patients. From expert panel, Capra [16], 1999 Ontario Benefit Formulary (drug acquisition costs), Ontario Schedule of Benefits (physician services), Ontario Schedule of Laboratory Services (laboratory tests), the Ontario Cost Case Project, and the Canadian Institute of Health Information. 264 CID 2003:36 (1 February) Lebel et al.

7 Table 4. Expected health outcomes for a simulated number of cases of each infection at 10-year time horizon in Canada for a hypothetical birth cohort of 340,000 children. Patient type No. of cases Bacteremia Meningitis Pneumonia Otitis media Myringotomy Total no. of cases of disease Primary vaccinated ,908 1,591,114 43,272 1,713,564 5 Primary unvaccinated ,095 1,671,532 53,871 1,813, Outcomes avoided ,418 10,599 99, No. of deaths tive or Can$78,778 with 3% discounting for future years: (Can$926,000,000 Can$ 899,000,000)/(938 or 349 life-years gained). The ICE ratio from a payer perspective was determined to be Can$154,591 per discounted life-year gained. To avoid double counting, future productivity costs were not included in the societal cost-effectiveness ratio. The ICE ratio values for discounted life-years gained from both societal and payer perspectives are presented in figure 3. Incremental cost-effectiveness analysis per illness avoided from a societal perspective at Can$67.50 per dose of PCV-7 resulted in an ICE ratio of Can$275 per illness avoided. Catch-up populations. An analysis of the 3 catch-up populations was also done. For children who receive initial vaccination during the age of 7 11 months (catch-up 1: 3-dose schedule), break-even costs were calculated at Can$35 (payer) and Can$64 (societal). Break-even costs were determined at Can$47 (payer) and at Can$87 (societal) for the second catchup population evaluated in this study (12 23 months, 2-dose schedule). Finally, children receiving vaccination during the age of 2 5 years (catch-up 3: 1-dose schedule) had break-even costs calculated from a payer perspective at Can$54 and Can$94 from a societal perspective over a 10-year time horizon. Sensitivity analysis. A multivariate sensitivity analysis of the patient-level societal perspective results was conducted. The 95% CI of the cost per undiscounted life-year gained results was calculated to be Can$16,415 Can$39,633 when only the assumptions regarding efficacy were varied. The additional variation of disease incidence by 50% increased the 95% CI to a lower limit of Can$1568 and an upper limit of Can$71,106. A univariate sensitivity analysis of these same results was done to consider the impact of use of a higher rate of meningitis, as indicated by a recent study [3]. The expected number of meningitis cases avoided was increased to 96 and the expected deaths avoided increased to 14 (1028 life-years) for a cohort of 340,000 children. The cost per life-year gained decreased to Can$26,457 per life year gained. DISCUSSION Routine vaccination of Canadian infants with PCV-7 has the potential to significantly reduce the burden of pneumococcal diseases. Given the high morbidity and mortality of pneumococcal diseases among children!5 years of age, and considering that the current 23-valent pneumococcal vaccine is not immunogenic for children!2 years of age, universal vaccination with PCV-7 among Canadian children, as recommended by the recently released statement from National Advisory Committee on Immunization in Canada, warrants serious consideration. The current analysis finds that vaccination of an annual Canadian birth cohort of 340,000 children is expected to save 12 lives as well as to avoid almost 100,000 cases of pneumococcal disease over 10 years including 74 cases of meningitis, 609 cases of bacteremia, and cases of pneumonia and 80,000 cases of acute otitis media. Numerous clinical, humanistic, and economic benefits associated with vaccination with PCV-7 could not be included in this evaluation because of lack of long-term data. Without vaccination, the trend of antibiotic resistance may cause greater morbidity and mortality as well as significantly increase the cost of treatment for S. pneumoniae related illnesses in Canada [19 21]. By 1998, 13% of invasive pediatric isolates across Canada had reduced penicillin susceptibility [22], and a survey of Table 5. Expected cost analysis per case in year 2000 Canadian dollars (Can$). Event Cost per case, Can$ (percentage of total cost per case) Direct medical cost Indirect cost Direct nonmedical cost Bacteremia 1928 (69) 764 (28) 87 (3) Meningitis 12,867 (83) 2370 (15) 305 (2) Pneumonia Vaccinated patients 665 (63) 340 (32) 51 (5) Unvaccinated patients 736 (64) 368 (32) 54 (5) Otitis media 262 (52) 207 (41) 35 (7) Myringotomy 572 (65) 277 (31) 36 (4) NOTE. From expert panel, Capra [16], 1999 Ontario Benefit Formulary (drug acquisition costs), Ontario Schedule of Benefits (physician services), Ontario Schedule of Laboratory Services (laboratory tests), the Ontario Cost Case Project, and the Canadian Institute of Health Information. Direct costs include costs of medical care incurred in the treatment of each case of illness, indirect costs include estimated costs of lost wages for caregivers, and direct nonmedical costs include transportation expenditures incurred to deliver medical care to patients. 7-Valent Pneumococcal Vaccine CID 2003:36 (1 February) 265

8 Table 6. Projected 10-year costs with and without a routine pneumococcal conjugate vaccination program for 340,000 healthy Canadian infants. Cost category Cost for unvaccinated population Cost for vaccinated population Cost of (savings associated with) vaccination Pneumococcal disease associated Bacteremia (1.6) Meningitis (1.1) Pneumonia (15.4) Otitis media (36.6) Myringotomy (8.4) Total disease costs (63.0) Direct costs (36.6) Indirect and direct nonmedical costs (26.4) Future productivity costs (3.7) Vaccination program costs (societal), by per-dose cost of vaccine Can$ (66.6) Can$ Can$ NOTE. Data are cost in millions of year 2000 Canadian dollars (Can$). clinical isolates recovered from persons of all ages across Canada in 2000 found that 12% had reduced susceptibility to penicillin, 11% were resistant to erythromycin, and 11% were resistant to trimethoprim-sulfamethoxazole [23]. Although pneumococcal conjugate vaccines have been shown to prevent the emergence of antibiotic-resistant strains of S. pneumoniae [19], we did not account for that factor in this evaluation. Similarly, vaccination of children with the 9-valent pneumococcal conjugate vaccine has been shown to reduce the transmission of S. pneumoniae and antibiotic-resistant S. pneumoniae, especially to their siblings [20]. In addition, postlicensure surveillance for invasive pneumococcal infections in northern California has found that reductions in disease rates exceeded the average vaccine coverage substantially, which is indirect evidence of herd immunity [21]. Despite the evidence, the extent to which herd immunity with PCV-7 vaccination prevents infections remains unknown and therefore is not included in this analysis. Figure 3. Incremental cost-effectiveness of 7-valent pneumococcal vaccine, at varying vaccine cost per dose, for healthy Canadian infants. Costs are in year 2000 Canadian dollars (Can$), assuming a discount rate of 3% per year for future costs as well as life-years. 266 CID 2003:36 (1 February) Lebel et al.

9 PCV-7 s efficacy was measured against only 4 pneumococcal diseases (meningitis, bacteremia, pneumonia, and otitis media), although many other pneumococcal diseases exist. S. pneumoniae is known to cause osteomyelitis, septic arthritis, sinusitis, endocarditis, and peritonitis, so it is reasonable to assume that the morbidity and costs associated with these diseases have the potential to add to the existing model. In addition, intangible costs (e.g., pain and quality of life) were not considered in the analysis Several limitations are inherent to the model design. Because a cohort-based model was used for the study, we were unable to account for all possible patient variations, such as subgroup variations and individual patient characteristics. Therefore, the results of this pharmacoeconomic study attempt to reflect the outcomes for the average patient; however, the significant individual patient variations and differences in practice patterns may compromise the external validity of the evaluation. Specifically, the exclusion of at-risk patients, such as immunocompromised or asplenic children, may affect the potential economic benefits of PCV-7. Another consequence of the model s structure is that a member of the cohort cannot occupy 11 disease state within a time cycle. Therefore, coexisting pneumococcal infections were not considered in this analysis. Similarly, the model used in this study is not appropriate to fully characterize chronic illnesses, such as mental retardation, hearing loss, focal neurological deficit, and chronic seizure disorder that occurs after meningitis. The current study was conducted in a Canadian-specific context to account for potential population differences that may exist between Canada and other countries. However, our findings concur with those of a US study, which found that pneumococcal conjugate vaccination of healthy infants has the potential to be cost-effective from a societal perspective [24]. More specifically, the present study found that, for a vaccine purchase cost of Can$67.50 per dose, the cost per life-year gained would be Can$79,000. Cost-effectiveness ratio values similar to those determined in the present study can be found for other health interventions currently used in Canada [25]. Prevention of morbidity and mortality due to pneumococcal disease play equally important roles in the pediatric population. Thus, the decision to implement an effective vaccine program with the potential to rapidly make an appreciable difference should not be based solely on quantitative economic factors but also on qualitative health improvements. We conclude that routine vaccination with PCV-7 has the potential to be costeffective for the healthy Canadian infant population. Acknowledgments We acknowledge the contribution of the expert panels. Panel 1 comprised Francisco Noya (Montreal Children s Hospital), Blake Papsin (Hospital for Sick Children; Toronto), Mel Schloss (Montreal Children s Hospital), Mitchell Shiller (Montreal Children s Hospital), and Bruce Tapiero (Hôpital Sainte-Justine; Montreal). Panel 2 comprised François Boucher (Centre de l Université Laval; Quebec City, Quebec), Lee Ford-Jones (Hospital for Sick Children), Scott Halperin (IWK Grace Health Centre; Halifax, Nova Scotia), Marc Lebel (Hôpital Sainte Justine), and Allison McGeer (Mount Sinai Hospital; Toronto). 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