CPHA 2010 Potential Health and Economic Impact of new Pneumococcal Vaccines Against Acute Otitis Media in Canada Afisi S. Ismaila a,b, Jennifer A. Pereira c, Reid C. Robson a, Gerhart Knerer d a Medical Affairs, GlaxoSmithKline Canada, Mississauga, ON, Canada b Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada c Ontario Agency for Health Protection and Promotion (OAHPP), Toronto, Canada c Global Clinical Research and development (GCRD), GlaxoSmithKline Biologicals, Wavre, Belgium June 15, 2009
Outline Background Methods Results Conclusions
Outline Background Methods Results Conclusions
Background Acute otitis media (AOM) is extremely common in young children, with more than 80% having at least one episode by 3 years of age 1. Streptococcus pneumoniae (Sp) and non-typeable Haemophilus influenzae (NTHi) are the two most commonly isolated pathogens in AOM cases 2,3. Recently, the proportion of AOM episodes caused by Sp has decreased, whereas the proportion of AOM episodes caused by NTHi has increased 4,5. Routine childhood immunization programs in Canada currently include Prevnar (PCV-7) and Synflorix TM (PHiD-CV) pneumococcal vaccines. Prevnar-13 (PCV-13) was recently licensed in Canada. 1 Teele et al., J Infect Dis 1990; 162(3); 2 Bluestone et al; Pediatr Infect Dis J 1992;11(8 Suppl):7 11; 3 Heikkinen et al.; N Engl J Med 1999;340(4):260 4; 4 Casey and Pichichero; Pediatr Infect Dis J.2004;23(9):824 828; 5 Block et al.;. Pediatr Infect Dis J. 2004;23(9):829 833
Pneumococcal conjugate vaccines Vaccine serotypes PCV-7 4, 6B, 9V, 14, 18C, 19F, 23F Synflorix 4, 6B, 9V, 14, 18C, 19F, 23F 1, 5, 7F NTHi PCV-13 4, 6B, 9V, 14, 18C, 19F, 23F 1, 5, 7F 3, 6A, 19A Cross-reactive serotypes 1,2,3,4 6A 19A 1. Whitney et al. Lancet 2006; 368: 495 502; 2. Vakevainen et al. (J Infect Dis 2001;184:789 93); 3. Jakobsen et al. (Infec & Immun 2003: 2956 2959); 4. Hausdorff et al. (BMC peadtrics)
Objective To estimate the potential impact of universal infant vaccination with PHiD-CV compared with PCV-7 and PCV- 13 on the burden of AOM in children less than 10 years old in Canada.
Outline Background Methods Results Conclusions
Model Description We used a recently published static, deterministic, agecompartmental, population model 1. Simulates both direct and indirect effect of vaccination at steady-state for only one year across whole population Three vaccination scenarios: PCV-7, PHiD-CV and PCV-13 Two vaccination schedules: 2+1 and 3+1 Both health system and societal perspectives were considered 1 De Wals et al., Clin Ther. 2009 Oct;31(10):2152-69.
Input variables and data The population modeled is children less than 10 years (approximately 3.6 million) 1. The vaccinated population is children aged 2 to 13 months (348,000). Vaccination cost was set at parity ($70) per dose plus administration for all vaccines. The model used Canada-specific epidemiological data 2-9 1 Statistics Canada: http://www40.statcan.ca/l01/cst01/demo10a.htm (Oct. 2008). 2 Bettinger et al.: Can J Public Health. 2007 Mar-Apr;98(2):111-115. 3 MADO 2004 (Maladies infectieuses a declaration obligatoire). 4 Morrow et al., Can J Infect Dis Med Microbiol 2007;18:121-27. 5 Petit et al.: Can J Infect Dis 2003;14:215-20. 6 Robinson et al.: JAMA 2001;285(13):1729-35. 7 Scheifele et al.: Clin Infect Dis. 2000;31(1):58-64. 8 Shariatzadeh et al.: Medicine 2005;84(3):147-61. 9 Furlong et al.: Ann Med 2001;33(5):375-84.
Key model assumptions for base case: (Direct Effect) Disease Outcomes PCV-7 3+1 Regimen Reduction in AOM caused by vaccine serotypes 1,2 57.2 (44.0, 67.0) Reduction in AOM caused 33.0 by non-vaccine serotypes 1 ( 80.0, 1.0) Reduction in AOM due to 11.0 NTHi 1,2 ( 34.0, 8.0) PHiD-CV 3+1 Regimen 57.6 (41.4, 69.3) 33.0 ( 80.0, 1.0) 35.6 (3.8, 57.0) PCV-13 3+1 Regimen 57.2 (44.0, 67.0) 33.0 ( 80.0, 1.0) 11.0 ( 34.0, 8.0) Percent of AOM cases covered by vaccine 68.2 71.6 82.2 serotypes 3 Maximal reduction in allcause myringotomy procedures 4 19.2 65.8 32.22 35.9% of AOM cases were assumed to have been attributable to Sp, and 32.3% to NTHi 5 1 Eskola et al.; N Engl J Med 2001;344(6):403-9; 2 Prymula et al;. Lancet 2006;367(9512):740-8. 3 Hausdorff et al; Pediatr Infect Dis J 2002;21(11):1008-16; 4 Black et al; Pediatr Infect Dis J 2000;19(3):187-95; 5 Leibovitz et al; Pediatr Infect Dis J 2004;23(12):1142-52.
Maximal vaccine effectiveness VEff = (VE VT % of AOM cases due to vaccine serotypes) + (VE NVT % of AOM cases due to nonvaccine serotypes) + (VE NTHi % of AOM cases due to NTHi) where VEff = vaccine effectiveness, VE VT = vaccine efficacy on vaccine serotypes, VE NVT = vaccine efficacy on nonvaccine serotypes, VE NTHi = vaccine efficacy on disease caused by NTHi.
Other model assumptions We assume vaccine price parity of $70 per dose, 100% vaccination coverage and no herd protection Both 3+1 (2, 4, 6 and 12 to 18 months) and 2+1 (2, 4, and 12 to 18 months) vaccination schedules were considered. For 2 + 1 schedules, it was assumed that efficacy from the second dose would last 2 months and then would decrease to zero until the booster dose was given, at which point the efficacy against AOM would be the same as that reported for the 3 + 1 schedule 1. Vaccine effectiveness is assumed to wane by age, peaking once all doses are received (12 to 18 months) then waning starts a year later. 1 Fireman et al.pediatr Infect Dis J. 2003;22:163.
Outline Background Methods Results Conclusions
Estimated maximal effectiveness against all-cause AOM (children less than 10 years)
Calculated vaccine effectiveness for all-cause Myringotomy (children less than 10 years)
Base case results: effectiveness Outcome Measures AOM Myringotomy GP visits for AOM Total antibiotic prescriptions for AOM No. of outcomes with No Vaccinatio n Number of outcomes prevented vs. no vaccination 2 + 1 Regimen 3+1 regimen PCV-7 PHiD-CV PCV-13 PCV-7 PHiD-CV PCV-13 34164 2,699 9,255 4,529 4,045 13,872 6,787 1,645,367 46,224 158,518 77,562 70,456 241,618 118,223 1,390,335 39,060 133,948 65,540 59,536 204,167 99,898
Base case results: direct cost Costs in million dollars (Canadian) Inpatient costs (Myringotomy) Outpatient costs (GP visits) Total direct AOM cost No Vaccinatio n Total savings versus no vaccination 2 + 1 Regimen 3+1 regimen PCV-7 PHiD-CV PCV-13 PCV-7 PHiD-CV PCV-13 $20.3 $1.6 $5.5 $2.7 $2.4 $8.2 $4.0 $108.6 $3.1 $10.5 $5.1 $4.7 $16.0 $7.8 $128.7 $4.7 $16.0 $7.8 $7.1 $24.2 $11.8
Base case results: indirect cost Costs in Millions Cost of wages lost due to AOM GP visits Cost of wages lost due to myringotomy procedures Total Indirect AOM cost No Vaccination Total savings versus no vaccination 2 + 1 Regimen 3+1 regimen PCV-7 PHiD-CV PCV-13 PCV-7 PHiD-CV PCV-13 $227.2 $6.4 $21.9 $10.7 $9.7 $33.3 $16.3 $4.7 $0.4 $1.3 $0.6 $0.6 $1.9 $0.9 $231.9 $6.8 $23.2 $11.3 $10.3 $35.3 $17.2
Outline Background Methods Results Conclusions
Limitations The effectiveness of both PHiD-CV and PCV-13 was estimated from their predecessors (PCV-7 or the 11-valent PHiD-CV). The accuracy of these estimations may need to be validated in future studies. AOM-related sequelae have not been included in the analysis because of lack of published data in the Canadian population. Hence, the burden of AOM in Canada may have been underestimated in this study.
Conclusions PHiD-CV may offer substantial benefits in terms of reduced ambulatory visits, antibiotic prescriptions and hospitalizations for AOM compared to PCV-7 and PCV-13, translating into better quality of life for children and substantial cost-savings to the Canadian healthcare system and society.