the importance of quality outcomes data: expected cost effectiveness of high-dose trivalent...
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The Importance of Quality Outcomes Data:
Expected Cost Effectiveness of High-Dose Trivalent Inactivated
Influenza Vaccine (HD-IIV3) in US Seniors
Ayman Chit, M.Biotech, PhD
Director, Health Outcomes and Economics, North America
Conflict of Interest
●I am a current employee of Sanofi Pasteur and past employee of GlaxoSmithKline
●Both companies are influenza vaccine manufacturers
●I own stock in both companies
●This study was funded by Sanofi Pasteur
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Standard-Dose Trivalent Inactivated Influenza Vaccine (SD-IIV3) Effectiveness by Age1
Reference: 1. Monto AS, Ansaldi F, Aspinall R, et al. Influenza control in the 21st century: optimizing protection of older adults. Vaccine. 2009;27:5043-5053.
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High Dose (HD-IIV3) is Superior to Standard-Dose (SD-IIV3) Trivalent Inactivated Influenza Vaccine
●FIM12 efficacy trial (>30,000 older adults) met its primary endpoint for superior efficacy
●HD-IIV3 was 24.2% more effective than SD-IIV3 in preventing lab confirmed influenza in adults ≥65 years of age
●Effectiveness assessments suggest benefits for the prevention of: ● Hospitalization ● Pneumonia ● Other cardio-respiratory events
●FIM12 also reaffirmed the safety of HD-IIV3 vaccine as demonstrated in previous studies.
Reference: Greenberg D. ACIP 24 October 2013 Meeting. http://www.cdc.gov/vaccines/acip/meetings/downloads/slides-oct-2013/04-Fluzone-Greenberg.pdf
Study Objective
●Given the various vaccine options available to US seniors we modeled each vaccine’s expected: ●Public health impact●Budget impact●Cost-utility
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Model Overview
● Interventions● High-dose trivalent inactivated influenza vaccine (HD-IIV3)● Standard dose trivalent inactivated influenza vaccine (SD-IIV3)● Standard dose quadrivalent inactivated influenza vaccine (SD-IIV4) ● No vaccination
● Model structure● Stochastic and static model that does not consider herd effects● 1 influenza season reflecting epidemiology from previous decade● Societal perspective
● Outcomes● Symptomatic influenza● Hospitalized influenza● Influenza-related death● Productivity● Quality of life
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Model Inputs
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●Disease outcome rates● Influenza attack rate obtained from placebo arms of RCTs1,2,3
● Influenza-related hospitalizations and mortality rates obtained from CDC publications4,5
●Monetary costs●Health care costs obtained from Centers for Medicare & Medicaid
Services (CMS) data●Vaccine prices obtained from Medicare price lists
●Vaccine efficacy●SD-IIV3 efficacy obtained from published meta-analysis6
●SD-IIV4 efficacy estimated based on modified CDC methodology7
●HD-IIV3 relative efficacy obtained from FIM12 clinical trialReferences1.Govaert TM, Thijs CT, Masurel N, Sprenger MJ, Dinant GJ, Knottnerus JA. JAMA 1994; 272(21):1661-1665.2.Edmondson WP, Jr., Rothenberg R, White PW, Gwaltney JM, Jr. Am J Epidemiol 1971; 93(6):480-486.3.Rudenko LG, Arden NH, Grigorieva E, Naychin A, Rekstin A, Klimov AI et al. Vaccine 2000; 19(2-3):308-318.4.Zhou H, Thompson WW, Viboud CG, Ringholz CM, Cheng PY, Steiner C et al. Clin Infect Dis 2012; 54(10):1427-14365.MMWR, 20106.Beyer WE, McElhaney J, Smith DJ, Monto AS, Nguyen-Van-Tam JS, Osterhaus AD. Vaccine 2013; 31(50):6030-6033.7.Reed C, Meltzer MI, Finelli L, Fiore A. Vaccine 2012; 30(11):1993-1998
Impact on Health Outcomes
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Outcomes SD-IIV3 SD-IIV4 HD-IIV3HD-IIV3 vs. SD-IIV3
HD-IIV3vs. SD-IIV4
Total number of cases 1,589,134 1,562,433 1,393,177 -195,958 -169,257
Total number of outpatient consultations
1,118,433 1,099,641 980,518 -137,915 -119,123
Total number of hospitalizations
122,598 121,253 100,031 -22,567 -21,222
Total number of deaths 29,460 29,249 24,037 -5,423 -5,212
Total number of workdays lost
675,992 665,629 582,253 -93,739 -83,377
Total number of QALYs 205,980,642 205,981,947 206,009,666 29,023 27,718
HD-IIV3 is expected to provide the highest public health benefit
Outcomes prevented at the level of the entire US senior populationAssuming 67% vaccine uptake rate in the HD-IIV3, SD-IIV4 and SD-IIV3 groups
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Impact on Costs
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Category SD-IIV3 (USD) SD-IIV4 (USD) HD-IIV3 (USD)HD-IIV3 vs. SD-IIV3 (USD)
HD-IIV3 vs. SD-IIV4 (USD)
Vaccination 1,063,695,015 1,258,914,335 1,631,833,294 568,138,279 372,918,958
Primary care 134,704,053 132,440,714 118,093,561 -16,610,492 -14,347,154
Hospitalization 1,532,600,817 1,515,778,240 1,250,484,707 -282,116,109 -265,295,501
Productivity 195,767,366 192,766,281 168,620,448 -27,146,918 -24,145,896
Total 2,926,767,251 3,099,899,570 3,169,032,010 242,264,760 69,130,407
Increased expenditures on HD-IIV3 expected to be partly offset by reduced health services consumption and increased productivity
Costs at the level of the entire US senior populationAssuming 67% vaccine uptake rate in the HD-IIV3, SD-IIV4 and SD-IIV3 groups
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Cost-Utility Analysis
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Perspective Incremental cost-utility ratios (USD/QALY)
HD-IIV3 vs. SD-IIV3 HD-IIV3 vs. SD-IIV4
Societal 8,347 2,494
Third Party Payer 10,350 4,365
HD-IIV3 is a cost-effective alternative to SD-IIV3 and SD-IIV4
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Probabilistic Sensitivity Analyses: HD-IIV3 vs. SD-IIV3
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• 70.6% of simulations ≤ $100,000/QALY
• 59.7% of simulations ≤ $50,000/QALY
• HD-IIV3 dominates SD-IIV3 in 19.3% of simulations
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Trivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Deterministic Sensitivity Analyses: HD-IIV3 vs. SD-IIV3
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Most influential variables were:
•influenza-related death and hospitalization•relative vaccine efficacy (RVE) of HD-IIV3 against hospitalization and death
Influential Variables
HD-IIV3 is expected to dominate SD-IIV3 and SD-IIV4 during severe influenza seasons
Even during unusually mild influenza seasons, the vaccine is expected to be cost effective
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Two-way sensitivity analysis on the two most influential variables: influenza-related hospitalization and death rates
Incremental cost effectiveness ratio (USD/QALY)
HD-IIV3 vs. SD-IIV3 HD-IIV3 vs. SD-IIV4
Base-case influenza season
8,347 2,494
Low severity season 78,899 37,430
High severity season HD-IIV3 dominant HD-IIV3 dominant
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Limitations
●Vaccine efficacy estimates:● No direct data are available on the efficacy of SD-IIV4 in seniors● Data on the efficacy of SD-IIV3 in preventing hospitalizations and
death was derived from non randomized studies● No direct data on relative efficacy of HD-IIV3 in preventing death
● Indirect benefits of the vaccines were excluded
● Impact of influenza vaccination on reducing disability in the seniors was not included
14HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard Dose Quadrivalent Inactivated Influenza Vaccine
Conclusions
●HD-IIV3 is expected to achieve significant reductions in influenza-related morbidity and mortality compared to SD-IIV3 and SD-IIV4
●HD-IIV3 is a cost-effective alternative to both SD-IIV3 and SD-IIV4 in seniors
●ICERs where highly influenced by rates of serious influenza complications (hospitalization and death)
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard Dose Quadrivalent Inactivated Influenza Vaccine
Thank You
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Model Structure
Deterministic Sensitivity Analyses: HD-IIV3 vs. SD-IIV4
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Most influential variables were:
•influenza-related death and hospitalization•relative vaccine efficacy (RVE) of HD-IIV3 against hospitalization
Probabilistic Sensitivity Analysis: HD-IIV3 vs. SD-IIV4
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• 81.9% of simulations ≤ $100,000/QALY
• 70.3% of simulations ≤ $50,000/QALY
• HD-IIV3 dominates SD-IIV4 in 34.4% of simulations
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year
Cost-Utility Analysis
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HD-IIV3 is a more efficient use of resources than SD-IIV3 and SD-IIV4
Cost-Effectiveness Frontier
$17,325/QALY
$13,660/QALY
$11,460/QALY
HD-IIV3: High-Dose Trivalent Inactivated Influenza VaccineSD-IIV3: Standard-Dose Trivalent Inactivated Influenza VaccineSD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza VaccineQALY: Quality-Adjusted Life Year