The Importance of Quality Outcomes Data: Expected Cost Effectiveness of High-Dose Trivalent Inactivated Influenza Vaccine (HD-IIV3) in US Seniors Ayman

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


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


Probabilistic Sensitivity Analyses: HD-IIV3 vs. SD-IIV3

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• 70.6% of simulations ≤ $100,000/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


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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• 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


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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