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
2
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 (SDIIV3) Trivalent Inactivated Influenza Vaccine
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●
●
●
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
5
Model Overview
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●
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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
6
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 trial
References
1. 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):1427-1436
5. MMWR, 2010
6. 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
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Impact on Health Outcomes
Outcomes
SD-IIV3
SD-IIV4
HD-IIV3
HD-IIV3
HD-IIV3
vs. SD-IIV3 vs. 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
Outcomes prevented at the level of the entire US senior population
Assuming 67% vaccine uptake rate in the HD-IIV3, SD-IIV4 and SD-IIV3 groups
HD-IIV3 is expected to provide the highest public health benefit
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
8
Impact on Costs
Category
Vaccination
Primary care
Hospitalization
Productivity
Total
SD-IIV3 (USD)
SD-IIV4 (USD)
HD-IIV3 (USD)
HD-IIV3 vs.
SD-IIV3 (USD)
HD-IIV3 vs.
SD-IIV4 (USD)
1,063,695,015
1,258,914,335
1,631,833,294
568,138,279
372,918,958
134,704,053
132,440,714
118,093,561
-16,610,492
-14,347,154
1,532,600,817
1,515,778,240
1,250,484,707
-282,116,109
-265,295,501
195,767,366
192,766,281
168,620,448
-27,146,918
-24,145,896
2,926,767,251
3,099,899,570
3,169,032,010
242,264,760
69,130,407
Costs at the level of the entire US senior population
Assuming 67% vaccine uptake rate in the HD-IIV3, SD-IIV4 and SD-IIV3 groups
Increased expenditures on HD-IIV3 expected to be partly offset by
reduced health services consumption and increased productivity
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
9
Cost-Utility Analysis
Perspective
Incremental cost-utility ratios (USD/QALY)
Societal
Third Party Payer
HD-IIV3 vs. SD-IIV3
HD-IIV3 vs. SD-IIV4
8,347
2,494
10,350
4,365
HD-IIV3 is a cost-effective alternative to SD-IIV3 and
SD-IIV4
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
10
Probability of HD cost-effective to IIV3
Probabilistic Sensitivity Analyses:
HD-IIV3 vs. SD-IIV3
1
0.9
0.8
0.706
0.7
0.6
0.597
0.5
0.4
• 70.6% of simulations ≤ $100,000/QALY
0.3
• 59.7% of simulations ≤ $50,000/QALY
0.2
0.1
• HD-IIV3 dominates SD-IIV3 in 19.3% of
simulations
0
Willingness-to-pay (USD/QALY)
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Trivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
11
Deterministic Sensitivity Analyses:
HD-IIV3 vs. SD-IIV3
529
Excess death rate [121.1-8/100,000]
47,506
Dominant
Excess hospitalization rate [1,108-186/100,000]
12,175
5,644
Fluzone HD RVE against death [47-10%]
Fluzone HD RVE against hospitalization [47-10%] 3,148
7,128
Attack rate [10-1%]
IIV3 cost [$13.0810.69]
7,686
Fluzone HD RVE against influenza [36.52-9.69%]
7,517
Discount rate [0-5%]
7,414
7,305
Workdays lost per case [5-0.5]
IIV3 VE against hospitalization [10-50%]
Hospitalization costs HR [$13,728-11,703]
7,700
7,771
Duration of influenza symptoms [11.5-3.7]
7,917
IIV3 VE against death [10-50%]
8,080
IIV3 VE against influenza [33-62%]
8,055
8,159
Hospitalization costs LR [$12,817-11,010]
Utility uncomplicated influenza [0-0.25]
22,477
15,276
9,811
9,976
9,398
8,957
8,821
9,139
8,924
8,541
8,699
8,589
Most influential variables were:
8,535
8,347
•
•
Probability of going to GP given Influenza HR [63.8-100%]
8,122
8,286
Outpatient cost per case [$101-119]
8,314
8,401
Probability of going to GP given Influenza LR [56.4-67.3%]
8,322
Utility complicated influenza [0-0.25]
8,311
8,330
8,372
8,356
Proportion of high risk [39.3-44.5%]
0
GP: General Practitioner
HD: High-Dose Vaccine
HR: High risk
IIV3: Trivalent Influenza Vaccine
LR: Low risk
8,409
influenza-related death and hospitalization
relative vaccine efficacy (RVE) of HD-IIV3
against hospitalization and death
8,365
10,000
20,000
30,000
Incremental cost-utility ratio (USD/QALY)
QALY: Quality-Adjusted Life Year
VE: Vaccine efficacy
RVE: Relative vaccine efficacy
VE: Vaccine efficacy
40,000
50,000
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Influential Variables
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 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
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
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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
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard Dose Quadrivalent Inactivated Influenza Vaccine
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Conclusions
● HD-IIV3 is expected to achieve significant reductions in
influenza-related morbidity and mortality compared to SDIIV3 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 Vaccine
SD-IIV3: Standard Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard Dose Quadrivalent Inactivated Influenza Vaccine
Thank You
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Model Structure
|
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Deterministic Sensitivity Analyses:
HD-IIV3 vs. SD-IIV4
Dominant
Excess hospitalization rate [1,108-186/100,000]
Excess death rate [121.1-8/100,000]
Fluzone HD RVE against hospitalization [47-10%]
6,235
14,628
157
Dominant
9,123
IIV4 VE against hospitalization [10-60%]
6,819
Fluzone HD RVE against death [47-10%]
1,639
IIV4 VE against death [10-60%]
6,636
4,218
1,999
1,614
Attack rate [10-1%]
Fluzone HD RVE against influenza [36.52-9.69%]
1,690
IIV4 VE against influenza [10-70%]
3,185
2,979
1,535
1,571
Workdays lost per case [5-0.5]
Hospitalization costs HR [$13,728-11,703]
2,913
1,926
Discount rate [0-5%]
3,541
3,062
2,677
Hospitalization costs LR [$12,817-11,010]
2,214
2,309
Duration of influenza symptoms [11.5-3.7]
2,377
Probability of going to GP given Influenza HR [63.8-100%]
2,439
2,550
Outpatient cost per case [$101-119]
2,464
2,543
2,494
Utility uncomplicated influenza [0-0.25]
Probability of going to GP given Influenza LR [56.4-67.3%]
2,433
2,471
Proportion of high risk [39.3-44.5%]
2,478
Utility complicated influenza [0-0.25]
2,483
0
2,000
GP: General Practitioner
HD: High-Dose Vaccine
HR: High risk
IIV4: Quadrivalent Influenza Vaccine
2,679
2,546
2,517
Most influential variables were:
•
•
influenza-related death and hospitalization
relative vaccine efficacy (RVE) of HD-IIV3
against hospitalization
2,511
2,497
4,000
6,000
8,000
10,000
12,000
Incremental cost-utility ratio (USD/QALY)
LR: Low risk
QALY: Quality-Adjusted Life Year
VE: Vaccine efficacy
14,000
16,000
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Probability of HD cost-effective to IIV4
Probabilistic Sensitivity Analysis:
HD-IIV3 vs. SD-IIV4
1
0.9
0.819
0.8
0.7
0.703
0.6
0.5
0.4
0.3
0.2
0.1
• 81.9% of simulations ≤ $100,000/QALY
• 70.3% of simulations ≤ $50,000/QALY
• HD-IIV3 dominates SD-IIV4 in 34.4% of
simulations
0
Willingness-to-pay (USD/QALY)
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
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Cost-Utility Analysis
Cost-Effectiveness Frontier
$11,460/QALY
$30.00
$50,000/QALY
$17,325/QALY
HD-IIV3
SD-IIV4
$25.00
Incremental Cost (USD)
$13,660/QALY
SD-IIV3
$20.00
$15.00
$10.00
$5.00
No Vaccination
$0.00
0
0.0005
0.001
0.0015
0.002
Incremental QALYs
0.0025
0.003
HD-IIV3 is a more efficient use of resources than SD-IIV3 and SD-IIV4
HD-IIV3: High-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV3: Standard-Dose Trivalent Inactivated Influenza Vaccine
SD-IIV4: Standard-Dose Quadrivalent Inactivated Influenza Vaccine
QALY: Quality-Adjusted Life Year
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