1. Influenza Vaccine Program Effectiveness in the United States
National Immunization Conference March Joseph Bresee Influenza Division

2. 2010: 50th Anniversary of First Influenza Vaccine Recommendation
Burney LE. Public Health Rep Oct;75(10):944 1

3. Influenza vaccination recommendations over time
Before 2000: Persons aged 65 or older
Persons with high-risk chronic medical conditions
Pregnant women in the second or third trimester
Household contacts of the above
Health care workers
2000: Adults 50 and older
2004: Children aged 6—23 months
Household contact of children aged months
Women who will be pregnant during influenza season
2006: Children aged 6—59 months
Household contacts of children aged 0—59 months
2008: All children aged 6 months—18 years
2010: All persons > 6 months in the US

4. During the last decade…
More people getting vaccinated with influenza vaccines
Greater use of vaccines in persons at high risk of complications
More awareness of the need for vaccination
Some skepticism of the value of influenza vaccination
Are influenza vaccines effective in preventing influenza- associated illnesses each year?

5. New Vaccine Surv. Network Emerging Infections Program
Influenza Division program to measure influenza vaccine effectiveness in the U.S.
New Vaccine Surv. Network
6 – 59 mo.
OP, Hosp.
Emerging Infections Program
6 – 23 m
Hosp.
6–59m
Hosp.
Adults >18 y Hosp.
Adults > 50 y Hosp.
Marshfield Clinic
ACIP recommended groups
MAARI
US VE Network - 1
ACIP recommended groups - MAARI
Special studies
HCWs, Peds. ICU, Pregnant
US VE Network - 2
All Ages
MAARI
03-04
05-06
07-08
09-10
11-12

6. During the last decade…
More people getting vaccinated with influenza vaccines
Greater use of vaccines in persons at high risk of complications
More awareness of the need for vaccination
Some skepticism of the value of influenza vaccination
Are influenza vaccines in preventing influenza-associated illnesses each year? Yes. …but the effectiveness of vaccines vary by season, population, and outcome measured

7. And, communication of influenza vaccine effectiveness is difficult

8. Influenza Vaccine Program Effectiveness Project
Question: Are influenza vaccine programs effective in reducing influenza-associated health outcomes?
Goal: Estimate the number of averted influenza-associated outcomes that result from influenza vaccination?
Advantages:
Uses data that are collected as core program activities (Influenza Division and Immunization Services Division)
Illness/outcomes averted may be an easier and more meaningful way to communicate the value of the vaccine?
Estimates can be updated annually
Can apply economic values to the model; estimate effect of program changes, etc.

9. Project Phases
Phase 1: Develop the model Phase 2: Apply the model to previous years’ data ( ) Phase 3: Run the model following each influenza season to estimate the effect of vaccination annually Phase 4: Apply economic data to the model to estimate costs/costs averted Use the model to address programmatic questions (e.g. value of new vaccines vs. existing vaccines)

10. Influenza Vaccine Program Effectiveness Project Steps to estimate vaccine impact
Estimate observed annual burden of influenza-associated outcomes
Estimate observed risk of influenza-associated outcomes among susceptible individuals
Using data on annual vaccine coverage and vaccine effectiveness
Calculate expected burden of influenza-associated outcomes in population with no vaccination
Calculate difference in outcomes attributable to vaccination program

11. 1. Estimating annual US burden of influenza
Outcomes
Illness
Medically-attended illness
Hospitalization

12. 1. Estimating annual US burden of influenza: Framework
020502Ac-ADIP_Rota-WOR008STO
Laboratory-confirmed cases in EIP represent a fraction of true hospitalized cases
Not everyone tested for influenza
Test sensitivity varies
Multiplier = 2.7 ( )
Each laboratory-confirmed hospitalization represents
2.7 total influenza-associated hospitalizations
Source: Reed et al. EID, 2009
1. Estimating annual US burden of influenza: Framework
2. Extrapolate to the US population
Reported rate hospitalization in EIP influenza surveillance
Expected rate hospitalization
Estimated Hospitalizations
1. Correct for under- detection
Shrestha et al. CID 2011; Reed et al. EID, 2009

13. 1. Estimating annual US burden of influenza: Framework
020502Ac-ADIP_Rota-WOR008STO
Number of cases of illness estimated in the community per hospitalized case
Reflects the risk of hospitalization among persons ill with influenza
Stratified by age group:
6 mos–4 yrs = 143
5–19 yrs = 364
20–64 yrs = 148
65+ yrs = 64
Source: Reed, et al. EID, 2009.
1. Estimating annual US burden of influenza: Framework
Reported rate hospitalization in EIP influenza surveillance
Expected rate hospitalization
Estimated Hospitalizations
3. Ratio cases to hospitalizations
Estimated Cases
Shrestha et al. CID 2011; Reed et al. EID, 2009

14. 1. Estimating annual US burden of influenza: Framework
020502Ac-ADIP_Rota-WOR008STO
Probability of seeking medical attention if ill with influenza
Source: BRFSS Influenza-like illness (ILI) module
: 42% of persons with ILI reported seeking medical care for their illness
Example: 2005–06, 6 mos–4 yrs:
2,016,840 influenza illnesses
x 42% of ill persons seek medical care
= 847,043 medically-attended influenza illnesses
1. Estimating annual US burden of influenza: Framework
Reported rate hospitalization in EIP influenza surveillance
Expected rate hospitalization
Estimated Hospitalizations
Estimated Cases
4. Care-seeking fraction
Estimated Medically-attended Cases
Shrestha et al. CID 2011;
Reed et al. EID, 2009

15. 2. Risk of influenza outcomes if susceptible
Influenza-related outcomes occurred among persons at risk for influenza
= No. of influenza-related outcomes / population at risk
Population at risk = population not protected from effective vaccination or having prior illness
Effective vaccination = VE x VC
Stratified by month and age group
6 mos–4 yrs; 5–19 yrs; 20–64 yrs; 65+ yrs

16. Example: Population at risk
Month
iVC* VE
Est. Illness
Pop at risk
September
15%
60%
= 1000*(1-60%*15%)
= 910
October
10% 5
= (910-0)*(1-60%*10%)
= 855
November 5% 10
= (855-5)*(1-60%*5%)
= 825
December 20
= (825-10)*(1-60%*5%)
= 790
January 2% 40
= (790-20)*(1-60%*2%)
= 761
Etc…
Total = 75
* Incremental vaccine coverage = additional vaccination during that month (averaged across the month)

17. Example: Risk of outcomes among susceptibles
Month
Pop at Risk
Est. illnesses
Risk of illness
September
910
0/910 = 0%
October
855 5
5/855 = 0.6%
November
825 10
10/825 = 1.2%
December
790 20
20/790 = 2.5%
January
761 40
40/761 = 5.3%
Etc…

18. 3. Estimated burden without vaccination
Apply risk of outcome among susceptibles to population susceptible without vaccination
Remove prior illness each month, but no longer remove persons vaccinated

19. Example: Estimated burden without vaccination
Month
Risk of illness
Pop at risk
(without vaccination)
Expected Illnesses
September 0%
1000
=1000 * 0% = 0
October
0.6%
= = 1000
= 1000 * 0.6% = 6
November
1.2%
= = 994
=994 * 1.2% = 12
December
2.5%
= = 982
=982 * 2.5% = 25
January
5.3%
= = 957
= 957 * 5.3% = 50
Etc…
Total = 93

20. 4. Calculate net impact of vaccination program
Difference between expected outcomes without vaccination and estimated annual burden
Using the illness example presented earlier:
93 expected without vaccination – 75 observed
18 averted illnesses

21. Draft Results: Averted illnesses
Year
All ages
0-4 yrs
5-19 yrs
20-64 yrs
65+ yrs
1,676,572
310,151
218,688
345,959
801,774
841,009
241,702
155,759
213,604
229,944
2,222,375
298,229
263,028
624,824
1,036,295
1,525,421
406,983
462,155
416,375
239,908
5,191,539
901,538
1,218,107
1,768,658
1,303,236
Five Season Total
11,456,915
2,158,601
2,317,738
3,369,421
3,611,156

22. Draft Results: Averted medically-attended illness
Year
All ages
0-4 yrs
5-19 yrs
20-64 yrs
65+ yrs
704,160
130,263
91,849
145,303
336,745
369,335
101,515
65,419
89,714
112,688
933,397
125,256
110,472
262,426
435,244
657,748
170,933
194,105
174,878
117,833
2,180,446
378,646
511,605
742,837
547,359
Five Season Total
4,845,087
906,613
973,450
1,415,157
1,549,868

23. Draft Results: Averted hospitalizations
Year
All ages
0-4 yrs
5-19 yrs
20-64 yrs
65+ yrs
17,494
2,162
600
2,334
12,398
7,702
1,685
427
1,441
4,149
23,041
2,079
721
4,216
16,024
11,252
2,837
1,267
2,810
4,338
41,711
6,285
3,340
11,934
20,152
Five Season Total
101,201
15,049
6,355
22,736
57,061

24. Summary
Substantial annual averted disease burden from influenza vaccination program, but varies by
season and by age group
due to variability in VC, VE, annual disease burden
Having a standardized framework to evaluate program impact
allows for comparison across seasons to examine the impact of changes in burden, VE, and VC
helps identify and prioritize data needs to evaluate program impact on a routine basis
Program improvements will me made by
increasing coverage in non-elderly persons
improving effectiveness of vaccines in elderly persons

25. Influenza Vaccine Program Effectiveness Team
Deliana Kostova Carrie Reed Po-Yung Cheng Martin Meltzer Paul Gargiullo David Shay Lyn Finelli Jim Singleton Joe Bresee