Influenza Vaccine Program Effectiveness in the United States National Immunization Conference March 2012 Joseph Bresee Influenza Division

2010: 50th Anniversary of First Influenza Vaccine Recommendation Burney LE. Public Health Rep. 1960 Oct;75(10):944 1

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 0--23 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

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?

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

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

And, communication of influenza vaccine effectiveness is difficult

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.

Project Phases Phase 1: Develop the model Phase 2: Apply the model to previous years’ data (2005-2010) 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)

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

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

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 (1.7-4.5) 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

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

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 2006-07: 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

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

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)

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…

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

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% = 1000-0 = 1000 = 1000 * 0.6% = 6 November 1.2% = 1000-6 = 994 =994 * 1.2% = 12 December 2.5% = 994-12 = 982 =982 * 2.5% = 25 January 5.3% = 982-25 = 957 = 957 * 5.3% = 50 Etc… Total = 93

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

Draft Results: Averted illnesses Year All ages 0-4 yrs 5-19 yrs 20-64 yrs 65+ yrs 2005-06 1,676,572 310,151 218,688 345,959 801,774 2006-07 841,009 241,702 155,759 213,604 229,944 2007-08 2,222,375 298,229 263,028 624,824 1,036,295 2008-09 1,525,421 406,983 462,155 416,375 239,908 2010-11 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

Draft Results: Averted medically-attended illness Year All ages 0-4 yrs 5-19 yrs 20-64 yrs 65+ yrs 2005-06 704,160 130,263 91,849 145,303 336,745 2006-07 369,335 101,515 65,419 89,714 112,688 2007-08 933,397 125,256 110,472 262,426 435,244 2008-09 657,748 170,933 194,105 174,878 117,833 2010-11 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

Draft Results: Averted hospitalizations Year All ages 0-4 yrs 5-19 yrs 20-64 yrs 65+ yrs 2005-06 17,494 2,162 600 2,334 12,398 2006-07 7,702 1,685 427 1,441 4,149 2007-08 23,041 2,079 721 4,216 16,024 2008-09 11,252 2,837 1,267 2,810 4,338 2010-11 41,711 6,285 3,340 11,934 20,152 Five Season Total 101,201 15,049 6,355 22,736 57,061

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

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