1. Plans to Assess the Effectiveness of Seasonal and Pandemic Influenza Vaccines during 2009-10 David Shay MD, MPH (Prevention Assessment and Modeling Team Lead), Influenza Division Presented by Anthony Fiore MD, MPH Epidemiology and Prevention Branch Influenza Division, NCIRD, CDC Vaccines and Related Biological Products Advisory Committee Meeting July 23, 2009

2. Background/Assumptions Pandemic H1N1 vaccine purchased by USG Estimate that 50+ million doses of monovalent vaccine available for distribution by 15 October Regular seasonal vaccine campaign and pandemic vaccine program 2 doses of monovalent pandemic vaccine offered

3. Information requirements Is illness prevented by pandemic vaccine(s)? Does clinical vaccine effectiveness (VE) differ for receipt of 1 vs. 2 doses? Does VE vary by age, presence of underlying illness, or vaccine type? Does VE vary by outcome measured (e.g., symptomatic illness, medically attended acute respiratory illness, hospitalization)? Rapid VE assessment required for some outcomes Need to weigh absolute vaccine benefits vs. risks for potential adverse events

4. VE for lab-confirmed outcomes CDC plans to use lab-confirmed influenza outcomes whenever feasible, to improve the validity and comparability of VE estimates Sensitivity and particularly specificity of clinical outcomes is fairly low, and –Specificity varies by age group –Specificity varies during the course of an outbreak Need to estimate VE for nH1N1 and seasonal influenza Leverage platforms developed over past 5 seasons for seasonal VE to estimate pandemic VE as well

5. VE assessment methods VE for prevention of RT-PCR confirmed medically attended influenza in 4 community-based sites: Marshfield, Michigan, Rochester, and Vanderbilt (MMRV) VE for prevention of influenza hospitalizations as diagnosed by provider-ordered clinically available tests in 10 Emerging Infections Program (EIP) sites Early assessments of VE among health care workers and others at high priority for receipt of vaccine Simple VE assessments by screening method; for example, effectiveness of seasonal vaccine for nH1N1

6. Community assessments (MMRV) Cases: patients seeking medical care for acute respiratory illness who consent and test positive for influenza by CDC rRT-PCR methods Comparison group: those who seek care for acute respiratory illness, but test negative for influenza Vaccination data collected by self-report and record review System developed to make interim and final VE estimates each season Similar methods will be used to assess VE for seasonal and pandemic vaccines in 2009-10

7. EIP studies Cases are hospitalized patients in 10 EIP sites (14% of US population) who test positive for influenza by clinical tests; for this coming season, we will use CDC rRT-PCR methods Controls are age- and community-matched persons who are not hospitalized with an acute respiratory illness up to the date of admission of the corresponding case Case and control interviews and medical record reviews First study of VE for lab-confirmed hospitalizations among young children conducted 2005-06 through 2007-08 seasons; first for similar outcome among older adults started during 2008-09 season Large catchment area is strength of EIP system, permitting VE assessments for the more severe outcomes (hospitalization)

8. Studies to address other needs VE among those who receive vaccine first –Conduct assessments among health care workers –Coordinate methods for VE studies with DoD for both pandemic and seasonal influenza Special studies among those at particular risk –VE among pregnant women and their newborns

9. Summary Variety of methods will be used by CDC to provide estimates of VE Monitoring for novel H1N1 infections continues at 4 community VE sites Challenges to rapidly assessing VE –Number of possible circulating strains –Use of multiple vaccines

10. Thanks Investigators at Marshfield Clinic, Univ of Michigan, Univ of Rochester, and Vanderbilt Univ EIP investigators Paul Garguillo Leslie Sokolow Jeff Chen Jill Ferdinands Laurie Kamimoto Ben Silk nH1N1 investigation teams