1. 1 Preparedness to Monitor Safety of the Pandemic (H1N1) 2009 Vaccines VRBPAC July 23, 2009 Presented by Hector S. Izurieta CBER/FDA

2. Pandemic (H1N1) 2009 Vaccine Potential Issues New strain, monovalent vaccine Potential for use of novel adjuvants Large numbers of vaccinees expected –Most age and risk groups –Relatively rapid vaccine administration Heightened public attention and expectation for robust safety surveillance Expected increase in reporting of temporally-associated events regardless of causal association to vaccination (compared to seasonal vaccine)

3. Adverse Event Monitoring Improvements in passive surveillance (VAERS) for all events (data mining, timeliness of analysis) Enhanced surveillance for pre-specified events identified by: –Pre-licensure safety data –Published literature –Post-licensure safety data with seasonal influenza vaccines –Accruing available international data on pandemic (H1N1) 2009 vaccines with and without adjuvants Need for adaptable toolbox

4. Strategy Enhanced/more timely pharmacovigilance tools for: –Signal detection –Signal strengthening and verification –Confirmation of possible association Increased communication/collaboration among U.S. agencies, and also internationally –Methods –Sharing of preliminary safety surveillance results –Signal validation and confirmation of potential associations

5. Toolbox: Signal Detection ProjectStrengthsPopulationIssues VAERSNear real-time Rare or unexpected events Lot surveillance Data mining Nationwide Passive surveillanc e Not a probability sample of population Underreporting, uneven consistency/completeness of reporting Unknown denominators, no controls Variable reporting biases Stimulated reporting Potential increase in reports: Need for Medical officers for review, improved data mining, immediate signal verification (e.g. observed vs. expected analysis) VAElectronic data on vaccinees Veterans administrati on (VA) personnel Proportion of vaccinees seeking health care in VA system

6. Signal Strengthening, Verification and Confirmation ProjectStrengthsPopulationIssues Vaccine Safety Datalink (CDC/FDA) Near-real time Experienced >9 million, most ages represented, large proportion of children Ascertainment of vaccination: Need vaccine administration data at HMOs (or billing by States) Medicare (CMS-FDA) Near-real time Pilot tested Very large (approximately 38 million elderly) Ascertainment: Providers need to bill Medicare Dept. of Defense/ FDA/CDC First responders Ascertainment of vaccinated cohort Large (>1 million) Healthy population Need to increase capability for real time surveillance through DoD/FDA/CDC collaboration Indian Health Service (HIS) Electronic data, possible ascertainment of vaccinated cohort Large (>1 million) Minority population Need to increase capability for safety surveillance through potential IHS/FDA/CDC collaboration

7. Vaccine Safety Data Link (CDC) Timely Identification and Rapid Assessment Eight managed care organizations representing approximately 9 million US individuals Sequential Analytical methods –Allows rapid assessment of pre-specified adverse events –Simultaneous analysis with appropriate comparison group Requires accurate vaccination information linked to managed care database –Outcome linked with exposure

8. Other CDC Tools for Signal Strengthening and Verification –Emerging Infections Program (EIP) for special studies –Collaboration with the American Academy of Neurology (AAN) Guillain Barre Syndrome (GBS) reporting –Field investigations –Adverse event clinical assessments - CISA (Clinical Immunization Safety Assessment)

9. FDA-CMS Collaboration Development of capability for electronic safety monitoring using Medicare data:Development of capability for electronic safety monitoring using Medicare data: –CMS-FDA pilot project, focused on pandemic preparedness, showed ability to use weekly Medicare data for potential vaccine safety monitoring Example of CBER/CMS collaboration: Rapid analysis of rare adverse event (AE) after flu vaccine in 2006.* Vaccinations AE Cases Per Million

10. DOD-FDA-CDC H1N1 Research Plan Flow Chart Tier-1 AEsTier-2 AEs Retrospective cohorts to estimate background rates Enhanced surveillance through RCA Scan Statistics to confirm the signal Self-controlled case series to verify the signal Retrospective cohorts to estimate incidence rates of AEs during H1N1 vaccination season and to evaluate risk of AE following H1N1 vaccine Bi/Weekly listings of cases and vaccine doses distributed Positive signal Phase 1: Prior to vax Phase 2: During vax Pre-specified AEs Data mining, other analyses Phase 3: Post-vax Positive signal Non-prespecified AEs Positive signal (expert review) Tier-3 AEs

11. Considerations Regarding Vaccine Administration Distribution and administration of vaccines likely to vary by state, city and county –usefulness for safety surveillance will vary Linkage of vaccination data (exposure) to outcome data (medically attended event) is essential to capacity and timeliness for detection/evaluation of safety signals

12. Summary Pandemic preparedness has: –Enhanced capacity for timely signal detection, verification and confirmation –Strengthened collaboration and communication among government agencies and internationally There is variability in data quality and timeliness Timely availability of conclusive post-utilization safety data remains a challenge given: –Expected rapid vaccination period –Questions regarding vaccine distribution and recording –Rarity of expected adverse events

13. Acknowledgements Robert Ball Rickey Wilson Robert Wise Andrea Sutherland Claudia Vellozzi Michael McNeil Douglas Pratt Amy Groom Cunningham Fran Jeff Kelman Patrick Garman Dale Burwen Wei Hua Aysha Akhtar Sukhminder Sandhu Yandong Qiang Laura Polakowski Angela Eick