1. ENHANCED SURVEILLANCE OF NOVEL H1N1 VACCINES AMONG MILITARY PERSONNEL VRBPAC Meeting LTC Patrick Garman, PharmD, PhD Deputy Director for Scientific Affairs Military Vaccine Agency 18 November 2009 UNCLASSIFIED

2. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 BOTTOM LINE to accomplish the mission. Everything we do, every system we adopt, and every medical intervention we make, serves one purpose; to get these Soldiers to the fight with everything we can provide them to accomplish the mission. UNCLASSIFIED

3. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Overview Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel - (2 Nov Start date) Case Verification Working Group Novel H1N1 Vaccine in Pregnancy

4. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel OBJECTIVES To conduct weekly enhanced surveillance of H1N1 vaccine safety in near real-time on pre-specified high priority outcomes of interest among military personnel vaccinated with H1N1 vaccine(s) during the 2009-2010 H1N1 vaccination period. To perform data mining of other diagnosis codes/groups following administration of H1N1 vaccine(s) on a monthly basis among military personnel. To conduct comprehensive analyses of possible associations between H1N1 vaccine and adverse events after immunization program is completed.

5. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Data Source. The Defense Medical Surveillance System (DMSS) is a centralized electronic query database developed by the Armed Forces Health Surveillance Center (AFHSC). The DMSS contains both current and historical data on diseases, medical events, vaccination history, demographics, Service (Army, Air Force, Navy, Marine Corps, and Coast Guard), and deployment status for the U.S. military personnel since 1990. It includes both inpatient and outpatient (including emergency room (ER)) data. Contains ~1.4 million active records per year. Population. The surveillance population will include Service members between 17 and 64 years of age who are vaccinated with H1N1 monovalent vaccine during the H1N1 vaccination period. Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel

6. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 DMSS Queries. Aggregate data from the DMSS are generated weekly and include: Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel - Age / age group - Gender - Week of H1N1 immunization, - Type of immunization - Type of potential adverse event (AE) - Number of days between H1N1 administration and the potential AE - Concurrent vaccines - Medical setting where the potential AE was diagnosed (such as inpatient or outpatient)

7. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Disease/ Disease CategoryICD-9-CM CodePost-vacc F/U Period Guillain-Barré Syndrome (GBS)42 days Guillain-Barré Syndrome (GBS)357.0 Optic neuritis42 days Optic neuritis, unspecified377.30 Optic papillitis377.31 Retrobulbar neuritis377.32 Toxic optic neuropathy377.34 Optic neuritis, other377.39 Pre-specified High Priority Outcomes of Interest

8. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Disease/ Disease CategoryICD-9-CM CodePost-vacc F/U Period Neurologic Outcomes21 days and 42 days Encephalitis, myelitis, and encephalomyelitis following immunization procedures323.5 Encephalitis and encephalomyelitis following immunization procedures323.51 Myelitis following immunization procedures323.52 Postinfectious encephalitis, myelitis, and encephalomyelitis323.6 Infectious acute disseminated encephalomyelitis (ADEM) (includes acute necrotizing hemorrhagic encephalopathy) 323.61 Other postinfectious encephalitis and encephalomyelitis323.62 Postinfectious myelitis323.63 Other causes of encephalitis, myelitis, and encephalomyelitis (includes noninfectious ADEM) 323.8 Other causes of encephalitis and encephalomyelitis (includes noninfectious ADEM) 323.81 Other causes of myelitis (includes transverse myelitis NOS)323.82 Unspecified cause of encephalitis, myelitis, and encephalomyelitis323.9 Acute transverse myelitis341.2 Pre-specified High Priority Outcomes of Interest

9. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Disease/ Disease CategoryICD-9-CM CodePost-vacc F/U Period Bell's palsy42 days and 60 days Bell's palsy351.0 Facial weakness/facial droop781.94 Anaphylaxis <48 hrs Other anaphylactic shock995.0 Anaphylactic reaction to serum999.4 Idiopathic thrombocytopenic purpura 42 days Idiopathic thrombocytopenic purpura287.31 Secondary thrombocytopenia287.4 Thrombocytopenia, unspecified287.5 Pre-specified High Priority Outcomes of Interest

10. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel Analysis. Rapid Cycle Analysis (RCA) will be performed on the aggregated weekly H1N1 vaccine safety data by CDC/VSD. Analytic methods: a. Comparison to background rates using Poisson regression maxSPRT. (Have weekly data from 2004-08 for comparison) b. When applicable a secondary analysis using self-controlled case series.

11. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 First shipment of H1N1 vaccine arrives in Central Command’s AOR

12. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Over 30,000 vaccinations administered to Military personnel. No high priority outcomes of interest. Initial military vaccinees have not reached end of risk windows. Over 500,000 doses distributed within DoD. Vaccine is being administered to deployed Service members throughout the world (Iraq, Afghanistan, S. Korea, Europe, etc.). Service members receiving mainly inactivated multi-dose Novartis vaccine. Vaccine is being administered to DoD beneficiaries living overseas and in the US. Significant increases in doses administered over next three weeks. End State: Vaccinate close to three million Service members (Active Duty, Guard, and Reserve, Coast Guard). Overview Two Weeks and Counting

13. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Data mining. To identify possible unexpected adverse events following novel H1N1 vaccination, we will conduct surveillance of all 3-digit ICD-9-CM codes occurring in the primary diagnostic position excluding certain conditions surrounding pregnancy and the perinatal period. The surveillance risk window is 60 days following vaccination. The comparison group will be individuals who received the 2008-2009 seasonal inactivated influenza vaccine. We will calculate incidence rate ratios (IRR) and 95% confidence intervals (CI) adjusted for age and gender. Outcomes with an IRR and 95% CI greater than 1.0 will be assessed for biologic plausibility. If plausible, additional analyses and validation will be conducted to determine if they are true adverse events. Enhanced Surveillance of Novel H1N1 Vaccine among Military Personnel

14. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 DoD Case Verification Working Group Aysha Akhtar, M.D., FDA, Analytical Epidemiology Branch (Office of Biostatistics and Epidemiology) COL Matthew P. Wicklund, M.D., USAF COL David Bartoszek, M.D., USA LCDR Craig Carroll, M.D., USN Limone Collins, M.D., DoD Jay Montgomery, M.D., DoD Alan Ou, M.D. FDA, Analytical Epidemiology Branch (Office of Biostatistics and Epidemiology) Working Group of FDA and DoD Neurologists and Immunologists – Meet as needed to review and verify potential high priority AEs

15. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Novel H1N1 Vaccine in Pregnancy Primary Objective: To describe the incidence and prevalence of adverse reproductive health outcomes among female military service members who received the novel H1N1 vaccine in pregnancy. Principal Investigator: Tyler C. Smith, MS, PhD Director, Deployment Health Research, Naval Health Research Center, San Diego, CA

16. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Novel Influenza A (H1N1) Vaccine in Pregnancy Secondary objectives: –To determine if H1N1 vaccination in pregnancy or periconceptually is independently associated with pregnancy loss, fetal death, preeclampsia, or preterm labor. –To determine if H1N1 vaccination in pregnancy or periconceptually is independently associated with preterm birth, in utero growth problems, birth defects, or a decreased male:female sex ratio among infants born to active duty military women who received the vaccine. –To describe the 2009-2010 DoD H1N1 vaccination campaign as it pertains to active duty military women who were vaccinated during or shortly before pregnancy.

17. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Novel Influenza A (H1N1) Vaccine in Pregnancy Each objective will be carried out both on an ongoing basis during the 2009- 2010 H1N1 vaccination period and at the completion of the first year of life of all of the infants born to H1N1-vaccinated military women. For objective two, growth problems in infancy and birth defects diagnosed through the first year of life will be evaluated in the analysis that includes the infants’ first year of life (“completion analysis”). Study is waiting final IRB approval

18. LTC Patrick Garman (703)681-5101 patrick.garman@us.army.milVRBPAC 18 November 09 Acknowledgements DoD Organizations: –Armed Forces Health Surveillance Center –Military Vaccine Agency –Vaccine Healthcare Centers Project collaborators/Co-investigators –FDA/CBER - Office of Biostatistics and Epidemiology (Analytic Epidemiology Branch) –CDC – Immunization Safety Office Facilitator: –National Vaccine Program Office