Overview

1. Monitoring Vaccine Safety during an Influenza PandemicNelson Arboleda, MD, MPH Immunization Safety Office (ISO)Office of the Chief Science officer (OCSO/OD)Centers for Disease Control and Prevention (CDC)

2. Overview • Objectives for vaccine safety monitoring during an influenza pandemic. • Timeline for vaccine safety monitoring. • Existing and Emerging Systems. • 07-08 pilot test of Active Surveillance System. • Project Area (PA) Vaccine Safety Coordinators. • Challenges

3. ObjectivesMonitoring Pandemic Vaccine Safety • Assumption: • Limited/non-existent pre-licensure studies • Vaccination of diverse populations • Fundamental components - Framework • Detection of rare and serious AE. • Assessment of safety profile of pandemic vaccine. • Defining novel non-serious AE. • Ensure vaccine safety during a pandemic. • Continuous Vax Safety monitoring through all phases and waves of Pandemic.

4. Vaccine Safety FrameworkFundamental Components • Acquiring Denominator data • Timeliness of Data • Establishing Linkages with other systems • Risk Communication

5. Safety Monitoring Preparation Period Pre-Pandemic Mon Pandemic Mon

6. Major Vaccine Safety Systems • Existing Surveillance Systems • Vaccine Adverse Event Reporting System (VAERS) • Vaccine Safety Datalink (VSD) • Vaccine Analytic Unit (VAU) • Emerging Surveillance Systems • Active Surveillance System (TeleWatch/IVSS) • National Electronic Injury Surveillance System/Drug Abuse Warning Network (NEISS/DAWN) • Existing Supporting Activities • PA Vaccine Safety Coordinators • CISA (clinical research, risk factor ID) • Brighton collaboration (definitions, Intl Collaboration)

7. Existing System #1: VAERS • VAERS is a national passive surveillance system, allows for the collection and analysis of AE of U.S. licensed vaccines. - Inherent limitations of a passive system. • Existing Survey Capacity: Emergency Preparedness Elective Activity. - Up to 10,000 additional reports per month. - Prepared to fully implement within 10 working days. • New report submission mechanism is critical (PHINMS/HL7). • Enhance new reporting mechanism to decrease processing.

8. S D V Existing System #2: VSD • Collaboration with 8 large MCOs, represents >8.8 million covered lives (3 % of US pop) • Vaccine safety research studies to compare incidence of AE between vaccinated and unvaccinated. - Hypothesis testing • Potential limitations for pandemic safety monitoring: • Timeliness • Coverage – power for Rare AEs. • MCO population limits ability to focus on early priority groups.

9. Planned/Potential VSD Enhancements • Vaccines Distributed outside the MCOs • Estimate background rates for potential AEs. • Conduct ad hoc case control studies. • Identify MCO members who have/will receive vaccine. • Vaccines Distributed within the MCOs • Rapid Cycle Analysis (RCA): Monitor AEs following vaccination in near real-time, so the public can be informed quickly of possible risks (RCA uses data that are updated every week). • Data on one dose, two dose compliance rates.

10. Existing System #3: VAU • Collaboration between CDC/DoD/FDA to assess Anthrax vaccine safety • VSD-like model for military personnel - Defense Medical Surveillance System (DMSS) • Utility - monitoring of pre-pandemic and pandemic vaccine use among early vaccinees (Early indicator – large group) • Pandemic funding has been used to assess ability/feasibility for real time AE monitoring during a pandemic • CDC currently considering how to extend/expand role of this unit beyond its Anthrax vaccine tasking

11. Emerging System #1: AE Active Monitoring • Telemedicine has been used successfully to monitor patients. • TeleWatch is an automated telephone and internet-based system currently in place in the US. • Capabilities: • Collect baseline data • Self-reported AE data (Real Time) • Completeness, accuracy, timeliness • Supports active follow up of select vaccinees

12. Integrated Vaccine Surveillance System (IVSS)AE Active Monitoring • Methods: • 2007 - Participants enrolled at four different clinics upon receiving seasonal flu vaccine. • Daily Diary Entries, even if No symptoms experienced. - Phone or Web. • Made outbound follow-up calls to non-respondents. • Displayed results in real-time on a secured website.

13. AE Active MonitoringParticipating Sites (2 MD, VA, DC)

14. AE Active Monitoring Results • 77% (128/166) of individuals who agreed to participate – reported to the system. • On average participants reported for 3 days post-vaccination. • Five people used > 1 method to report. • Reporting mechanism: • - 48% Phone • - 25% Web - 27% Follow-up Calls

15. AE Active Monitoring - Pilot Study Results

16. AE Active Monitoring - Pilot Study Potential Advantages • Track status of vaccinees. • Reassurance. • Rapid ID of AE (all Vaccinees). • Deployment to and access from multiple locations.

17. Emerging System #2: NEISS/DAWN • Active surveillance systems in place used to monitor injuries and Adverse Drug Events. • Trained chart abstractors review records of every ED visit to report Physician–diagnosed AE. • Pilot 2007: AE from influenza Vaccines. • Timely reporting. • 2 nationally representative networks ED systems. • 8% of US EDs across 48 states and PR. • Baseline data exist (2004-06) for vaccine AE.

18. Supporting Activities #1 Project Area Vaccine Safety Coordinators • POC for CDC planning team. • Coordinate state efforts around AE reporting during pandemic (VAERS & Active SS). • Provides input/feedback to CDC planning team. • 60/62 Project Areas have identified Safety Coordinator.

19. Project Area Vaccine Safety Coordinators Chicago: Lorraine Shoenstadt Molly Sanders Chas DeBolt Tim Horan Karen Donoghue Lynn Bahta Susan Barry Dan Hopfensperger Jacquelyn Roberson Tim Heath Maureen Cassidy Jeff Kingsbury Mary Conant Joanna Briggs Robert Swanson Cynthia Schulte Theresa Thornton Mark Francesconi Karen Rutherford Heather Stafford Mick Bolduc Debbye Rosen Kristin Ryker Bea Burkholder Kay Hunt Doug Banghart Marlee Hawkins NYC: Dr Zimmerman Margaret Huffman Kim Hawkins Daniel Neises Jaynee Browning Barbara Montana Trevor Shoemaker Sandra Sommer Martin Luta Emily Adkins Terry Sapp Darryl Edmisson David Kirschke Amanda Fuller Karen Lewis Andie Denious Marrion Bolar Gayle Kenny William Ledford Shirley Jankelevich Jannifer Anderson LA County Dr El Amin Ronada Anderson Elizabeth Sullivan Ruben Tapia Calandra Bradford Lauren Wood Susan Linciome Marcia Nagao * Rep of Marshall Islands & Rep of Palau

20. S D V Vaccine Safety Monitoring Periods • ++ ++ Vaccine Safety Monitoring Preparation Period Pre-Pandemic Mon - ++ Pandemic Mon Telewatch/IVSS NEISS/DAWN Vax Safety Coordinators

21. Vaccine Safety FrameworkFundamental Components • Acquiring Denominator data • CRA – Vaccine Administration data • DoD – DMSS (VAU) • Active Surveillance Systems • Timeliness of Data • VAERS: web, new mechanism (PHINMS/HL7) • VSD – (RCA) • Active Surveillance Systems (i.e. TeleWatch & IVSS) • Establishing Linkages with other systems • NEISS, CRA, IVSS VAERS • DoD – DMSS (VAU) • FDA, VA, CMS & Industry • Risk Communication • Project Area Coordinators • Vax Safety Emergency preparedness website (Info on Vax Safety, Q&As)

22. Challenges • Complexity of Vax Safety monitoring. • Use of existing safety systems vs development of new. • Rapid vaccine safety assessments. • Utility of VSD and Timeliness of data uncertain at this time. • Numerator/Denominator linkage. • VAUs role in Pandemic vaccine Monitoring. • Utility/Execution of active surveillance systems.

23. Acknowledgements • Office of the Chief Science Officer • Immunization Safety Office (VAERS, VSD, CISA, Brighton, EP) • NCIRD • Immunization Services Division • Division of Bacterial Diseases - VAU • Division of Healthcare Quality Promotion • NEISS/DAWN • Division of Emergency Preparedness and Response • CRA • DoD • Military Vaccine Agency • Project Area Vaccine Safety Coordinators

24. Questions?Nelson Arboleda, MD, MPHImmunization Safety Office (ISO)Office of the Chief Science officer (OCSO/OD)Centers for Disease Control and Prevention (CDC)

25. Indicators of Success • Early recognition and detection of AE through the use of vigilant health surveillance, epidemiological and clinical investigations. • Rapid deployment of active surveillance systems for prompt identification of AE all vaccinees & reassurance. • Assistance to project area vaccine safety coordinators with response and recovery efforts.

26. Indicators of Success Pre-Event • Enhance current systems and activities and develop interventions to ensure continuous Vaccine Safety monitoring. • Decrease the time needed to detect and report serious vaccine AE that cause threats to the public’s health. • Improve the timeliness and accuracy of communications regarding vaccine AE. Event • Decrease the time to identify vaccine adverse events, and implement appropriate interventions for those affected by threats to the public’s health. • Decrease the time needed to provide health guidance to those affected by threats to the public’s health. Post-Event • Decrease the time needed to restore AE reporting to pre-event levels. • Decrease the time needed to implement recommendations to those affected by threats to the public’s health.

27. OPLAN – Readiness Measures • Develop a plan to monitor pre-pandemic/pandemic influenza vaccine adverse events following vaccination. 2. Each Project Area has identified a Vaccine Safety Coordinator for coordinating vaccine adverse event reporting.

28. In the past week, have you experienced soreness at Inj site, fever, pains in your muscles or joints, etc? Sample Phone Prompt from TeleWatch Go to next question Describe where you are having pain On a scale of 1 to 10 (10 being the most), how severe would you rate the muscle and/or joint pain? How many days have you had the pain? Enter the number followed by the # key Has the pain gone away?

29. VAERS Reports by Year

30. AE Active Monitoring - Pilot Study Next Steps • Scale up (diverse settings/populations). • System enhancement. • Interactive Voice Response (IVR) system (transcription). • Multi-lingual system. • Email/text messaging for call back. • Integration w VAERS – Linkage for auto reporting. • Train personnel for sentinel implementation (Project Area & CDC).