1. DEPARTMENT OF HEALTH AND HUMAN SERVICES Monitoring Anthrax Vaccine Adverse Events Defense Medical Surveillance System (DMSS) Michael McNeil, MD, MPH National Immunization Program NVAC, June 4 th, 2003

2. DEPARTMENT OF HEALTH AND HUMAN SERVICES Overview of the DMSS Project  How were the topics selected?  Potential Topics  Criteria for Prioritizing Topics  Timeline  Next Steps

3. DEPARTMENT OF HEALTH AND HUMAN SERVICES Sources for Topic Selection:  Institute of Medicine (IOM)  Anthrax Vaccine Expert Committee (AVEC)  Vaccine Adverse Event Reporting System (VAERS)  Medical and Public Health Literature  CDC, FDA, DoD  Public Opinion

4. DEPARTMENT OF HEALTH AND HUMAN SERVICES Possible Topics for Investigation Endocrine SystemIntegument System Diabetes mellitus Rash with mucosal involvement Nervous SystemMusculoskeletal System Peripheral neuropathyJoint disorders Guillain-Barre SyndromeMyositis Demyelinating conditions

5. DEPARTMENT OF HEALTH AND HUMAN SERVICES Possible Topics for Investigation Cardiovascular System Atrial fibrillation Vasculitis Psychiatric Disorders Mood disorder Other Topics Syndromic illness Loss of duty Death Medical encounters Unintentional injury

6. DEPARTMENT OF HEALTH AND HUMAN SERVICES Potential Criteria for Prioritizing Topics  Frequency of Occurrence  Feasibility  Severity of Effect  Likelihood of Association  Programmatic Interventions  Public Health Concern

7. DEPARTMENT OF HEALTH AND HUMAN SERVICES Frequency of Occurrence  Reports from VAERS  Reports from DMSS  Reports from other sources

8. DEPARTMENT OF HEALTH AND HUMAN SERVICES Feasibility  Well-characterized natural history  Established pathophysiology  Practical issues (e.g., obtaining medical charts)  Basis for making the diagnosis  Subjective (e.g., symptoms)  Objective findings (e.g., laboratory tests)

9. DEPARTMENT OF HEALTH AND HUMAN SERVICES Feasibility (cont’d)  Universally accepted case-definition  Specificity  Sensitivity  Positive predictive value  Existence of a specific ICD-9 code  Identifiable/available study and comparison groups of adequate size  Ethical concerns

10. DEPARTMENT OF HEALTH AND HUMAN SERVICES Severity of Effect  Acute vs. chronic course  Impact on functional status and/or quality of life  Life-threatening  Hospitalization

11. DEPARTMENT OF HEALTH AND HUMAN SERVICES Likelihood of Association or Causation  Published studies – strength of findings  Consistency of findings  Biological plausibility  Temporal association of effect with putative cause  Demonstration of dose-response effect

12. DEPARTMENT OF HEALTH AND HUMAN SERVICES Programmatic Interventions  Permits screening and possible deferral of AVA recipients  Availability of treatment(s)  Altered use of AVA  Reformulation of vaccine  Change in site, dosage, route of administration, and pre- treatment/site care

13. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Concern  Sources of Concern:  AVEC  VHC  CDC  Advocacy groups  News media  Level of Concern  Congress  Data Safety Monitoring Board (DSMB)  IOM  DoD  FDA

14. DEPARTMENT OF HEALTH AND HUMAN SERVICES Timeline  MOU  Office space  Equipment  Oct. 15 th IOM January 2003 July 2002

15. DEPARTMENT OF HEALTH AND HUMAN SERVICES Timeline  MOU  Office space  Equipment  Oct. 15 th IOM  Jan. 30th Meeting  Recruitment  Tasks created  Topics selected  Criteria  Committees March 2003 January 2003 July 2002

16. DEPARTMENT OF HEALTH AND HUMAN SERVICES Timeline  MOU  Office space  Equipment  Oct. 15 th IOM  Jan. 30th Meeting  Recruitment  Tasks created  Topics selected  Criteria  Committees April 2003 January 2003 July 2002 March 2004  Criteria papers (April-May)  Hire Staff (May-June)  Prioritize topics (July)  Protocol (July-Mar)

17. DEPARTMENT OF HEALTH AND HUMAN SERVICES Timeline for the External Consultative Committee  NVAC Meeting  Select members  Topic papers  Prioritize topics (July – August 2003) August 2003 July 2003 June 2003 March 2004  Protocol Review (March 2004)

18. DEPARTMENT OF HEALTH AND HUMAN SERVICES Acknowledgements DOD Mark Rubertone John Grabenstein John Brundage Jeff Lange DMSS Staff CDC Ben Schwartz Bruce Tierney Phil Rhodes Stacey Martin Paul Stehr-Green Betsy Cadwell Roseanne English- Bullard Kelly Bell FDA Bob Ball Dale Burwen Jane Woo FOH Wayne Grant Richard Horn AVEC