1. The Brighton Collaboration: An Overview and Preparedness for Pandemic Influenza Jane Gidudu MD, MPH Team leader April Compingbutra MPH, Paige Lewis MPH The Brighton Collaboration Team, Immunization Safety Office, Office of the Chief Science Officer CDC-Atlanta

2. Mission The Brighton Collaboration is an international voluntary collaboration with a mission to facilitate the development, evaluation, and dissemination of high- quality information about the safety of human vaccines

3. Global Standardization Vacines are used worldwide Standardization of Adverse Events Following Immunization (AEFI) Facilitates comparability and communication of safety data Enhancement of trust in current immunization programs

4. Background – The Need Safety cannot be measured directly, only inferred from the relative absence of AEFIs Assessing safety requires standardized terminology of AEFI Lack of a standard “vocabulary” (i.e., case definitions & guidelines) for AEFI has hindered comparability of vaccine safety data

5. A global collaboration to address this “missed opportunity” Development of standardized case definitions and guidelines Case definitions categorized by levels of evidence  Clinical trials vs. post marketing surveillance  Developed vs. developing countries Background – The Solution

6. www.brightoncollaboration.org secretariat@brightoncollaboration.org

7. Network of Participants (N=1819) June 2008 24 countries with > 2 participants with 1 participant 69 countries

8. Brighton Process Select or prioritize an adverse event to be defined Initiate a 6-step process  Review literature for available evidence  Form working groups  Develop draft definitions and guidelines  Review and evaluate draft  Review and receive endorsement from the CIOMS and WHO vaccine pharmaco-vigilance committee  Finalize and disseminate documents

9. Highlighted Achievements “Success is the progressive realization of a predetermined worthwhile goal” Paul J Meyer

10. Case Definitions Anaphylaxis Aseptic meningitis Encephalitis, myelitis, and ADEM Fever Fatigue Hypotonic-hyporesponsive episode Intussusception Local reactions  abscess  cellulitis  nodule  induration  swelling Persistent crying Rash Seizure Thrombocytopenia Unexplained sudden infant death including SIDS Vaccinia  eczema vaccinatum  inadvertent inoculation  generalized vaccinia  progressive vaccinia  robust take

11. Case Definition Format (5 Categories ) Level 1 of diagnostic certainty [most specific least sensitive] Level 2 of diagnostic certainty [intermediate] Level 3 of diagnostic certainty [least specific, most sensitive] 2 Additional categories for data analysis  Reported [AEFI] with insufficient evidence  Not a case of [AEFI]

12. Example: Intussusception Level 1  Surgical criteria AND/OR  Radiological criteria AND/OR  Autopsy criteria Level 2  Clinical criteria  2 Major* OR I major & 3 minor ¥ criteria Level 3  Clinical criteria  >4 minor ¥ criteria * Major criteria include: evidence of intestinal obstruction, features if intestinal invagination, evidence of intestinal vascular compromise or venous congestion ¥ Minor criteria include: predisposing factors such as abdominal pain, vomiting lethargy, pallor, hypovolemic shock, plain abdominal radiograph

13. Applicability in Surveillance Systems Check list for active follow-up Validation of data  Report & signal generation Standardized safety assessment  Comparability with other studies Improved value of surveillance data

14. Global Recognition and Recommendation World Health Organization (WHO) US Centers for Disease Control and Prevention (CDC) European Centers for Disease Control and Prevention (ECDC) US Food and Drug Administration (FDA) Council for International Organization of Medical Sciences (CIOMS) European Agency for the Evaluation of Medicinal Product (EMEA) American Academy of Pediatrics (AAP) Council for International Medical Sciences (CIOMS)

15. Evaluating Brighton case definitions in the VAERS system beginning with adverse events [anaphylaxis, bells palsy] anticipated to occur in mass influenza vaccination setting. Validating these case definitions for incorporation into case assessment report form for monitoring adverse events following immunization. We strive to establish a system that can flag confirmed cases of adverse events in our VAERS system for evidence based decisions Pandemic Activities

16. Summary The Brighton Collaboration is a growing global network of experts and scientists concerned with vaccine safety. The common goal is to facilitate data comparability across studies in different settings. We have a voluntary platform for over 1800 participants in over 90 countries. The collaboration consists of various disciplines (academia, patient care, industry, regulatory and public health organizations).

17. Summary (continued) A total of 22 case definitions have been published in Vaccine. We use a systematic and transparent, scientific process. Our team is currently focusing on key pandemic preparedness activities such as evaluating adverse events anticipated in pandemic influenza We strive to establish a system that can flag confirmed cases meeting our validated criteria Case definitions can be accessed freely online at: http://www.brightoncollaboration.org/internet/en/index/definition___guidelines/document_do wnload.html

18. Many Thanks!