# Presentation: 902052

## 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**

## 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**

## 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**

## 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**

## 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

- 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**

## www.brightoncollaboration.org  

- _[www.brightoncollaboration.org](http://www.brightoncollaboration.org/)_**  **
** ****secretariat@brightoncollaboration.org**

## Network  of Participants (N=1819) June 2008

**Network  of Participants ****(N=1819) ****June 2008**

**24 countries**

**with **_**>**_** 2 participants**

**with 1 participant**

**69 countries**

## 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

## Highlighted Achievements

**“****Success is the progressive realization of a predetermined worthwhile goal”**** ****Paul J Meyer**

## 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***

## 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]***

## 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

## 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

**Notes:**
What are the foreseeable benefits and what is achieved with the money spent? 

In surveillance systems, the definitions and guidelines provide a useful  tool for the development of check lists for active follow-up and validation of data - report or signal generated. 

This standardized safety assessment leads to comparability with other studies and hence improves the value of surveillance data. 

## 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)

## 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

**.**
**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**

## 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).

## 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_download.html**

**	****	****	****Many Thanks!**