Comparability of Vaccine Safety Data Development of Standardized Case Definitions for Adverse Events Following Immunization Katrin S. Kohl, MD, MPH Dr. med. Jan Bonhoeffer

15 Countries with >2 Members (N=227) 3

17 Countries with < 2 Members (N=21) Brazil Denmark Finland Hong Kong India Israel Jordan Malaysia Mexico New Zealand Pakistan Singapore S.Korea South Africa Thailand The Gambia The Philippines

Process 1) Inventory of existing case definitions 2) Development of draft case definition document through working group consensus 3) Review and evaluation of draft case definition through reference group and field testing 4) Finalization and global dissemination of definition

Evaluation Process Surveys to assess applicability and clarity of drafts 2 – 3 months comment period 3 months for final changes by working groups Reference group members: Representatives of organizations (e.g., AAP, AAFP, PIDS, WHO, FDA, EVM) Individuals with expertise in respective area Field testing, whenever possible

Time Line Definition Development Mar Begin of work of first 6 WG Jun Launch of website 2002 Feb Draft definition documents Apr Start of next 7 WG May Reconvene WG for first 6 AEFI Jul Final draft for first 6 AEFI

First six AEFI definitions 1)Fever 2)Local reactions 3)Intussusception 4)Inconsolable crying 5)Seizure 6)Hypotonic-hyporesponsive episode

AEFI Definition Document - Format - Preamble: Rationale, methodology Definition: 3 levels of evidence Guidelines: Case determination, reporting, data presentation

Fever Level 1 of evidence (Definite) Fever is defined as a temperature elevation of >38 degree Celsius Level 2 of evidence (Probable) Not applicable Level 3 of evidence (Possible) Not applicable “Fever suspected, with insufficient evidence”

Injection Site Nodule Level 1 of evidence (Definite) The presence of Discrete or well demarcated soft tissue mass Firm AND at injection site In the absence of Abscess formationAnd/OR Warmth And/OR Erythema Level 2 of evidence (Probable) Not applicable Level 3 of evidence (Possible) Not applicable

Intussusception Level 1 of Evidence (Definite) Surgical criteria AND/OR Radiological criteria AND/OR Autopsy criteria Level 2 of Evidence (Probable) Clinical criteria (2 major OR 1 major & 3 minor criteria) Level 3 of Evidence (Possible) Clinical criteria (4 or more minor criteria)

Inconsolable Crying Level 1 of evidence (Definite) The presence of Loud vocal sound expressing sorrow or fear, which is persistent, i.e. continuous AND unaltered for > 3 hours In the absence of Response to any attempt to console the crying (e.g. by means of feeding, comforting, analgesics) Level 2 of evidence (Probable) Not applicable Level 3 of evidence (Possible) Not applicable

Episode of neuronal hyperactivity resulting in a sudden involuntary Major motor eventAND/OR Sensory disturbanceAND/OR Autonomic dysfunctionAND/OR Behavioral abnormalities AND/OR Impairment of consciousness Classification by International Classification of Seizures. Seizure

Generalized Convulsive Seizure Level 1 of Evidence (Definite) Neurophysiological criteria AND/OR Clinical criteria: Witnessed sudden loss of consciousness AND generalized, tonic, clonic, tonic-clonic or atonic motor manifestations

Generalized Convulsive Seizure Level 2 of Evidence (Probable) UnconsciousnessAND generalized tonic, clonic or tonic-clonic or atonic motor manifestations Level 3 of Evidence (Possible) Unconsciousness AND Other generalized motor manifestations

HHE Level 1 of evidence (Definite) The sudden onset of Limpness or muscular hypotonia AND Reduced responsiveness or unresponsiveness AND Pallor or cyanosis throughout the episode In the absence of a more specific diagnosis for above signs …

HHE Level 2 of evidence (Partial) The sudden onset of  Two of the three definite inclusion criteria AND  The third one noticed to be absent Level 3 of evidence (Possible) The sudden onset of  Two of the three definite inclusion criteria

1)Allergic Reaction 2)Rash 3)Asthenia 4)Paresthesia 5)Sudden Infant Death Syndrome 6)Myalgia 7)Idiopathic Thrombocytopenia Selection of next 7 AEFI Volunteers are welcome!

Your Help! Building up reference group Field testing of definitions Volunteers next working groups Working group coordinator Dissemination and implementation strategy Methodological issues Web-based chat room Formal method group