Who Adverse Events Following Immunization (Aefi) Causality Assessment 815
Who Adverse Events Following Immunization (Aefi) Causality Assessment 815
Who Adverse Events Following Immunization (Aefi) Causality Assessment 815
AIDE MEMOIRE
Purpose: This aide-mmoire serves as a guide to a systematic, standardized causality assessment process for serious adverse events following immunization (including clusters). It is intended to be used by staff at the national (or first sub-national) level.
Standardized case definitions for some AEFIs are available from the Brighton Collaboration at (http://www.brightoncollaboration.org). Use of these definitions is encouraged, especially for serious cases where systematic standardized causality assessment is required.
Severe is not synonymous with serious. A clusteris two or more AEFIs related in time, place and/or by vaccine. Adapted for vaccines from original WHO categories available at http://www.who-umc.org/indes2.html Can be certain in rare instances where there is a demonstrated relationship e.g., VAPP or mumps vaccine-related aseptic meningitis with isolation of the vaccine strain.
Checklist A. Be prepared
Develop a centralized system to verify diagnosis, review, code, collate, store reports and analyse AEFI data. Establish a national (technical) advisory committee. Ensure independence, breadth and depth of technical expertise needed for quality causality review. Provide administrative support to this committee. Adopt standard case definitions for AEFI (Brighton Collaboration definitions if available or national case definitions). Define signal for programme purposes. Define a routine process and adopt criteria for referral of AEFI cases for a systematic causality assessment by the committee. Define frequency of meetings for systematic causality assessment and triggers for exceptional (i.e., urgent) reviews. Develop a process for action on recommendations arising from causality assessment.
Concomitant or preceding conditions Confident diagnosis of lesion Laboratory results favour causation
CAUSALITY
Data quality
Biological plausibility Consistency Reproducibility Reliability
Previous knowledge
Previously Known Reaction
Specificity and strength of association Treatment, risk factors, susceptibility, programme error
C. Conduct systematic standardized causality assessment using the step-by-step guide below
1. Verify reason for reporting: diagnosis; whether serious. . 2. Evaluate and assess factors. 2.1 Is this event known to be related to the vaccine? (Consistency of findings, strength of association.) 2.2 What is the frequency of occurrence of this adverse event? Very common (>1/10); common (>1/100); uncommon (>1/1000); rare (>1/10 000); very rare (<1/10 000), or not previously reported. 2.3 Are similar events known to occur with other diseases? (Specificity of association.) 2.4 Is this event explainable by the biological properties of the vaccine? (Biological plausibility.) 2.5 Is the vaccination-to-event interval compatible with the event? (Temporal relation.) 2.6 Has the patient had similar symptoms in the past? 2.7 Is there a history of concomitant or preceding drug therapy? 2.8 Is there a history of a concomitant or preceding condition? 2.9 Are there other factors that could affect the occurrence of the event? 3. Determine causality category using WHO criteria (see page 1). 3.1 Is this an unknown event in relation to this vaccine? 3.2 Is this a new event? 3.3 Is there lack of sufficient data to reach a more definite conclusion? 3.4 Would the case benefit from a second review if more data became available? 3.5 Based upon answers to the questions above (in this Section), in which WHO category does the case fit best? N.B. not a numerical score. 4. Prepare a brief case summary. 5. Take action on recommendation(s) from the review. 6. Consider the case for education purposes. 7. Communicate findings to immunization programme staff, national regulatory authority, and others (as appropriate).
Words of advice
1. Ensure timely review of cases based on the best case information available: solicit additional information on cases soon after receipt when memory is fresh. 2. Ensure timely triage and referral of serious AEFI for expert systematic causality assessment. 3. Programme expertise is needed for credible quality review, assessment and analysis. 4. Act on recommendations following causality assessment to ensure programme safety and credibility. 5. Feedback and effective communication about the process and the outcomes to stakeholders and the media is vital to avoid misinterpretation.
Assistance for causality assessment is available from the World Health Organization through the Department of Immunization, Vaccines & Biologicals. Additional information on AEFI surveillance, investigation, management and causality assessment, and on vaccine safety communication can be found on the Web at http://www.who.int/immunization_safety/en/ Department of Immunization, Vaccines and Biologicals World Health Organization 20 Avenue Appia, CH-1211 Geneva 27, Switzerland Fax: +41 22 791 4210