Causality assessment of Adverse Events following Immunization
Attribution of causality to AEFI, especially those considered severe, of public importance, and programmatically disruptive, are critical for ensuring vaccine safety. In 2005, WHO published an aide-mémoire to a systematic, standardized causality assessment process for serious AEFI (including clusters), providing a method for individual causality assessment to be used by staff of national immunization programmes, regulatory authorities and pharmacovigilance or surveillance departments.1 After 7 years, several limitations had been identified during its use in the field, including: the need for more detailed guidance on the elements required to perform the assessment of causality, confusion over the terms used to classify the likelihood of association of the event to the vaccine, and the incomplete use of parameters for establishing causal association.
Following the GACVS decision to review the causality assessment system in December 2010, a working group was established to review the aide-mémoire and develop a method that would be simple, objective, adaptable and evidence-based when used by countries with different resources and capabilities. After concluding a thorough review of the most innovative methods available for determining causation for drugs and biologicals, an algorithmic scheme that incorporates additional elements of causation was designed. The guide was harmonized after the Clinical Immunization Safety Assessment (CISA) network’s newly developed algorithm which is available in the USA2 and the new definition of AEFI proposed by the Council for International Organizations of Medical Sciences (CIOMS).3
The new WHO proposed method allows the National Committees for AEFI case review and causality assessment to screen serious cases reported by their surveillance system for completeness and quality of information, ensuring the objectiveness of the assessment. Cases deemed incomplete are directed towards additional case investigation and review. A checklist containing the elements of causality assessment was included to guide the committee or the assessor to gather the evidence needed for case review, and when completed allows the application of an algorithm that helps determine if the AEFI could be consistent or inconsistent with an association with the immunization, or is deemed indeterminate due to lack of evidence. A repository of all AEFI cases sorted through this new document is considered critical and recommended to allow for future signal detection and determining the need for additional epidemiological studies.
GACVS recognizes the boundaries of the newly developed method, mainly the limitations in the ability to associate novel, previously unknown AEFIs potentially associated with immunizations, and restrictions due to insufficient information available for individual cases. However, the new AEFI causality assessment system will provide a standardized and transparent method that allows stakeholders to understand the nature of the decision-making process, and pave the way for future evaluation of the guide to refine its effectiveness. GACVS has recommended that this new WHO AEFI causality assessment approach should be made public as soon as it is finalized, and that complementary materials and simple software be developed for use in countries to enable immunization staff to field-test the algorithm. Of the next steps deemed most important is the development of a booklet to codify the algorithm and train countries in its use. The committee encouraged the subgroup to further develop the product and endorsed the work process.
- Aide-mémoire: Adverse events following immunization (AEFI): causality assessment. Geneva, World Health Organization, 2005. Available from http://whqlibdoc.who.int/aide-memoire/a87773_eng.pdf; accessed July 2012.
- Halsey NA et al. Algorithm to assess causality after individual adverse events following immunizations. Vaccine, 2012. Available online at http://www.ncbi.nlm.nih.gov/pubmed/22507656, accessed July 2012.
- Definitions and application of terms for vaccine pharmacovigilance. Geneva, World Health Organization/ Council for International Organizations of Medical Sciences, 2012. Available at http://whqlibdoc.who.int/publications/2012/9789290360834_eng.pdf, accessed July 2012.