Revised World Health Organization (WHO)’s causality assessment of adverse events following immunization—a critique

Abstract

The World Health Organisation (WHO) has recently revised how adverse events after immunization (AEFI) are classified. Only reactions that have previously been acknowledged in epidemiological studies to be caused by the vaccine are classified as a vaccine-product–related-reaction. Deaths observed during post-marketing surveillance are not considered as ‘consistent with causal association with vaccine’, if there was no statistically significant increase in deaths recorded during the small Phase 3 trials that preceded it. Of course, vaccines noted to have caused a significant increase in deaths in the control-trials stage would probably not be licensed. After licensure, deaths and all new serious adverse reactions are labelled as ‘coincidental deaths/events’ or ‘unclassifiable’, and the association with vaccine is not acknowledged. The resulting paradox is evident. The definition of causal association has also been changed. It is now used only if there is ‘no other factor intervening in the processes’. Therefore, if a child with an underlying congenital heart disease (other factor), develops fever and cardiac decompensation after vaccination, the cardiac failure would not be considered causally related to the vaccine. The Global Advisory Committee on Vaccine Safety has documented many deaths in children with pre-existing heart disease after they were administered the pentavalent vaccine. The WHO now advises precautions when vaccinating such children. This has reduced the risk of death. Using the new definition of causal association, this relationship would not be acknowledged and lives would be put at risk. In view of the above, it is necessary that the AEFI manual be revaluated and revised urgently. AEFI reporting is said to be for vaccine safety. Child safety (safety of children) rather than vaccine safety (safety for vaccines) needs to be the emphasis.

Post-marketing surveillance of adverse events following measles, mumps, rubella and varicella (MMRV) vaccine: retrospecive study in apulia region (ITALY), 2009-2017

“…For serious AEFIs, we retrospectively applied the WHO causality assessment algorithm to classify AEFI as ‘consistent causal association’, ‘inconsistent causal association’, indeterminate’ or ‘not-classifiable’. 8 , 16 For serious AEFIs, 1 month after notification, a follow up was been carried out in order to guarantee a supplemental surveillance of vaccine safety.…”

“…8 According to the WHO algorithm, the association between vaccine and AEFI can be considered not-classifiable when the forms lack of essential data (e.g., the name of the vaccine administered); consistent casual association or inconsistent causal association in presence or absence of a defined causal relationship between adverse event and immunization; indeterminate if there isn’t clear evidence for a causal link, or conflicting trends, or inconsistency with causal association to immunization (this is a potential signal and needs to be considered for further investigation; reviewing factors result in conflicting trends of consistency and inconsistency with causal association to immunization, i.e., it may be vaccine-associated as well as coincidental and it is not possible clearly to favor one or the other). 8 , 15 , 16 …”

Causality assessment of adverse events following immunization: the problem of multifactorial pathology

“…The WHO-UMC scale (https://www.who.int/medicines/areas/quality_safety/safety_efficacy/WHOcausality_assessment.pdf) has been developed in consultation with the National Centres participating in the Programme for International Drug Monitoring and is meant as a practical tool for the assessment of case reports. It offers a simple methodology taking into account the clinical-pharmacological aspects of the case history and the quality of the documentation of the observation (Puliyel and Naik, 2018). Within this arrangement, other criteria such as previous knowledge and statistical chance play a less prominent role in the system, so the surveillance systems are better adapted for the detection of the rare and unexpected events.…”

“…Using this definition of causal association, many adverse events, where the vaccine plays a role as con-cause, remain unrecognized. Others (Puliyel and Naik, 2018) have noted that, according to this scheme, an acute cardiac decompensation after influenza vaccination in an elderly person with chronic cardiac failure might not be considered as causally related to the vaccine. Similarly, sudden death after vaccination of an infant with pre-existing heart disease might not have relationship with the vaccine.…”

Adverse events following measles-mumps-rubella-varicella vaccine: an independent perspective on Italian pharmacovigilance data

“…The debate on the best methods of surveillance in the field of vaccinology should remain open, in the interest of the entire population 1,2,[41][42][43] . Besides the WHO algorithm 15 other criteria developed by various groups working within the greater field of pharmacovigilance are used for causality assessment, such as the World Health Organization Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (WHO-UMC) 44 and the Naranjo algorithm 45,46 .…”