Re: Modernising vaccine surveillance systems to improve detection of rare or poorly defined adverse events
The comment from Dr Puliyel is acknowledged. His criticism of my use of the examples of intussusception and narcolepsy of the robustness of the “current system” is a fair one without a more detailed description of the differences in AEFI reporting, causality assessment, and signal detection within the global context.
The WHO AEFI causality assessment was developed by the Vaccines Safety Group at the WHO with the support of the Global Advisory Committee on Vaccine Safety. The target user group for this classification system are persons working in countries in whom vaccines are administered via WHO sponsored public health programmes. Those persons are largely concerned with the detection of "signals" of changes in frequency of the more common, expected events which could suggest vaccine quality-related problems, immunisation errors, or multi-use vial contamination, etc. At the current time, most AEFI reports collected and assessed with the WHO AEFI Causality Classification remain within the databases of the public health programmes and are not forwarded into the databases of the national pharmacovigilance centres of most lower and middle income countries.
In contrast, more general guidance for causality assessment, such as the WHO-UMC causality criteria and the Naranjo algorithm, were developed by various groups working within the greater field of pharmacovigilance. The target user groups for these classification systems are those persons working within national pharmacovigilance centres, usually working within or collaboratively with national regulatory centres,and responsible for post-marketing safety surveillance of both drugs and vaccines used within their countries. Within such centres adverse event reports for drugs and vaccines are often maintained within a single database (one notable exception being the USA), and causality assessment is approached in a similar way for all products. Detection of "signals" within the database can be conducted qualitatively (on a "case-by-case" basis) and/or quantitatively (via statistical screening ). Higher income countries which do not rely upon implementation of vaccine administration through WHO public health programmes will handle reports of AEFI through these national pharmacovigilance centres.
Furthermore, it is worth noting that most reports of AEFI contained with Vigibase, the database of individual case safety reports for the WHO Programme of International Drug Monitoring, are from countries who channel reports of AEFI through their national pharmacovigilance system, and therefore most reports within the global database have not been subject to WHO AEFI causality assessment.
Taking the specific example of narcolepsy, reports of this condition in association with Pandemrix, an H1N1 pandemic vaccine, were initially received into the national pharmacovigilance centres of Sweden and Finland, and therefore they were not subject to causality assessment by the WHO AEFI classification system. This signal was detected, in fact, because these clusters of reports in young children were "unexpected" , by both the reporting physicians (based upon their clinical practice) and by the regulators (based upon the expected reporting patterns within their national databases of suspected adverse drug reactions).
The current system referred to as "robust" within this analysis therefore refers to practice of vaccine pharmacovigilance by national pharmacovigilance/regulatory centres, not that of national immunisation centres routinely utilising the WHO-AEFI causality classification system.
Competing interests: No competing interests