Causality assessment of AEFIs

Most countries have AEFI systems and attach great importance to reports of suspected adverse events. These systems have been successful in identifying severe AEFIs after vaccines are licensed. Follow-up studies are usually needed to further investigate causality of AEFIs.

Although the most reliable way to determine whether an adverse event is causally related to vaccination is through a randomized clinical trial, such trials are limited to the clinical development phase of vaccines. Once a vaccine is licensed, controlled trials are no longer an option owing to ethical reasons (withholding vaccination).

Causality assessment is the systematic review of data about an AEFI case. It determines the likelihood of a causal association between the event and the vaccine(s) received. Causality assessment helps determine:

  • If an AEFI is attributable to the vaccine or the vaccination programme,
  • What steps – if any – need to be taken to address the event. 

The WHO Aide-Memoire on causality assessment serves as a guide to a systematic, standardized causality assessment process for serious adverse events following immunization (including clusters).36

WHO Aide-Memoire: AEFI: Causality Assessment

Causality assessment outcomes help raise awareness of vaccine associated risks among healthcare workers. This, combined with knowledge of benefits of immunization, forms the basis of vaccine information for parents and/or vaccinees.

The quality of a causality assessment depends on the:

  • quality of AEFI case report,
  • effectiveness of AEFI reporting system,
  • quality of the causality review process.

There are five principles that underpin the causality assessment of vaccine adverse events.35

The association of a purported AEFI with the administration of a vaccine should be consistent. The findings should be replicable in different localities, by different investigators not unduly influencing one another, and by different methods of investigation, all leading to the same conclusion(s). The association between the AEFI and the vaccine should be strong in terms of magnitude and also in the dose-response relationship of the vaccine with the adverse event. The association should be distinctive. The adverse event should be linked uniquely or specifically with the vaccine concerned rather than occurring frequently, spontaneously or commonly in association with other external stimuli or conditions. There should be a temporal relationship between the vaccine and the adverse event. For example, that receipt of the vaccine should precede the earliest manifestation of the event. The association should be coherent, that is, plausible and explicable according to known facts in the natural history and biology of the disease.