Veterinary pharmacovigilance. Part 5. Causality and expectedness

Abstract

In the European Union and elsewhere there is a requirement to ascribe causality to adverse drug reactions which occur in treated animals. In the EU, the ABON system of causality assessment is used but the assignment of causality assigned is not always self evident, and it may be complicated for a variety of reasons. In this paper, the approaches to causality assessment, based on a number of key criteria which examine the administration of the drug in relation to the sequence of ensuing events and the presence of biological plausibility are examined, along with the utility of using algorithms to facilitate this process. Unexpected adverse drug reactions usually require expedited reporting, depending on national or regional regulatory requirements. Again, deciding on what might constitute an expected (or unexpected) adverse reaction, particularly when a product may be intended for use in a number of species, and when within any one species a number of breeds may be treated, is not necessarily a straightforward issue. However, an approach to facilitate the decision- making process, based on a similar approach used in the pharmacovigilance of human medicinal products is discussed.

Seizure occurrence in dogs under primary veterinary care in the UK: prevalence and risk factors

“…This effect appears to be quite sex‐specific however and no significant effect of neutering on seizure risk in males was noted. However, a word of caution in relation to the potential benefits of neutering in bitches: studies such as the current cross‐sectional analysis can only show statistical association and must not be taken on their own as evidence of causality . It is also possible that these associations stem from reverse causality effects whereby bitches that show seizures might be more likely to be removed from the breeding pool and then neutered rather than the other way around .…”

Potential cutaneous hypersensitivity reaction to an inactive ingredient of thyroid hormone supplements in a dog

“…Various algorithms have been developed to help establish a diagnosis of adverse drug reactions . Indeed, this can be challenging when the patient is treated with multiple medications at the same time as the reaction and/or the clinical signs also correspond to other aetiologies.…”

“…Indeed, this can be challenging when the patient is treated with multiple medications at the same time as the reaction and/or the clinical signs also correspond to other aetiologies. Based on the clinical signs, timing, outcomes of de‐challenges and re‐challenges, this event would obtain a high score in all adverse drug reaction algorithms (ABON, RUCAM, Naranjo), making it a “very likely” drug allergic reaction. Furthermore, no lesions have been observed after treatment for 1.5 years with a thyroid supplement lacking the suspect inactive ingredients in the two previous medications associated with the clinical reactions.…”

Veterinary pharmacovigilance. Part 1. The legal basis in the European Union

“…One of the important issues addressed in Volume 9 is the question of causality. This is done using the ABON system (Woodward & Gray, 1994): The issues surrounding causality are dealt with in a separate paper in this series and so are not dealt with further here (Woodward, 2005). However, it should be noted that it may be difficult to assess causality from a single case report, or indeed from a small number of case reports and in those cases, it may be more practical to make assessments of causality by the analysis and evaluation of a series of reports, where trends can be identified and generalities and comparisons made (Meyboom et al, 1997;Jones, 2000;Keck & Ibrahim, 2001).…”