Reflections on Attribution and Decisions in Pharmacovigilance

Excerpt

In general, a causal relationship depends upon the nature and amount of evidence supporting an attribution hypothesis, such that ‘A causes B’. A can be a sufficient cause of B, meaning that A is always followed by B; or a necessary cause, meaning that B cannot occur without being preceded by A; or both. These deterministic concepts are not relevant to pharmacovigilance. No drug is a sufficient cause of an adverse effect, and there are no examples of necessary causes either. The trigger to modern pharmacovigilance, thalidomide, has come close to being considered a necessary cause of phocomelia, but this is not true. Phocomelia is very rare in the absence of thalidomide but not vanishingly so; x-irradiation is one example of another cause.[1] This example is illuminating also because it shows that the definition of the hypothesis is critical: one must be sure one knows what A and B are. In this case we have used the terms phocomelia, ectromelia, amelia and limb-reduction disorder loosely as synonyms when in reality they are overlapping hierarchical entities. …