Dispositions and Causality Assessment in Pharmacovigilance: Proposing the Dx3 Approach for Assessing Causality with Small Data Sets.

A new approach is proposed for assessing causality in pharmacovigilance. The Dx3 approach is designed to qualitatively evaluate three types of dispositions when assessing whether a particular medicine has or could have caused a certain adverse event. These are: the drug disposition; the pre-disposition of the patient taking the drug (vulnerability) and; the disposition of the patient-drug interaction (mutuality). Each of these three types of dispositions will represent valuable causally relevant evidence for assessing a potential signal of harm. A checklist is provided to guide the assessment of causality for both single individual case safety reports (ICSRs) and case series. Different types of causal information are ranked according to how well suited they are for establishing a disposition. Two case examples are used to demonstrate how the approach can be used in practice for assessment purposes. One aim of the approach is to offer a qualitative way to assess causality and to make the reasoning of different assessors more transparent. A second aim is to encourage the collection of more qualitatively rich patient narratives in the ICSRs. Crucially, we believe this approach can support the inclusion of the single ICSR as a valid and valuable form of evidence.