Bastiaan Sallevelt

40 CHAPTER 2.1 Causality assessment A causality assessment was performed to establish the likelihood of an ADR for all trigger-drug combinations detected with the ADR trigger tool. Data from the admission and discharge letters were taken into account, because both letters could contain relevant information for causality assessment (e.g. to establish a potential time-relationship). A geriatrician (NN) and a clinical pharmacist (BS) independently assessed all trigger-drug combinations. The WHO-UMC system was used for causality assessment, which differentiates between the categories certain, probable, possible, unlikely and unclassifiable [20,21]. Trigger-drug combinations with a causality score of certain, probable and possible were considered ADRs. Before the causality assessment, both appraisers trained with a previously published, Delphi-based chart review method developed to detect drug related admissions by Thevalin et al [22]. The level of agreement between the two appraisers was measured with the Cohen’s kappa test statistic (poor: κ <0.00; slight: κ=0.00–0.20; fair: κ=0.21–0.40; moderate: κ=0.41–0.60; substantial: κ=0.61–0.80; almost perfect: κ=0.81–1.00) [23]. If ratings differed ≥1 WHO-UMC category for causality between the two appraisers, the appraisers discussed each case to reach consensus. The appraisers consulted a third expert (WK, senior geriatrician-clinical pharmacologist) for a final consensus round in case no consensus was reached. ADR recognition by usual care In addition to the causality assessment, EHRs were screened for recognition of ADRs by usual care. Recognition was defined as an explicit documented triggerdrug combination by the attending physician (i.e. a geriatric resident, supervised by a geriatrician) in the admission and/or discharge letter, implying that the triggerdrug combination was identified as an ADR. In addition, explicit documentation of the trigger combined with medication changes in associated drugs (i.e. withdrawal, discontinuation or a dose adjustment) was also considered as being recognised by usual care. Outcomes The performance of the ADR trigger tool was operationalised by calculating the overall PPV for detecting ADRs in general and for each trigger separately. The PPV was defined as the total number of detected trigger-drug combinations divided by the number of ADRs with a causality score of possible, probable or certain. The recognition by usual care was calculated for both ADRs with a causal relationship considered to be possible, probable or certain and for those with a probable or certain causal relationship.