Contextualized Drug–Drug Interaction Management Improves Clinical Utility Compared With Basic Drug–Drug Interaction Management in Hospitalized Patients

Abstract

Drug-drug interactions (DDIs) frequently trigger adverse drug events or reduced efficacy. Most DDI alerts, however, are overridden because of irrelevance for the specific patient. Basic DDI clinical decision support (CDS) systems offer limited possibilities for decreasing the number of irrelevant DDI alerts without missing relevant ones. Computerized decision tree rules were designed to context-dependently suppress irrelevant DDI alerts. A crossover study was performed to compare the clinical utility of contextualized and basic DDI management in hospitalized patients. First, a basic DDI-CDS system was used in clinical practice while contextualized DDI alerts were collected in the background. Next, this process was reversed. All medication orders (MOs) from hospitalized patients with at least one DDI alert were included. The following outcome measures were used to assess clinical utility: positive predictive value (PPV), negative predictive value (NPV), number of pharmacy interventions (PIs)/1,000 MOs, and the median time spent on DDI management/1,000 MOs. During the basic DDI management phase 1,919 MOs/day were included, triggering 220 DDI alerts/1,000 MOs; showing 57 basic DDI alerts/1,000 MOs to pharmacy staff; PPV was 2.8% with 1.6 PIs/1,000 MOs costing 37.2 minutes/1,000 MOs. No DDIs were missed by the contextualized CDS system (NPV 100%). During the contextualized DDI management phase 1,853 MOs/day were included, triggering 244 basic DDI alerts/1,000 MOs, showing 9.6 contextualized DDIs/1,000 MOs to pharmacy staff; PPV was 41.4% (P < 0.01), with 4.0 PIs/1,000 MOs (P < 0.01) and 13.7 minutes/1,000 MOs. The clinical utility of contextualized DDI management exceeds that of basic DDI management.

Adverse drug events caused by three high‐risk drug–drug interactions in patients admitted to intensive care units: A multicentre retrospective observational study

“…28 However, since both drug (groups) have nephrotoxic potential and use of diuretics has been identified as a risk-factor for aminoglycosideinduced nephrotoxicity, caution is advisable when they are administered at the same time. [45][46][47] The PPV findings for our DDI-AKI and DDI-INR + e-triggers are encouraging. Use of e-triggers can largely automate the process of ADE detection, and save substantial time for patient chart review by clinical experts.…”

“…This urges further improvement of the logic-based rules behind pDDI alerts to make them fit better to a specific clinical context and/or patient factors. 6,46,47 Given the high variety of pDDIs in the ICU, This study also underlines the multifactorial nature of adverse (drug) events in ICU patients. 48 This multifactorial nature explains why only a small proportion of DDI-ADEs in our study (6%) was assessed as having a nearly certain causality.…”

“…At the same time, the detected DDI‐ADEs occurred despite CDSS being in place in the majority of our participating ICUs. This urges further improvement of the logic‐based rules behind pDDI alerts to make them fit better to a specific clinical context and/or patient factors 6,46,47 . Given the high variety of pDDIs in the ICU, 1,8 more research is needed to investigate ADE potential of a broader sample of pDDIs, as a way to optimize CDSS effectiveness.…”

“…In the G‐Standaard, this combination is earmarked as having insufficient evidence‐base and therefore no alerting is indicated 28 . However, since both drug (groups) have nephrotoxic potential and use of diuretics has been identified as a risk‐factor for aminoglycoside‐induced nephrotoxicity, caution is advisable when they are administered at the same time 45–47 …”

Potentially clinically significant drug-drug interactions in older patients admitted to the hospital: A cross-sectional study

“…For example, metamizole (dipyrone) generates theoretical DDIs that affect blood pressure and kidney functions due to being listed among other NSAIDs. Recently Wasylewicz et al have shown that contextualized DDI management can considerably decrease the number of irrelevant DDI alerts and thereby increase the time available to interpret relevant DDI alerts ( Wasylewicz et al, 2022 ). Although it may be difficult to operationalize certain factors to reduce unnecessary alerts, these factors can provide useful information for clinicians to decide whether to override an alert ( Reese et al, 2022 ).…”