The SIMPLIFY Study (2016-2021) is conducted together with 14 Dutch Intensive Care Units (ICUs), the National Intensive Care Evaluation Foundation, IteMedical, Z-Index, KNMP Geneesmiddelen Informatie Centrum, and IC Connect. For the purpose of this study a database was created containing real-world data on medication administrations of > 150.000 ICU admissions.

In the Intensive Care environment, where potentially interacting drugs are frequently co-prescribed, there is no consensus on the clinical relevance of these potential drug-drug interactions (pDDIs). In addition, we lack evidence on the effectiveness of computerised decision support systems (CDSS) on reducing pDDIs. 

To improve medication safety in Dutch ICUs by establishing pDDI frequency and clinical relevance in the ICU. To subsequently assess in a stepped-wedge trial the impact of customising CDSS according to clinical relevance on reduction of pDDIs (main outcome). Furthermore, to investigate clinical manifestations of pDDIs and develop patient friendly information about ICU medication and pDDIs.

Our systematic review of 26 studies on pDDIs in the ICU setting showed that reporting on pDDIs needs to be improved. Of the 148 pDDI types for which ICU physicians get CDSS alerts when prescribing medication to ICU patients, 38% was assessed as not clinically relevant in the ICU in our Delphi study. The mean number of pDDIs per 1000 medication administrations was 70.1. However, this average dropped significantly to 31.0 using our list of clinically relevant pDDIs. Our cluster randomized stepped-wedge trial showed that tailoring CDSS alerts for pDDIs to the ICU environment, leads to 12% decrease in the number of administered high-risk drug combinations (95% CI 5–18%; p=0·0008). Additionally, patient monitoring for potential consequences of DDIs improved by 9% (95% CI 6–11%; p<0·0001), and the length of stay in the ICU was reduced by 6% (95% CI 2–10%; p=0·0021).