title: Comparative analysis of three drug-drug interaction screening systems against probable clinically relevant drug-drug interactions: a prospective cohort study.
abstract: OBJECTIVE
  Drug-drug interaction (DDI) screening systems report potential DDIs. This study aimed to find the prevalence of probable DDI-related adverse drug reactions (ADRs) and compare the clinical usefulness of different DDI screening systems to prevent or warn against these ADRs.
  
  
  METHODS
  A prospective cohort study was conducted in patients urgently admitted to medical departments. Potential DDIs were checked using Complete Drug Interaction®, Lexicomp® Online™, and Drug Interaction Checker®. The study team identified the patients with probable clinically relevant DDI-related ADRs on admission, the causality of which was assessed using the Drug Interaction Probability Scale (DIPS). Sensitivity, specificity, and positive and negative predictive values of screening systems to prevent or warn against probable DDI-related ADRs were evaluated.
  
  
  RESULTS
  Overall, 50 probable clinically relevant DDI-related ADRs were found in 37 out of 795 included patients taking at least two drugs, most common of them were bleeding, hyperkalemia, digitalis toxicity, and hypotension. Complete Drug Interaction showed the best sensitivity (0.76) for actual DDI-related ADRs, followed by Lexicomp Online (0.50), and Drug Interaction Checker (0.40). Complete Drug Interaction and Drug Interaction Checker had positive predictive values of 0.07; Lexicomp Online had 0.04. We found no difference in specificity and negative predictive values among these systems.
  
  
  CONCLUSIONS
  DDI screening systems differ significantly in their ability to detect probable clinically relevant DDI-related ADRs in terms of sensitivity and positive predictive value.
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Neža
authors.initials: N
authors.lastname: Muhič
authors.affiliation: Faculty of Pharmacy, University of Ljubljana, Askerceva cesta 7, 1000, Ljubljana, Slovenia.
authors.forename: Ales
authors.initials: A
authors.lastname: Mrhar
authors.affiliation: Centre for Clinical Toxicology and Pharmacology, Division of Internal Medicine, University Medical Centre Ljubljana, Zaloska cesta 7, 1000, Ljubljana, Slovenia. miran.brvar@kclj.si.|Institute of Pathophysiology, Faculty of Medicine, University of Ljubljana, Zaloska cesta 4, 1000, Ljubljana, Slovenia. miran.brvar@kclj.si.
authors.forename: Miran
authors.initials: M
authors.lastname: Brvar
mesh_terms: D000368:Aged; D004346:Drug Information Services; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data; D006801:Humans; D008297:Male; D011446:Prospective Studies; D062606:Tertiary Care Centers / Q000706:statistics & numerical data
keywords: Actual drug–drug interactions; Adverse drug reactions; Drug–drug interaction screening systems; Potential drug–drug interactions