Improving the specificity of drug-drug interaction alerts: Can it be done?

Am J Health Syst Pharm. 2022 Jun 23;79(13):1086-1095. doi: 10.1093/ajhp/zxac045.


Purpose: Inaccurate and nonspecific medication alerts contribute to high override rates, alert fatigue, and ultimately patient harm. Drug-drug interaction (DDI) alerts often fail to account for factors that could reduce risk; further, drugs that trigger alerts are often inconsistently grouped into value sets. Toward improving the specificity of DDI alerts, the objectives of this study were to (1) highlight the inconsistency of drug value sets for triggering DDI alerts and (2) demonstrate a method of classifying factors that can be used to modify the risk of harm from a DDI.

Methods: This was a proof-of-concept study focused on 15 well-known DDIs. Using 3 drug interaction references, we extracted 2 drug value sets and any available order- and patient-related factors for each DDI. Fleiss' kappa was used to measure the consistency of value sets among references. Risk-modifying factors were classified as order parameters (eg, route and dose) or patient characteristics (eg, comorbidities and laboratory results).

Results: Seventeen value sets (56%) had nonsignificant agreement. Agreement among the remaining 13 value sets was on average moderate. Thirty-three factors that could reduce risk in 14 of 15 DDIs (93%) were identified. Most risk-modifying factors (67%) were classified as order parameters.

Conclusion: This study demonstrates the importance of increasing the consistency of drug value sets that trigger DDI alerts and how alert specificity and usefulness can be improved with risk-modifying factors obtained from drug references. It may be difficult to operationalize certain factors to reduce unnecessary alerts; however, factors can be used to support decisions by providing contextual information.

Keywords: alerts; clinical decision support; drug-drug interactions; interoperability.

MeSH terms

  • Data Collection
  • Decision Support Systems, Clinical*
  • Drug Interactions
  • Humans
  • Medical Order Entry Systems*
  • Risk Factors