Provider and pharmacist responses to warfarin drug–drug interaction alerts: a study of healthcare downstream of CPOE alerts

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This article studies the downstream effects of Computerized Physician Order Entry alerts and how critical it really gets. [1]


Department of Veterans Affairs (VA) medical centers have had a CPOE system implemented for more than 10 years in 150 hospital environments. At the San Francisco VA Medical Center (SFVAMC), CPOE with basic decision support is utilized throughout the institution, bar code recognition technology is in place for verification and documentation of inpatient medication administration, and the patient medical record is fully integrated and available online. Providers are prompted when an ordered medication interacts with medications already included on the patient's active inpatient and outpatient medication profile. At the time of this study, these interaction alerts provide only information about interaction severity. When the interaction is categorized as a potentially critical drug–drug interaction (cDDI), providers are required to either cancel the order or enter an explanation as free text before over-riding the alert. Providers have a single text box to enter the reason for over-ride for all order checks being over-ridden at that time. When a pharmacist subsequently processes the order with a cDDI alert, they view the provider's over-ride response and are prompted to document their own intervention before processing the order; however, pharmacists are able to bypass this last step. Studies focused on CPOE alerts and warfarin management to date have shown mixed results on provider actions. A study of alerts in the long term care setting found that 12% of the DDI alerts seen by providers were for warfarin interactions and that providers were only slightly more likely to take appropriate action if they were alerted versus a non-alerted control. The objective of this study was to investigate the utility of cDDI alert processes by categorizing provider and pharmacist responses to warfarin cDDI alerts as clinically appropriate, tracking providers' actions after cDDI alerts, and determining the occurrence of warfarin ADE following the alerts.


The VA Veterans Health Information Systems and Technology Architecture (VistA) database was queried for patients who had at least one cDDI alert to warfarin over-ridden during an acute care hospital stay. Admissions were included if the patient received warfarin and the interacting medication during their admission, were admitted from January 1, 2007 to June 30, 2008, and had an admission lasting at least 72 h. Admissions were excluded if the patient was on both warfarin and the interacting medication before admission or no INR was calculated during admission before warfarin was started. The alert of interest (AOI) was the first cDDI alert with warfarin that met all inclusion criteria. Provider and pharmacist responses when over-riding the cDDI alerts were categorized as clinically appropriate (hereafter referred to as appropriate), inappropriate, or absent based on criteria published by Grizzle [2]


During the study period, there were 555 acute care admissions with a cDDI alert to warfarin over-ridden during the hospital stay. After chart review, 137 admissions were included in this study, accounted for by 133 unique patients. A total of 418 admissions were excluded, some due to multiple reasons. Grounds for exclusion included being on both medications prior to admission (294), failure to receive both medications together during the admission (171), admission lasting less than 72 h (109), or other miscellaneous reasons. The most common categories for responses are listed. For providers, the most common responses were ‘OK’ or ‘MD aware’ which were categorized as ‘Provider aware but no additional reason.’ Due to the set up of the system, providers were not allowed to have an absent response. For pharmacists, no response was most common, categorized as absent. The only variable found to be associated with inappropriate provider response was an increased number of non-critical alerts at the time of the AOI (p=0.01). Alerts with an inappropriate response had an average of four simultaneous non-critical alerts versus 2.4 simultaneous non-critical alerts for over-rides with appropriate responses. On multivariate analysis as well, the only factor associated with an inappropriate response was the number of simultaneous non-critical alerts. Providers were no more likely to have an appropriate response to amiodarone than to vitamin E, the two most common medications involved in the cDDI. Analysis was not completed on factors associated with a inappropriate or absent pharmacist response due to the small number of text responses. In 42% of admissions, providers decreased, held, or stopped warfarin within 72 h of the AOI. Providers adjusted or stopped the interacting medication in 11% of admissions. There were 50 ADE related to warfarin documented in this study, representing 36.6% of admissions.


The large number of CPOE alerts that providers and pharmacists must respond to in the VA CPOE system is associated with inappropriate responses to cDDI alerts, even with high risk medications such as warfarin. This decision support tool is not being fully utilized by providers at the point of care and review by pharmacists does not improve documentation of over-ride rationale. While most of the patients in this study had appropriate follow-up, the high rate of ADE suggests a need to improve the quality of appropriate medication management following cDDI alerts. Although the rationale for DDI alerts is reasonable, improvements in design are needed to overcome the prevalence of inappropriate responses to alert over-rides. This study provides additional support for the necessity of improving alert utility in existing and future CPOE systems.


We must be very careful about crossing the line between helping with clinical decisions and causing alert fatigue. Identified reasons for alert override include alert fatigue from excessive alerts, inappropriate alerts for the clinical situation and intended prescriptions.[3] Having too many popups causes the end users to stop reading them and it could lead to major events when it matters.


  1. Allison M Miller , Maureen S Boro , Nancy E Korman , J Ben Davoren DOI Provider and pharmacist responses to warfarin drug–drug interaction alerts: a study of healthcare downstream of CPOE alerts i45-i50 First published online: 1 December 2011
  2. Grizzle AJ, Mahmood MH, Ko Y, et al. Reasons provided by prescribers when overriding drug-drug interaction alerts. Am J Manag Care 2007;13:573–8.
  3. Differences among admitting departments in alerts and alert overrides for drug-drug interaction.