Reasons Provided by Prescribers When Overriding Drug-Drug Interaction Alerts

Published Online: October 01, 2007
Amy J. Grizzle, PharmD; Maysaa H. Mahmood, MS; Yu Ko, MS; John E. Murphy, PharmD; Edward P. Armstrong, PharmD; Grant H. Skrepnek, PhD; William N. Jones, MS; Gregory P. Schepers, PharmD; W. Paul Nichol, MD; Antoun Houranieh, PhD; Donna C. Dare, PharmD; Christopher T. Hoey, PharmD; and Daniel C. Malone, PhD

Objectives: To investigate prescribers’ rationales for overriding drug–drug interaction (DDI) alerts and to determine whether these reasons were helpful to pharmacists as a part of prescription order verification.

Study Design: An observational retrospective database analysis was conducted using override reasons derived from a computerized system at 6 Veterans Affairs medical centers.

Methods: Data on DDI alerts (for interactions designated as “critical” and “significant”) were obtained from ambulatory care pharmacy records from July 1, 2003, to June 30, 2004. Prescribers’ reasons for overriding alerts were organized into 14 categories and were then rated as clinically useful or not to the pharmacist in the assessment of potential patient harm.

Results: Of 291 890 overrides identified, 72% were for critical DDIs. Across the Veterans Affairs medical centers, only 20% of the override reasons for critical DDI alerts were rated as clinically useful for order verification. Despite a mandatory override reason for critical DDI alerts, 53% of the responses were “no reason provided.” The top response categories for critical and significant DDI alerts were “no reason provided,” “patient has been taking combination,” and “patient being monitored.”

Conclusions: When given the opportunity to provide a reason for overriding a DDI alert, prescribers rarely enter clinical justifications that are useful to order verification pharmacists. This brings into question how computerized physician order entry systems should be designed.

(Am J Manag Care. 2007;13:573-580)

An observational retrospective database analysis was conducted using override reasons derived from a computerized system at 6 Veterans Affairs medical centers.

Prescribers’ reasons for overriding drug–drug interaction (DDI) alerts were organized into 14 categories and were then rated as clinically useful or not to the pharmacist in the assessment of potential patient harm.

Of 291 890 overrides identified, 72% were for critical DDIs; only 20% of these override reasons were rated as clinically useful for order verification. Despite a mandatory override reason for critical DDI alerts, 53% of the responses were “no reason provided.”

Preventable adverse drug events comprise a large percentage of reported medical errors.1 An adverse drug event is defined as “an injury resulting from a medical intervention related to a drug.”2(p29) Drug–drug interactions (DDIs) are common causes of preventable adverse drug events, with 20% to 30% of adverse drug events attributed to interactions between drugs.3 The risk of DDIs compromising patient safety is substantial, and the economic burden on the healthcare system that occurs when interactions lead to patient morbidity is considerable. These problems are well documented in the literature and warrant serious investigation of possible therapeutic management strategies.1,4,5

The prescription medication use process, which can be described in general phases, includes prescribing the medication, dispensing and administering the medication, and monitoring the patient. In each step of the process, there are opportunities to prevent potentially harmful DDIs or other adverse drug events from reaching the patient. Individuals in each phase can serve as a backup safety net, particularly when information is communicated between the individuals.

Exposure to potential DDIs has been suggested as a proxy measure for medical care outcomes because of their ability to affect patients' health.6 Exposure to clinically important DDIs can be associated with a wide range of outcomes, including lack of medication efficacy, poor tolerability, and serious adverse events.7 Studies and case reports8-11 have  demonstrated that negative clinical outcomes are associated with harmful DDIs. In addition, some DDIs have been shown to lead to increased utilization of healthcare services such as higher rates of emergency department visits and hospitalizations.12-14

Delivery of care in the United States has been increasingly moving to ambulatory and outpatient settings, and several studies15-17 have been conducted to investigate the incidence of DDIs within those settings; the estimates have varied substantially among studies, ranging from 9.2% to 70.3% of patients receiving drugs with a potential DDI. When only clinically relevant DDIs are considered, the incidence drops to 1.2% to 23.3%.14,18 Prevention of exposure to potential DDIs is problematic at the prescribing end of the medication use process, as findings have shown that physicians and other prescribers fail to recognize between 37% and 47% of clinically meaningful DDIs.19

A potential solution for reducing the incidence of DDIs at the prescribing phase is the use of computerized prescriber order entry (CPOE) systems that allow prescribers to enter orders electronically.20 These systems can provide an immediate alert to a prescriber who has selected a medication that interacts with another medication the patient is receiving. However, it has been shown that physicians frequently override such alerts and that some believe that it should not be easy to override clinically important interactions.21 Other
research has found that the overrides by prescribers are generally justifiable, pointing to problems with the quality of the alerting systems.22,23 Some CPOE systems require prescribers to enter a reason if a decision is made to override an alert of clinical relevance. This can serve as a quality control aspect, while also providing information for the next steps in the medication use process. If not appropriately managed, there is a danger that CPOE alerts may be overlooked just as such alerts are in community pharmacies because of their frequency and lack of relevance.24,25 Because interacting drugs continue to reach patients, despite the systems set up to prevent them, additional information is needed to understand why prescribers override DDI alerts within existing CPOE systems.

The objective of this study was to evaluate the DDI override reasons provided by prescribers using a CPOE system at 6 Veterans Affairs medical centers (VAMCs). Specifically, the objectives of the study were (1) to determine the frequency at which physicians override DDI alerts, (2) to categorize the override reasons, and (3) to determine whether the override reasons communicated useful information to pharmacists dispensing the prescribed medication.


Data related to prescribers' reasons for overriding DDI alerts used in the VAMC system were obtained from ambulatory pharmacy dispensing records at the following 6 VAMCs: VA Ann Arbor Healthcare System, Ann Arbor, Mich; VA Boston Healthcare System, Boston, Mass; Carl T. Hayden VA Medical Center, Phoenix, Ariz; San Francisco VA Medical Center, San Francisco, Calif; VA Puget Sound Health Care System, Seattle, Wash; and Southern Arizona VA Health Care System, Tucson. The study was approved by the Humans Subjects Protection Program at the University of Arizona and by the institutional review boards and research committees at the participating VAMCs.

The override reasons were collected during a 1-year period from July 1, 2003, to June 30, 2004, for all the sites except 1. One VAMC turned off the alerting system before the beginning of the study. Once the alert system was turned on, 6 months of data were captured for this site. The data included medications involved in the DDI and the reasons provided to override the alerts. No patient-level or prescriber-level data were collected in this study.

The VA classifies 2 levels of severity for DDIs, including “critical and “significant interactions. Most of the decisions about whether an interaction is critical or significant are made at the national level by the VA Pharmacy Service. Individual VAMCs have the ability to upgrade an interaction to critical but cannot downgrade a critical interaction to significant. The VAMCs may add additional interactions to the local drug file and may make a local determination on the severity. An internal VA committee is responsible for maintaining the list of combinations that are considered to be interacting drug pairs. When the VAMC CPOE system detected that the prescriber was entering a prescription for a medication that could interact with another medication in the patient's current medication profile, a DDI alert message appeared. At this point, the prescriber could cancel the order or could override the alert and complete the prescription. Typically, providers in the VAMC system are not given the option to provide a reason for overriding significant DDIs. In some instances, individual sites can upgrade significant interactions to include an override reason response field. For critical interaction alerts, prescribers are required to document an override reason. The provider could type any message into the override reason field (free text). There were no preset responses available such as drop-down menus. Once a provider verifies that an order is desired, the order and corresponding override reason are sent to the pharmacy to be reviewed and approved.

After excluding duplicate messages for a particular DDI pair, the reasons provided by prescribers for overriding DDI alerts were organized into 14 major categories developed by the authors. These are given in Table 1. Each reason was then evaluated for its utility to the pharmacist who was responsible for evaluating each medication order (referred to as order verification) before submitting the order to the dispensing area for packaging and distribution of the pharmaceutical product to the patient. Reasons for DDI alert overrides were rated by 2 of us (AJG, MHM) as being clinically useful or not to the pharmacist for his or her assessment of the potential for patient harm before dispensing the medication. If the pharmacist rater perceived that the physician had clearly documented awareness of the potential interaction and had indicated that measures had been taken to mitigate harm, the override reason was rated as useful. Given that medical records were not used in this study, the rating was based solely on the reason provided by the prescriber.

Categorization of each override reason and grading of its utility to the pharmacist were conducted by 2 of us (AJG, MHM), who evaluated the reasons separately. The initial classifications and utility assessments were then evaluated by a third individual (YK) to identify discrepancies between results of the 2 raters. Discrepancies were discussed by the raters to reach a consensus. In situations in which no consensus was reached, override reasons were evaluated by the entire research team for classification. The research team was composed of 5 investigators (JEM, EPA, GHS, DCM, and Jacob Abarca) on the study team, all having clinical pharmacy training and experience. Interrater reliability was assessed using a ? statistic.


A total of 291 890 DDI overrides occurred during the 1-year study period (Table 2). The DDI override reasons were reviewed, and duplicate responses for a particular DDI pair were combined, leaving 15 848 unique override reasons that were assessed and categorized. The overall agreement rate between the 2 pharmacist raters in categorizing the override reasons and in determining clinical utility was almost 92% before consensus discussion. The ? statistics for the first round and for the overall agreement for clinical usefulness were 0.42 and 0.86, respectively (P < .001).

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