Design: Chart review was performed on a stratified random subset of all allergy alerts occurring during a 3-month period (August through October 2002) at a large academic hospital.

Measurements: Factors that were measured were drug/allergy combinations that triggered alerts, frequency of specific override reasons, characteristics of ADEs, and completeness of allergy documentation.

Results: A total of 6,182 (80%) of 7,761 alerts were overridden in 1,150 patients. In this sample, only 10% of alerts were triggered by an exact match between the drug ordered and allergy listed. Physicians' most common reasons for overriding alerts were “Aware/Will monitor” (55%), “Patient does not have this allergy/tolerates” (33%), and “Patient taking already” (10%). In a stratified random subset of 320 patients (28% of 1,150) on chart review, 19 (6%) experienced ADEs attributed to the overridden drug; of these, 9 (47%) were serious. None of the ADEs was considered preventable, because the overrides were deemed clinically justifiable. The degree of completeness of patients' allergy lists was highly variable and generally low in both paper charts and the CPOE system.

Drug allergy alerting represents a particularly important part of decision support.^5,12,13 Even though only about 20% of patients react when they receive medications to which they have “known allergies,” the reactions can be devastating when they occur.¹⁴ It should be possible to develop tools to warn providers reliably when the patient has had a prior reaction to a medication, whether an allergy (immune-mediated type I hypersensitivity reaction), or a sensitivity (adverse drug reaction that is non–immune-mediated, e.g., nausea or diarrhea). In CPOE applications that maintain patients' medication and allergy lists, ordered drugs can be checked against the patient's allergy list, and decision support can generate alerts that warn the physician of a possible allergy to the ordered drug. Physicians can either accept or override these alerts.

The challenge of ensuring that allergy alerting functions well stems from a number of factors. Maintaining accurate allergy lists can be difficult because there may not be clear distinctions between allergies and sensitivities, and there is no general consensus on whether both should be included in allergy lists. In addition, neither the specificity of alerting algorithms nor the relative effectiveness of different methods of alerting (e.g., alerts that interrupt workflow vs. those that display information, but do not interrupt) has been elucidated fully. A study by Abookire et al.¹⁶ found that nearly 80% of drug allergy alerts at Brigham and Women's Hospital were overridden by physicians, and Payne et al.¹⁷ found a 69% override rate at the Veterans Administration Puget Sound Health Care System in Seattle, WA. One reason cited for these high override rates was highly inclusive drug-class and drug cross-reactivity mapping, which generated a large number of allergy alerts for drugs with only slight potential to cause an allergic reaction (e.g., furosemide ordered in the context of an allergy to sulfa antibiotics). Policies requiring physicians to renew certain drugs for the same patient multiple times, causing many redundant alerts to be generated, also were cited. However, neither of these studies addressed the clinical consequences of allergy alerts that were overridden, such as adverse drug events (ADEs).

An excess of allergy alerts with low predictive value for allergic drug reactions and of alerts that are potentially inaccurate because of inconsistent information in the medical record, has the potential to erode physicians' faith in allergy alerts and to increase the likelihood that alerts containing important information will be ignored.¹⁵ However, failing to warn could also have deleterious consequences. Continuous quality improvement to ensure appropriate alerting is critical for continued efficacy and acceptance of CPOE decision support. Therefore, our goals were: (1) to characterize overridden drug allergy alerts in more detail; (2) to assess how often overriding allergy alerts leads to preventable ADEs in the inpatient setting; and (3) to suggest methods for improving drug allergy alerting systems.

The 80% override rate of drug allergy alerts in this study was similar to the override rate previously found in the same hospital and CPOE system by Abookire et al.¹⁶ and somewhat lower than the 91% override rate found at five adult primary care practices by Weingart et al.²⁴ In both of those studies, the high override rates were partly attributed to alerting protocols that generated alerts as long as the ordered drug was in the same family as a drug on the patient's allergy list. We also found that the majority (90%) of overrides occurred when the two drugs belonged to the same family but were not identical (for example, codeine and hydromorphone).

The current design of our allergy-alerting protocol uses a commercial medication knowledge base to create groupings of medications that may have similar allergenic properties. In many cases, the clinical relevance of the relationships is inferred from pharmacologic or structural similarity and not from clinical data. In these instances, the likelihood of a patient's suffering from an adverse consequence from the administration of a related drug is low (e.g., if a patient with codeine sensitivity takes morphine). As more clinical data are gathered, this information should be incorporated into allergy checking rule bases, but in the absence of such data, health care institutions will need to make their own decisions about whether to alert for medications that are nonexact matches to the documented allergy.

In this study, we found that when “allergies” to specific narcotics were documented in the patient's allergy list, nausea and vomiting were the most common reactions noted. In fact, symptoms such as nausea, vomiting, respiratory depression, and constipation are not true allergic reactions, but rather direct side effects of, or sensitivities to, the narcotics' pharmacologic activity.²⁵ Although allergic, anaphylactic, and anaphylactoid (pseudo-allergic, non–immune-mediated reaction resulting in basophil or mast cell activation and release of vasoactive mediators) reactions to narcotics have been reported, such reactions are rare.^26,27 Furthermore, an individual patient's responses may be very different to various narcotics, and several different physiologic variables can affect a patient's sensitivity to narcotics at a given time.²⁷ Therefore, instead of frequently alerting about possible “allergies” to ordered narcotics whenever nonexact drug/allergy matches arise, we would recommend generating an alert only when the ordered drug is an exact match to (i.e., is identical to) the drug on the allergy list, and in the case of nonexact matches, to simply display the previously documented reaction in an informative but noninterruptive manner. Such noninterruptive alerts could advise increased monitoring or early use of premedications to attempt to ameliorate symptoms when they occur. In addition, better ways to differentiate true allergies from sensitivities when documenting “allergy lists” in CPOE should be explored.

The protocol for sulfa-allergy alerting can also be improved substantially. We found that when sulfonamide-containing diuretics, such as furosemide, were ordered, most allergy alerts were triggered by a documented allergy to “sulfa”—a term that typically denotes sulfonamide antibiotic, such as sulfamethoxazole. However, the weight of evidence from chemical–structural and clinical studies strongly suggests that immunologic cross-reactivity between sulfonamide antibiotics and sulfonamide nonantibiotics (such as furosemide, hydrochlorothiazide, glyburide, and celecoxib) is unlikely and that patients with a history of allergic reaction to a sulfonamide antibiotic were no more likely to have a subsequent allergic reaction to a different sulfonamide than to a nonsulfonamide, such as penicillin.^{28,29,30,31,32} Thus, we recommend that no allergy alert should be generated when clinicians order sulfonamide nonantibiotics in the context of a documented “sulfa” (sulfonamide antibiotic) allergy. Alternatively, any alerts that are generated should be noninterruptive and simply warn the clinician that the patient may have a generally increased propensity to developing allergic reactions.

We also examined the reasons given by physicians for overriding drug allergy alerts and the clinical consequences of such override actions. The fact that half of the override reasons were “Aware/Will monitor” reflects the complex calculus involved in the risk–benefit analysis of therapeutic decision making, particularly with nonexact match allergy alerts. Such decisions must weigh the need to treat with a particular drug (e.g., need for pain relief) against the likelihood, type, and severity of a possible adverse reaction (e.g., life-threatening anaphylaxis vs. mild nausea).²⁵

Another common reason given was “Patient does not have this allergy/Tolerates,” accounting for nearly a third of overrides. The high incidence of this override reason suggests that physicians may often be using the patient's self-report or other information at the time of visit to determine if a patient will tolerate the medication. Other significant contributing factors to the use of this override option may be the infrequent updating of patients' allergy lists, resulting in many lists' being out of date or inaccurate, and the numerous locations where allergies are documented in the chart, often with little agreement. Improving the maintenance of patients' allergy lists could be accomplished by having clinicians select override reasons from a menu of choices; selection of reasons such as “Patient does not have this allergy/Tolerates” or “Patient taking already” from the menu would automatically prompt the clinician to remove the drug from the allergy list. Electronic medical records linked to CPOE could create the ability to maintain a single allergy list, rather than the numerous ones that exist today.

We feel it is reasonable to require input of the override reason, which enables pharmacists and nurses downstream in the medication order process to see not only that the ordering physician has considered the risk of drug allergy but also understand the reason why the physician felt it was safe to override the alert. Furthermore, modifying the override reason field so that physicians pick from a menu of choices enables automatic updating of the patient's allergy history—if the reason chosen is, for example, that the patient tolerates the drug well or is already taking the medication at home. Finally, the override reasons provide information that help us better understand why certain alerts are not accepted, and therefore to potentially modify the alerting strategy. This study shows the importance of analyzing override reasons as a quality improvement tool to improve alerting strategies, and organizations should consider making this part of their routine improvement processes after implementing CPOE.

Of the overrides of alerts in the stratified random subset based on nonexact drug/allergy matches, only 6% resulted in an adverse drug event, and none of these ADEs was preventable, since all of the overrides appeared clinically justifiable. Thus, the high override rate appears to be attributable primarily to excessive and inappropriate alerting, rather than to poor clinical judgment or to clinician disregard for allergy alerting. Weingart et al.²⁴ similarly found ADEs resulting from overridden alerts to be infrequent (none in a subset of 31 overridden alerts resulted in an ADE), and reviewers in that study agreed with the prescriber's override decision in almost every case (65 of 68 overrides). Results of these studies suggest that decreasing alerting of nonexact drug/allergy matches should be a safe strategy to reduce overalerting. The fact that the majority of ADEs in this study were narcotic-induced nausea or vomiting, which are not true allergic reactions, lends further support to this notion. Reducing overalerting is important because too-frequent false alerts to safety hazards not only waste clinicians' time, but also may cause truly important warnings to be overlooked or ignored. We have listed our recommended strategies for improving allergy alerting in .

Limitations of this study include that the study period was short and the sample of medication orders analyzed was small compared with the total number entered into the CPOE system each year. In addition, the rate of ADEs owing to administering alerted drugs may be overestimated since we did not use a control group to measure the baseline rate of ADEs resulting from nonalerted drug orders. Given the complex medical regimens and types of diseases in our patient population, it was difficult to determine whether ADEs were caused by the overridden drugs or to other drugs or the patients' disease states. Furthermore, the accuracy of the two-physician panel's judgments as to the justifiability of the physicians' overrides was reliant on the thoroughness of documentation in the patients' charts. Finally, this study was conducted within a single CPOE system, so the rates of overrides and ADEs may not be generalizable, although we feel that many of the lessons learned will be applicable to allergy alerting in other systems.