Heleen van der Sijs

Overriding of Drug Safety Alerts in Computerized Physician Order Entry

Many computerized physician order entry (CPOE) systems have integrated drug safety alerts. The authors reviewed the literature on physician response to drug safety alerts and interpreted the results using Reasons framework of accident causation. In total, 17 papers met the inclusion criteria. Drug safety alerts are overridden by clinicians in 49% to 96% of cases. Alert overriding may often be justified and adverse drug events due to overridden alerts are not always preventable. A distinction between appropriate and useful alerts should be made. The alerting system may contain error-producing conditions like low specificity, low sensitivity, unclear information content, unnecessary workflow disruptions, and unsafe and inefficient handling. These may result in active failures of the physician, like ignoring alerts, misinterpretation, and incorrect handling. Efforts to improve patient safety by increasing correct handling of drug safety alerts should focus on the error-producing conditions in software and organization. Studies on cognitive processes playing a role in overriding drug safety alerts are lacking.

Drug—drug interactions that should be non-interruptive in order to reduce alert fatigue in electronic health records

OBJECTIVE Alert fatigue represents a common problem associated with the use of clinical decision support systems in electronic health records (EHR). This problem is particularly profound with drug-drug interaction (DDI) alerts for which studies have reported override rates of approximately 90%. The objective of this study is to report consensus-based recommendations of an expert panel on DDI that can be safely made non-interruptive to the providers workflow, in EHR, in an attempt to reduce alert fatigue. METHODS We utilized an expert panel process to rate the interactions. Panelists had expertise in medicine, pharmacy, pharmacology and clinical informatics, and represented both academic institutions and vendors of medication knowledge bases and EHR. In addition, representatives from the US Food and Drug Administration and the American Society of Health-System Pharmacy contributed to the discussions. RESULTS Recommendations and considerations of the panel resulted in the creation of a list of 33 class-based low-priority DDI that do not warrant being interruptive alerts in EHR. In one institution, these accounted for 36% of the interactions displayed. DISCUSSION Development and customization of the content of medication knowledge bases that drive DDI alerting represents a resource-intensive task. Creation of a standardized list of low-priority DDI may help reduce alert fatigue across EHR. CONCLUSIONS Future efforts might include the development of a consortium to maintain this list over time. Such a list could also be used in conjunction with financial incentives tied to its adoption in EHR.

Drug safety alert generation and overriding in a large Dutch university medical centre

To evaluate numbers and types of drug safety alerts generated and overridden in a large Dutch university medical centre.

Recommendations to Improve the Usability of Drug-Drug Interaction Clinical Decision Support Alerts

OBJECTIVE To establish preferred strategies for presenting drug-drug interaction (DDI) clinical decision support alerts. MATERIALS AND METHODS A DDI Clinical Decision Support Conference Series included a workgroup consisting of 24 clinical, usability, and informatics experts representing academia, health information technology (IT) vendors, healthcare organizations, and the Office of the National Coordinator for Health IT. Workgroup members met via web-based meetings 12 times from January 2013 to February 2014, and two in-person meetings to reach consensus on recommendations to improve decision support for DDIs. We addressed three key questions: (1) what, how, where, and when do we display DDI decision support? (2) should presentation of DDI decision support vary by clinicians? and (3) how should effectiveness of DDI decision support be measured? RESULTS Our recommendations include the consistent use of terminology, visual cues, minimal text, formatting, content, and reporting standards to facilitate usability. All clinicians involved in the medication use process should be able to view DDI alerts and actions by other clinicians. Override rates are common but may not be a good measure of effectiveness. DISCUSSION Seven core elements should be included with DDI decision support. DDI information should be presented to all clinicians. Finally, in their current form, override rates have limited capability to evaluate alert effectiveness. CONCLUSION DDI clinical decision support alerts need major improvements. We provide recommendations for healthcare organizations and IT vendors to improve the clinician interface of DDI alerts, with the aim of reducing alert fatigue and improving patient safety.

On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop

BackgroundClinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority.MethodsA workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop.ResultsWe identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures.ConclusionsWe have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems.

Clinically relevant QTc prolongation due to overridden drug–drug interaction alerts: a retrospective cohort study

AIMS To investigate whether, in patients in whom drug-drug interaction (DDI) alerts on QTc prolongation were overridden, the physician had requested an electrocardiogram (ECG), and if these ECGs showed clinically relevant QTc prolongation. METHODS For all patients with overridden DDI alerts on QTc prolongation during 6 months, data on risk factors for QT prolongation, drug class and ECGs were collected from the medical record. Patients with ventricular pacemakers, patients treated on an outpatient basis, and patients using the low-risk combination of cotrimoxazole and tacrolimus were excluded. The magnitude of the effect on the QTc interval was calculated if ECGs before and after overriding were available. Changes of the QTc interval in these cases were compared with those of a control group using one QTc-prolonging drug. RESULTS In 33% of all patients with overridden QTc alerts an ECG was recorded within 1 month. ECGs were more often recorded in patients with more risk factors for QTc prolongation and with more QTc overrides. ECGs before and after the QTc override were available in 29% of patients. Thirty-one percent of patients in this group showed clinically relevant QTc prolongation with increased risk of torsades de pointes or ventricular arrhythmias. The average change in QTc interval was +31 ms for cases and -4 ms for controls. CONCLUSIONS Overriding the high-level DDI alerts on QTc prolongation rarely resulted in the preferred approach to subsequently record an ECG. If ECGs were recorded before and after QTc overrides, clinically relevant QTc prolongation was found in one-third of cases. ECG recording after overriding QTc alerts should be encouraged to prevent adverse events.

Time-dependent Drug-Drug Interaction Alerts in Care Provider Order Entry: Software May Inhibit Medication Error Reductions

Time-dependent drug-drug interactions (TDDIs) are drug combinations that result in a decreased drug effect due to coadministration of a second drug. Such interactions can be prevented by separately administering the drugs. This study attempted to reduce drug administration errors due to overridden TDDIs in a care provider order entry (CPOE) system. In four periods divided over two studies, logged TDDIs were investigated by reviewing the time intervals prescribed in the CPOE and recorded on the patient chart. The first study showed significant drug administration error reduction from 56.4 to 36.2% (p<0.05), whereas the second study was not successful (46.7 and 45.2%; p>0.05). Despite interventions, drug administration errors still occurred in more than one third of cases and prescribing errors in 79-87%. Probably the low alert specificity, the unclear alert information content, and the inability of the software to support safe and efficient TDDI alert handling all diminished correct prescribing, and consequently, insufficiently reduced drug administration errors.

An accelerated stability study of 5‐flucytosine in intravenous solution

The stability of the antimycotic drug flucytosine (5‐FC) and the extent of 5‐fluorouracil (5‐FU) formation in 5‐FC intravenous solution was studied in an accelerated stability experiment. 5‐FC intravenous solution (10 mg/ml) was heated at 40, 60, 70, 80 and 90 ∘C for a maximum of 131 days. At appropriate time intervals samples were taken and the concentrations of 5‐FC and 5‐FU were determined using a newly developed, stability indicating HPLC‐UV method. Heating the 5‐FC intravenous solution at 40, 60, 70, 80 and 90 ∘C lead to 5‐FC decomposition of respectively 0, 8.9, 14.4, 52.5 and 61.6%. The Arrhenius plot of the 5‐FC decomposition is described by: Lnk5-FC decomposition = 80.1892 * 1/T ‐ 0.2396 and the 5‐FU formation is described by Lnk5‐FU formation = ‐13087 * 1/T + 34.4028. It is concluded that 5‐FC is very stable in intravenous solution at regular storing temperatures and can therefore be stored at ambient temperatures for several years before the critical limit of 95% 5‐FC is reached. However, the toxic and teratogen degradation product 5‐FU may be present in considerable amounts in the product, due to both impurities in the raw material and the formation from 5‐FC upon sterilisation and storage.

High tobramycin serum concentrations after tobramycin inhalation in a child with renal failure

Department of Hospital Pharmacy, Erasmus University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Department of Paediatric Infectious Diseases and Immunology, Erasmus MC-Sophia Children’s Hospital, University Medical Centre, PO Box 2040, 3000 CA Rotterdam, The Netherlands; Paediatric Infectious Diseases and Immunology Department, Royal Victoria Infirmary, Great North Children’s Hospital, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK; Institute of Cellular Medicine, Newcastle University, 4th Floor, William Leech Building, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK; Paediatric Intensive Care Unit, Erasmus MC-Sophia Children’s Hospital, University Medical Centre, PO Box 2040, 3000 CA, Rotterdam, The Netherlands

Clinical reasoning in the context of active decision support during medication prescribing

OBJECTIVE Describe and analyze reasoning patterns of clinicians responding to drug-drug interaction alerts in order to understand the role of patient-specific information in the decision-making process about the risks and benefits of medication therapy. Insights could be used to inform the design of decision-support interventions. METHODS Thirty-two clinicians working with five EHRs in two countries completed sets of six medication orders each and responded to high- and low-severity drug-drug interaction alerts while verbalizing their thoughts in a standard think-aloud protocol. Tasks were recorded and analyzed to describe reasoning patterns about patient-risk assessment and strategies to avoid or mitigate it. RESULTS We observed a total of 171 prescribing decisions. Clinicians actively sought to reduce risk when responding to high-severity alerts, mostly by monitoring patients and making dose adjustments (52 alerts, 40%). In contrast, they routinely left prescriptions unchanged after low-severity alerts when they felt confident that patients would tolerate the drug combination and that treatment benefits outweighed the risks (30 alerts, 71%). Clinicians used similar reasoning patterns regardless of the EHR used and differences in alert design. DISCUSSION Clinicians conceptualized risk as a complex set of interdependent tradeoffs specific to individual patients and had a tendency not to follow advice they considered of low clinical value. Omission of patient-specific data, which was not shown in alerts or included in trigger logic, may have contributed to the constancy of reasoning and to similarities in risk-control strategies we observed despite significant differences in interface design and system function. CONCLUSION Declining an alert suggestion was preceded by sometimes brief but often complex reasoning, prioritizing different aspects of care quality and safety, especially when the perceived risk was higher. Clinicians believed that the risk indicated in drug-drug interaction alerts needs to be interpreted as one factor in the broader context of care, specific to a patient.