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National Rules for Drug–Drug Interactions: Are They Appropriate for Tertiary Hospitals?

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National Rules for Drug–Drug Interactions: Are They Appropriate for Tertiary Hospitals? ORIGINAL ARTICLE Medical Informatics https://doi.org/10.3346/jkms.2016.31.12.1887 • J Korean Med Sci 2016; 31: 1887-1896 National Rules for Drug–Drug Interactions: Are They Appropriate for Tertiary Hospitals? Insook Cho,1,2,3 Jae-Ho Lee,2,4,5 The application of appropriate rules for drug–drug interactions (DDIs) could substantially Jinwook Choi,6 Hee Hwang,7 reduce the number of adverse drug events. However, current implementations of such and David W. Bates2,3,8 rules in tertiary hospitals are problematic as physicians are receiving too many alerts, causing high override rates and alert fatigue. We investigated the potential impact of 1Nursing Department, Inha University, Incheon, Korea; 2The Center for Patient Safety Research and Korean national DDI rules in a drug utilization review program in terms of their severity Practice, Division of General Internal Medicine, coverage and the clinical efficiency of how physicians respond to them. Using lists of high- Brigham and Women’s Hospital, Boston, MA, USA; priority DDIs developed with the support of the U.S. government, we evaluated 706 3 Harvard Medical School, Boston, MA, USA; contraindicated DDI pairs released in May 2015. We evaluated clinical log data from one 4Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, tertiary hospital and prescription data from two other tertiary hospitals. The measured Seoul, Korea; 5Department of Biomedical parameters were national DDI rule coverage for high-priority DDIs, alert override rate, and Informatics, University of Ulsan College of Medicine, number of prescription pairs. The coverage rates of national DDI rules were 80% and 3.0% 6 Asan Medical Center, Seoul, Korea; Seoul National at the class and drug levels, respectively. The analysis of the system log data showed an University Hospital, Seoul, Korea; 7Seoul National University Bundang Hospital, Seongnam, Korea; overall override rate of 79.6%. Only 0.3% of all of the alerts (n = 66) were high-priority 8Partners Healthcare Systems, Wellesley, MA, USA DDI rules. These showed a lower override rate of 51.5%, which was much lower than for the overall DDI rules. We also found 342 and 80 unmatched high-priority DDI pairs which Received: 27 April 2016 were absent in national rules in inpatient orders from the other two hospitals. The national Accepted: 22 August 2016 DDI rules are not complete in terms of their coverage of severe DDIs. They also lack clinical Address for Correspondence: efficiency in tertiary settings, suggesting improved systematic approaches are needed. Jae-Ho Lee, MD Department of Emergency Medicine, University of Ulsan College of Medicine, Asan Medical Center, 88, Olympic-ro 43-gil, Keywords: Medication Safety; Drug–Drug Interactions; Prescription Alerts; Overrides; Songpa-gu, Seoul 05505, Korea Alert Fatigue E-mail: [email protected] Funding: This research was sponsored by National Research Foundation of Korea Grant, which was funded by the Korean Government (MOEHRD; No. KRF-2013R1A1A2006387). This work was also supported by grant number U19HS021094-01 from the Agency for Healthcare Research and Quality (AHRQ, Rockville, MD, USA). INTRODUCTION ing from medication errors and inappropriate drug use (3,5). The national DDI rule set was initiated and included 162 DDI A drug–drug interaction (DDI) alert is a type of medication-re- combinations and up to 706 contraindicated co-prescription lated clinical decision support function in a computerized pro- pairs as of August 2015. vider order entry (CPOE) system. These alerts provide the prom- While DDI alerts can reduce the number of DDI-related ADEs, ise of substantially reducing the number of adverse drug events alert fatigue induced by large numbers of DDI alerts can also (ADEs) by introducing automation at the time of ordering and lead to physicians ignoring clinically significant DDI alerts (2,6- by rapidly supplying usable prescribing algorithms (1). Howev- 8). A recent review of empirical analyses of CPOEs with the na- er, implementations of DDI alerts do not always provide the an- tional DDI rules found that physicians in general hospitals over- ticipated benefits. They can be very difficult to optimize, and rode a substantial fraction of automated warnings, with one alert fatigue can be a major problem if too many false-positive study finding that physicians continuing with prescription or- warnings are delivered (2). ders in 72.2% of DDI cases (9). One study of DDI alert logs re- Since December 2010, Korean hospitals have been required vealed a high override rate of 72.8% at a tertiary hospital, even to provide DDI alerts to physicians using the prospective drug the authors just considered a new alert regarding a DDI during utilization review (DUR) system run by the Health Insurance 18 months of observation period (10). Our previous examina- Review Agency (HIRA) (3-5). This DUR system aims to provide tion of DDI alert logs revealed a high override rate of 83% at a quality assurance and ensure the provision of appropriate drug tertiary hospital (8). According to a report which analyzed HIRA therapies, and it was designed to prevent potential ADEs aris- DUR data, the override rates for DDI alerts were 76.6% in 2012 © 2016 The Korean Academy of Medical Sciences. pISSN 1011-8934 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. eISSN 1598-6357 Cho I, et al. • Appropriateness of National Drug–Drug Interaction Rules and 78% in 2013 (11). Such high override rates have prompted MATERIALS AND METHODS serious concerns that physicians may be overriding or ignoring clinically important warnings, which potentially has major im- We compared the current Korean national DDI rules with the plications both for safety and physician liability. The alerts may lists of high-priority DDI rules found in previous studies (13). be unnecessarily interrupting physicians, which could threaten To identify the differences, we use a comparison framework (Fig. the provision of a consistent work process and cause inefficient 1). A retrospective observational design was used to analyze the use of time and other resources (12). alert system logs. Fig. 2 shows the study procedure, materials, In an attempt to address this problem, the present study in- measurements, and participating hospitals. We investigated data vestigated the national DDI rules using three approaches. The from three Korean hospitals: data from one hospital were used first approach involved comparing the Korean DDI rules with a for analyzing alert log data, and the data from the other two were list of the most dangerous DDIs. These lists, known as high-pri- used for analyzing prescription data. The intercountry analyses ority DDI rules, were identified by a sponsor of the Office of the compared the performance of national DDI rules in South Ko- National Coordinator for Health Information Technology in the rea with those of hospitals in three other countries. In this study USA (13,14). It is a set of 15 high-severity, clinically significant DDIs were identified for which it was advised that warnings should be generated in all electronic health record systems. The Korean National US High-priority DDI Rules (706) Rules (2,563) second approach involved investigating the DDI alert log data of a tertiary hospital to identify the rates at which high-priority DDI rules are alerted and overridden in practice. We also com- pared the results with those obtained at three hospitals in Bel- Unmatched Unmatched Matched gium, the UK, and the USA. The third approach involved exam- National High-priority Rules ining medication orders from two other hospitals in order to Rules Rules determine whether unmatched high-priority DDI rules appear in prescriptions. Based on the obtained results, we describe sev- eral areas that need further investigation in order to achieve the successful application of DDI alerts. Fig. 1. Comparison framework of the Korean national drug–drug interaction (DDI) rules and the USA high-priority DDI rules. Figure 1. Comparison framework of the Korean national drug-drug interaction (DDI) rules and the US high-priority DDI rules Hospital in Belgium Hospital in UK Hospitals Hospital in South Korea Local in US DDI Local rules DDI List of high-priority DDI rules Local DDI National DDI rules: Alert rules rules 15 class-class pairs system Alert ① ① log system (2,563 drug pairs) Rule Rule log Alert system Alert system coverage coverage ② log log Override rate National DDI rules ② National Override DUR rules rate Prescriptions: medication orders ③ Frequency of prescriptions orders Fig. 2. Study design diagram including the participating hospitals, data sources, and measurements (labeled from ① to ③). DDI = drug–drug interaction. Figure 2. Study design diagram including the participating hospitals, data sources, 1888and http://jkms.orgmeasurements (labeled from ① to ③) https://doi.org/10.3346/jkms.2016.31.12.1887 Cho I, et al. • Appropriateness of National Drug–Drug Interaction Rules we included a part of results of another study involving three of who ordered the prescriptions, the acceptance status of the alert, the authors (I.C., J.H.L., and D.W.B.) (8). and any reason(s) for overriding the alert, which were coded options or entered with free text. We collected the log data for Korean national DDI rules and lists of high-priority DDIs four consecutive months, from September 1 to December 31, in the USA 2014. The data contained 18,360 and 3,499 alert records for in- The national DDI rules were developed based on the product patient and outpatient settings, respectively. The results of a more labeling information provided by the Korea Food and Drug Ad- detailed analysis of the system log data by our team will be pre- ministration and maintained by the HIRA.
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