Skip to main content
Top
Published in: BMC Medical Informatics and Decision Making 1/2019

Open Access 01-12-2019 | Fatigue | Study protocol

The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: protocol for a cluster randomized stepped-wedge trial

Authors: T. Bakker, J. E. Klopotowska, S. Eslami, D. W. de Lange, R. van Marum, H. van der Sijs, E. de Jonge, D. A. Dongelmans, N. F. de Keizer, A. Abu-Hanna

Published in: BMC Medical Informatics and Decision Making | Issue 1/2019

Login to get access

Abstract

Background

Drug-drug interactions (DDIs) can cause patient harm. Between 46 and 90% of patients admitted to the Intensive Care Unit (ICU) are exposed to potential DDIs (pDDIs). This rate is twice as high as patients on general wards. Clinical decision support systems (CDSSs) have shown their potential to prevent pDDIs. However, the literature shows that there is considerable room for improvement of CDSSs, in particular by increasing the clinical relevance of the pDDI alerts they generate and thereby reducing alert fatigue. However, consensus on which pDDIs are clinically relevant in the ICU setting is lacking. The primary aim of this study is to evaluate the effect of alerts based on only clinically relevant interactions for the ICU setting on the prevention of pDDIs among Dutch ICUs.

Methods

To define the clinically relevant pDDIs, we will follow a rigorous two-step Delphi procedure in which a national expert panel will assess which pDDIs are perceived clinically relevant for the Dutch ICU setting. The intervention is the CDSS that generates alerts based on the clinically relevant pDDIs. The intervention will be evaluated in a stepped-wedge trial. A total of 12 Dutch adult ICUs using the same patient data management system, in which the CDSS will operate, were invited to participate in the trial. Of the 12 ICUs, 9 agreed to participate and will be enrolled in the trial. Our primary outcome measure is the incidence of clinically relevant pDDIs per 1000 medication administrations.

Discussion

This study will identify pDDIs relevant for the ICU setting. It will also enhance our understanding of the effectiveness of alerts confined to clinically relevant pDDIs. Both of these contributions can facilitate the successful implementation of CDSSs in the ICU and in other domains as well.

Trial registration

Nederlands Trial register Identifier: NL6762. Registered November 26, 2018.
Literature
1.
go back to reference Krahenbuhl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krahenbuhl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf. 2007;30(5):379–407.CrossRef Krahenbuhl-Melcher A, Schlienger R, Lampert M, Haschke M, Drewe J, Krahenbuhl S. Drug-related problems in hospitals: a review of the recent literature. Drug Saf. 2007;30(5):379–407.CrossRef
2.
go back to reference Reis AM, Cassiani SH. Adverse drug events in an intensive care unit of a university hospital. Eur J Clin Pharmacol. 2011;67(6):625–32.CrossRef Reis AM, Cassiani SH. Adverse drug events in an intensive care unit of a university hospital. Eur J Clin Pharmacol. 2011;67(6):625–32.CrossRef
3.
go back to reference Kane-Gill SL, Dasta JF, Buckley MS, Devabhakthuni S, Liu M, Cohen H, et al. Clinical practice guideline: safe medication use in the ICU. Crit Care Med. 2017;45(9):e877–915.CrossRef Kane-Gill SL, Dasta JF, Buckley MS, Devabhakthuni S, Liu M, Cohen H, et al. Clinical practice guideline: safe medication use in the ICU. Crit Care Med. 2017;45(9):e877–915.CrossRef
4.
go back to reference Hennessy S, Leonard CE, Gagne JJ, Flory JH, Han X, Brensinger CM, et al. Pharmacoepidemiologic methods for studying the health effects of drug-drug interactions. Clin Pharmacol Ther. 2016;99(1):92–100.CrossRef Hennessy S, Leonard CE, Gagne JJ, Flory JH, Han X, Brensinger CM, et al. Pharmacoepidemiologic methods for studying the health effects of drug-drug interactions. Clin Pharmacol Ther. 2016;99(1):92–100.CrossRef
5.
go back to reference Zheng WY, Richardson LC, Li L, Day RO, Westbrook JI, Baysari MT. Drug-drug interactions and their harmful effects in hospitalised patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2018;74(1):15–27.CrossRef Zheng WY, Richardson LC, Li L, Day RO, Westbrook JI, Baysari MT. Drug-drug interactions and their harmful effects in hospitalised patients: a systematic review and meta-analysis. Eur J Clin Pharmacol. 2018;74(1):15–27.CrossRef
6.
go back to reference Zwart-van Rijkom JE, Uijtendaal EV, ten Berg MJ, van Solinge WW, Egberts AC. Frequency and nature of drug-drug interactions in a Dutch university hospital. Br J Clin Pharmacol. 2009;68(2):187–93.CrossRef Zwart-van Rijkom JE, Uijtendaal EV, ten Berg MJ, van Solinge WW, Egberts AC. Frequency and nature of drug-drug interactions in a Dutch university hospital. Br J Clin Pharmacol. 2009;68(2):187–93.CrossRef
7.
go back to reference Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med. 1997;25(8):1289–97.CrossRef Cullen DJ, Sweitzer BJ, Bates DW, Burdick E, Edmondson A, Leape LL. Preventable adverse drug events in hospitalized patients: a comparative study of intensive care and general care units. Crit Care Med. 1997;25(8):1289–97.CrossRef
8.
go back to reference Uijtendaal EV, van Harssel LL, Hugenholtz GW, Kuck EM, Zwart-van Rijkom JE, Cremer OL, et al. Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy. 2014;34(3):213–9.CrossRef Uijtendaal EV, van Harssel LL, Hugenholtz GW, Kuck EM, Zwart-van Rijkom JE, Cremer OL, et al. Analysis of potential drug-drug interactions in medical intensive care unit patients. Pharmacotherapy. 2014;34(3):213–9.CrossRef
9.
go back to reference Nabovati E, Vakili-Arki H, Taherzadeh Z, Saberi MR, Medlock S, Abu-Hanna A, et al. Information technology-based interventions to improve drug-drug interaction outcomes: a systematic review on features and effects. J Med Syst. 2017;41(1):12.CrossRef Nabovati E, Vakili-Arki H, Taherzadeh Z, Saberi MR, Medlock S, Abu-Hanna A, et al. Information technology-based interventions to improve drug-drug interaction outcomes: a systematic review on features and effects. J Med Syst. 2017;41(1):12.CrossRef
10.
go back to reference Smithburger PL, Buckley MS, Bejian S, Burenheide K, Kane-Gill SL. A critical evaluation of clinical decision support for the detection of drug-drug interactions. Expert Opin Drug Saf. 2011;10(6):871–82.CrossRef Smithburger PL, Buckley MS, Bejian S, Burenheide K, Kane-Gill SL. A critical evaluation of clinical decision support for the detection of drug-drug interactions. Expert Opin Drug Saf. 2011;10(6):871–82.CrossRef
11.
go back to reference Jaspers MW, Smeulers M, Vermeulen H, Peute LW. Effects of clinical decision-support systems on practitioner performance and patient outcomes: a synthesis of high-quality systematic review findings. J Am Med Inform Assoc. 2011;18(3):327–34.CrossRef Jaspers MW, Smeulers M, Vermeulen H, Peute LW. Effects of clinical decision-support systems on practitioner performance and patient outcomes: a synthesis of high-quality systematic review findings. J Am Med Inform Assoc. 2011;18(3):327–34.CrossRef
12.
go back to reference Tolley CL, Slight SP, Husband AK, Watson N, Bates DW. Improving medication-related clinical decision support. Am J Health Syst Pharm. 2018;75(4):239–46.CrossRef Tolley CL, Slight SP, Husband AK, Watson N, Bates DW. Improving medication-related clinical decision support. Am J Health Syst Pharm. 2018;75(4):239–46.CrossRef
13.
go back to reference Coleman JJ, van der Sijs H, Haefeli WE, Slight SP, McDowell SE, Seidling HM, et al. On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop. BMC Med Inform Decis Mak. 2013;13:111.CrossRef Coleman JJ, van der Sijs H, Haefeli WE, Slight SP, McDowell SE, Seidling HM, et al. On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop. BMC Med Inform Decis Mak. 2013;13:111.CrossRef
14.
go back to reference Payne TH, Hines LE, Chan RC, Hartman S, Kapusnik-Uner J, Russ AL, et al. Recommendations to improve the usability of drug-drug interaction clinical decision support alerts. J Am Med Inform Assoc. 2015;22(6):1243–50.CrossRef Payne TH, Hines LE, Chan RC, Hartman S, Kapusnik-Uner J, Russ AL, et al. Recommendations to improve the usability of drug-drug interaction clinical decision support alerts. J Am Med Inform Assoc. 2015;22(6):1243–50.CrossRef
15.
go back to reference Fung KW, Kapusnik-Uner J, Cunningham J, Higby-Baker S, Bodenreider O. Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support. J Am Med Inform Assoc. 2017;24(4):806–12.CrossRef Fung KW, Kapusnik-Uner J, Cunningham J, Higby-Baker S, Bodenreider O. Comparison of three commercial knowledge bases for detection of drug-drug interactions in clinical decision support. J Am Med Inform Assoc. 2017;24(4):806–12.CrossRef
16.
go back to reference van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc. 2006;13(2):138–47.CrossRef van der Sijs H, Aarts J, Vulto A, Berg M. Overriding of drug safety alerts in computerized physician order entry. J Am Med Inform Assoc. 2006;13(2):138–47.CrossRef
17.
go back to reference Wong A, Amato MG, Seger DL, Slight SP, Beeler PE, Dykes PC, et al. Evaluation of medication-related clinical decision support alert overrides in the intensive care unit. J Crit Care. 2017;39:156–61.CrossRef Wong A, Amato MG, Seger DL, Slight SP, Beeler PE, Dykes PC, et al. Evaluation of medication-related clinical decision support alert overrides in the intensive care unit. J Crit Care. 2017;39:156–61.CrossRef
18.
go back to reference Papadopoulos J, Smithburger PL. Common drug interactions leading to adverse drug events in the intensive care unit: management and pharmacokinetic considerations. Crit Care Med. 2010;38(6 Suppl):S126–35.CrossRef Papadopoulos J, Smithburger PL. Common drug interactions leading to adverse drug events in the intensive care unit: management and pharmacokinetic considerations. Crit Care Med. 2010;38(6 Suppl):S126–35.CrossRef
19.
go back to reference Peterson JF, Bates DW. Preventable medication errors: identifying and eliminating serious drug interactions. J Am Pharm Assoc (Washington,DC : 1996). 2001;41(2):159–60.CrossRef Peterson JF, Bates DW. Preventable medication errors: identifying and eliminating serious drug interactions. J Am Pharm Assoc (Washington,DC : 1996). 2001;41(2):159–60.CrossRef
20.
go back to reference van der Sijs H. Drug safety alerting in computerized physician order entry unraveling and counteracting alert fatigue: Erasmus Universteit Rotterdam; 2009. van der Sijs H. Drug safety alerting in computerized physician order entry unraveling and counteracting alert fatigue: Erasmus Universteit Rotterdam; 2009.
21.
go back to reference Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC Med Res Methodol. 2006;6:54.CrossRef Brown CA, Lilford RJ. The stepped wedge trial design: a systematic review. BMC Med Res Methodol. 2006;6:54.CrossRef
22.
go back to reference Ellenberg SS. The stepped-wedge clinical trial: evaluation by rolling deployment. Jama. 2018;319(6):607–8.CrossRef Ellenberg SS. The stepped-wedge clinical trial: evaluation by rolling deployment. Jama. 2018;319(6):607–8.CrossRef
23.
go back to reference Hemming K, Lilford R, Girling AJ. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs. Stat Med. 2015;34(2):181–96.CrossRef Hemming K, Lilford R, Girling AJ. Stepped-wedge cluster randomised controlled trials: a generic framework including parallel and multiple-level designs. Stat Med. 2015;34(2):181–96.CrossRef
24.
go back to reference Hargreaves JR, Prost A, Fielding KL, Copas AJ. How important is randomisation in a stepped wedge trial? Trials. 2015;16:359.CrossRef Hargreaves JR, Prost A, Fielding KL, Copas AJ. How important is randomisation in a stepped wedge trial? Trials. 2015;16:359.CrossRef
25.
go back to reference Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krle AJK, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Revista panamericana de salud publica =. Pan Am J Public Health. 2015;38(6):506–14. Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gotzsche PC, Krle AJK, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Revista panamericana de salud publica =. Pan Am J Public Health. 2015;38(6):506–14.
26.
go back to reference Hemming K, Taljaard M, McKenzie JE, Hooper R, Copas A, Thompson JA, et al. Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration. Bmj. 2018;363:k1614.CrossRef Hemming K, Taljaard M, McKenzie JE, Hooper R, Copas A, Thompson JA, et al. Reporting of stepped wedge cluster randomised trials: extension of the CONSORT 2010 statement with explanation and elaboration. Bmj. 2018;363:k1614.CrossRef
27.
go back to reference van de Klundert N, Holman R, Dongelmans DA, de Keizer NF. Data Resource Profile: the Dutch National Intensive Care Evaluation (NICE) Registry of Admissions to Adult Intensive Care Units. Int J Epidemiol. 2015;44(6):1850-h.CrossRef van de Klundert N, Holman R, Dongelmans DA, de Keizer NF. Data Resource Profile: the Dutch National Intensive Care Evaluation (NICE) Registry of Admissions to Adult Intensive Care Units. Int J Epidemiol. 2015;44(6):1850-h.CrossRef
29.
go back to reference Fitch, Kathryn, Steven J. Bernstein, Maria Dolores Aguilar, Bernard Burnand, Juan Ramon LaCalle, Pablo Lazaro, Mirjam van het Loo, Joseph McDonnell, Janneke Vader, and James P. Kahan, The RAND/UCLA Appropriateness Method User's Manual. Santa Monica, CA: RAND Corporation, 2001. Available at: https://www.rand.org/pubs/monograph_reports/MR1269.html, visited at 2018-11-29. Fitch, Kathryn, Steven J. Bernstein, Maria Dolores Aguilar, Bernard Burnand, Juan Ramon LaCalle, Pablo Lazaro, Mirjam van het Loo, Joseph McDonnell, Janneke Vader, and James P. Kahan, The RAND/UCLA Appropriateness Method User's Manual. Santa Monica, CA: RAND Corporation, 2001. Available at: https://​www.​rand.​org/​pubs/​monograph_​reports/​MR1269.​html, visited at 2018-11-29.
30.
go back to reference Kilsdonk E, Peute LW, Jaspers MW. Factors influencing implementation success of guideline-based clinical decision support systems: a systematic review and gaps analysis. Int J Med Inform. 2017;98:56–64.CrossRef Kilsdonk E, Peute LW, Jaspers MW. Factors influencing implementation success of guideline-based clinical decision support systems: a systematic review and gaps analysis. Int J Med Inform. 2017;98:56–64.CrossRef
31.
go back to reference Rozich JD, Haraden CR, Resar RK. Adverse drug event trigger tool: a practical methodology for measuring medication related harm. Qual Saf Health Care. 2003;12(3):194–200.CrossRef Rozich JD, Haraden CR, Resar RK. Adverse drug event trigger tool: a practical methodology for measuring medication related harm. Qual Saf Health Care. 2003;12(3):194–200.CrossRef
32.
go back to reference Vanham D, Spinewine A, Hantson P, Wittebole X, Wouters D, Sneyers B. Drug-drug interactions in the intensive care unit: do they really matter? J Crit Care. 2017;38:97–103.CrossRef Vanham D, Spinewine A, Hantson P, Wittebole X, Wouters D, Sneyers B. Drug-drug interactions in the intensive care unit: do they really matter? J Crit Care. 2017;38:97–103.CrossRef
33.
go back to reference Trivedi MH, Kern JK, Marcee A, Grannemann B, Kleiber B, Bettinger T, et al. Development and implementation of computerized clinical guidelines: barriers and solutions. Methods Inf Med. 2002;41(5):435–42.CrossRef Trivedi MH, Kern JK, Marcee A, Grannemann B, Kleiber B, Bettinger T, et al. Development and implementation of computerized clinical guidelines: barriers and solutions. Methods Inf Med. 2002;41(5):435–42.CrossRef
34.
go back to reference Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved. Int J Pharm Pract. 2012;20(6):402–8.CrossRef Smithburger PL, Kane-Gill SL, Seybert AL. Drug-drug interactions in the medical intensive care unit: an assessment of frequency, severity and the medications involved. Int J Pharm Pract. 2012;20(6):402–8.CrossRef
Metadata
Title
The effect of ICU-tailored drug-drug interaction alerts on medication prescribing and monitoring: protocol for a cluster randomized stepped-wedge trial
Authors
T. Bakker
J. E. Klopotowska
S. Eslami
D. W. de Lange
R. van Marum
H. van der Sijs
E. de Jonge
D. A. Dongelmans
N. F. de Keizer
A. Abu-Hanna
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Fatigue
Published in
BMC Medical Informatics and Decision Making / Issue 1/2019
Electronic ISSN: 1472-6947
DOI
https://doi.org/10.1186/s12911-019-0888-7

Other articles of this Issue 1/2019

BMC Medical Informatics and Decision Making 1/2019 Go to the issue