Background: Medication-related adverse events (MRAEs) form a large proportion of all adverse events in hospitalized patients and are associated with considerable preventable harm. Detailed information on harm related to drugs administered during hospitalization is scarce. Knowledge of the nature and preventability of MRAEs is needed to prioritize and improve medication-related patient safety.
Objective: To provide information on the nature, consequences and preventability of MRAEs occurring during hospitalization in the Netherlands.
Study Design: Analysis of MRAEs identified in a retrospective chart review of patients hospitalized during 2004.
Methods: The records of 7889 patients admitted to 21 hospitals in 2004 were reviewed by trained nurses and physicians using a three-stage process. For each hospital, patient records of 200 discharged and 200 deceased patients were randomly selected and reviewed. For each patient record, characteristics of the patient and the admission were collected. After identification of an MRAE the physician reviewers determined the type, severity, preventability, drug category and excess length of stay associated with the MRAE. Data on additional interventions or procedures related to MRAEs were obtained by linking our data to the national hospital registration database. The excess length of stay and the additional medical procedures were multiplied by unit costs to estimate the total excess direct medical costs associated with the MRAE.
Results: In total, 148 MRAEs occurred in 140 hospital admissions. The incidence of MRAEs was 0.9% (95% CI 0.7, 1.2) and the incidence of preventable MRAEs was 0.2% (95% CI 0.1, 0.4) per hospital admission. The majority of non-preventable MRAEs were adverse drug reactions caused by cancer chemotherapy. Preventable MRAEs were most often found in relation to anticoagulant treatment administered in combination with NSAIDs. Both non-preventable and preventable MRAEs resulted in considerable excess length of hospital stay and costs. On average, MRAEs resulted in an excess length of stay of 6.2 days (95% CI 3.6, 8.8) and average additional costs of €2507 (95% CI 1520, 3773).
Conclusions: This study was the first to provide detailed information on MRAEs during hospital admissions in the Netherlands, which were associated with both considerable patient harm and additional medical costs. To increase patient safety, interventions need to be developed that reduce the burden of MRAEs. These interventions should target the areas with the highest risk of MRAEs, notably antibacterials, cancer treatment, anticoagulant treatment and drug therapy in elderly patients.
Medication Error Excess Cost Computerize Physician Order Entry Hospital Discharge Register Anatomical Therapeutic Chemical Category
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.
The Dutch Patient Safety Research Program was initiated and supported by the Dutch Society of Medical Specialists (in Dutch: Orde van Medisch Specialisten) with financial support from the Ministry of Health, Welfare and Sport.
The authors have no conflicts of interest that are directly relevant to the content of this study.
Baker GR, Norton PG, Flintoft V, et al. The Canadian Adverse Events Study: the incidence of adverse events among hospital patients in Canada. CMAJ 2004; 170(11): 1678–86PubMedCrossRefGoogle Scholar
Davis P, Lay-Lee R, Briant R, et al. Adverse events in New Zealand public hospitals: I. Occurence and impact. N Z Med J 2002; 115(1167): U268Google Scholar
Wilson RM, Runciman WB, Gibberd RW, et al. The Quality in Australian Health Care Study. Med J Aust 1995 Nov 6; 163(9): 458–71PubMedGoogle Scholar
Thomas EJ, Studdert DM, Burstin HR, et al. Incidence and type of adverse events and negligent care in Utah and Colorado. Med Care 2000; 38(3): 261–71PubMedCrossRefGoogle Scholar
Zhan C, Miller MR. Excess length of stay, charges, and mortality attributable to medical injuries during hospitalization. JAMA 2003 Oct 8; 290(14): 1868–74PubMedCrossRefGoogle Scholar
Bates DW, Spell N, Cullen DJ, et al. The costs of adverse drug events in hospitalized patients. Adverse Drug Events Study Group. JAMA 1997; 277(4): 307–11PubMedCrossRefGoogle Scholar
Brennan TA, Leape LL, Laird NM, et al. Incidence of adverse events and negligence in hospitalized patients: results of the Harvard Medical Practice Study I. N Engl J Med 1991 Feb 7; 324(6): 370–6PubMedCrossRefGoogle Scholar
Hoonhout LH, de Bruijne MC, Wagner C, et al. Direct medical costs of adverse events in Dutch hospitals. BMC Health Serv Res 2009; 9 (27) [online]. Available from URL: http://www.biomedcentral.com/1472-6963/9/27 [Accessed 2010 Jul 14]
Johnson JA, Bootman JL. Drug-related morbidity and mortality: a cost-of-illness model. Arch Intern Med 1995; 155(18): 554–8CrossRefGoogle Scholar
Classen DC, Pestotnik SL, Evans RS, et al. Adverse drug event in hospitalized patients: excess length of stay, extra costs, and attributable mortality. JAMA 1997; 277(4): 301–6PubMedCrossRefGoogle Scholar
de Vries EN, Ramrattan MA, Smorenburg SM, et al. The incidence and nature of in-hospital adverse events: a systematic review. Qual Saf Health Care 2008 Jun 1; 17(3): 216–23PubMedCrossRefGoogle Scholar
Zegers M, de Bruijne MC, Wagner C, et al. Adverse events and potentially preventable deaths in Dutch hospitals: results of a retrospective patient record review study. Qual Saf Health Care 2009; 18(4): 297–302PubMedCrossRefGoogle Scholar
Runciman WB, Roughead EE, Semple SJ, et al. Adverse drug events and medication errors in Australia. Int J Qual Health Care 2003 Dec 1; 15 Suppl. 1: i49–59PubMedCrossRefGoogle Scholar
Leendertse AJ, Egberts ACG, Stoker LJ, et al., for the HARM Study Group. Frequency of and risk factors for preventable medication-related hospital admissions in the Netherlands. Arch Intern Med 2008 Sep 22; 168(17): 1890–6PubMedCrossRefGoogle Scholar
Zegers M, de Bruijne M, Wagner C, et al. Design of a retrospective patient record study on the occurrence of adverse events among patients in Dutch hospitals. BMC Health Serv Res 2007; 7 (27) [online]. Available from URL: http://www.biomedcentral.com/1472-6963/7/27 [Accessed 2010 Jul 14]
Charlson ME, Pompei P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chron Dis 1987; 40(5): 373–83 864PubMedCrossRefGoogle Scholar
Paas RA, Veenhuizen CW. Onderzoek naar de betrouwbaar-heid van de LMR. In: Rapportage voor de ziekenhuizen. Utrecht: Prismant, 2002Google Scholar
Zegers M, de Bruijne MC, Wagner C, et al. The inter-rater agreement of retrospective assessments of adverse events does not improve with two reviewers per patient record. J Clin Epidemiol 2010; 63(1): 94–102PubMedCrossRefGoogle Scholar
Altman DG. Practical statistics for medical research. London: Chapman & Hall, 1991Google Scholar
Oostenbrink JB, Bouwmans CAM, Koopmanschap MA, et al. Handbook for cost studies, methods and guidelines for economic evaluation in health care. Diemen: Health Care Insurance Council, 2004Google Scholar
Oostenbrink JB, Koopmanschap MA, Rutten FF. Standardization of costs: the Dutch manual for costing in economic evaluations. Pharmacoeconomics 2002; 20(7): 443–54PubMedCrossRefGoogle Scholar
Oostenbrink JB, Buijs-Van der Woude T, van Agthoven M, et al. Unit costs in inpatient hospital days. Pharmacoeconomics 2003; 21(4): 263–71PubMedCrossRefGoogle Scholar
Efron B, Tibshirani RJ. An introduction to the bootstrap. London: Chapman & Hall, 1993Google Scholar
Barber JA, Thompson SG. Analysis of cost data in randomized trials: an application of the non-parametric bootstrap. Stat Med 2000 Dec 15; 19(23): 3219–36PubMedCrossRefGoogle Scholar
Orser BA, Chen RJ, Yee DA. Medication errors in anesthetic practice: a survey of 687 practitioners. Can J Anaesth 2001; 48(2): 139–46PubMedCrossRefGoogle Scholar
Bates DW. Using information technology to reduce rates of medication errors in hospitals. BMJ 2000 Mar 18; 320(7237): 788–91PubMedCrossRefGoogle Scholar
van der Hooft CS, Dieleman JP, Siemes C, et al. Adverse drug reaction-related hospitalisations: a population-based cohort study. Pharmacoepidemiol Drug Saf 2008 Apr; 17(4): 365–71PubMedCrossRefGoogle Scholar
Jennings HR, Miller EC, Williams TS, et al. Reducing anticoagulant medication adverse events and avoidable patient harm. Jt Comm J Qual Patient Saf 2008 Apr; 34(4): 196–200PubMedGoogle Scholar
Kranenbuhl-Melcher A, Schlienger R, Lampert M, et al. Drug-related problems in hospitals: a review of the recent literature. Drug Safety 2007; 30(5): 379–407CrossRefGoogle Scholar
Lin HY, Liao CC, Cheng SH, et al. Association of potentially inappropriate medication use with adverse outcomes in ambulatory elderly patients with chronic diseases: experience in a Taiwanese medical setting. Drugs Aging 2008; 25(1): 49–59PubMedCrossRefGoogle Scholar
Fischhoff B. Hindsight ≠ foresight: the effect of outcome knowledge on judgement under uncertainty. J Exp Psychol Hum Percept Perf 1975; 1: 288–99CrossRefGoogle Scholar
Rigby K, Clark RB, Runciman WB. Adverse events in health care: setting priorities based on economic evaluations. J Qual Clin Pract 1999; 19(1): 7–12PubMedCrossRefGoogle Scholar
Yu KH, Nation RL, Dooley MJ. Multiplicity of medication safety terms, definitions and functional meanings: when is enough enough? Qual Saf Health Care 2005; 14(5): 358–63PubMedCrossRefGoogle Scholar
Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 1998 Apr 15; 279(15): 1200–5PubMedCrossRefGoogle Scholar
Suh DC, Woodall BS, Shin SK, et al. Clinical and economical impact of adverse drug reactions in hospitalized patients. Ann Pharmacother 2007; 34: 1373–9Google Scholar
Leape LL, Brennan TA, Laird N, et al. The nature of adverse events in hospitalized patients: results of the Harvard Medical Practice Study II. N Engl J Med 1991 Feb 7; 324(6): 377–84PubMedCrossRefGoogle Scholar
Bates DW, Cullen D, Laird N, et al. Incidence of adverse drug events and potential adverse drug events: implication for prevention. JAMA 1995 Jul 5; 274(1): 29–34PubMedCrossRefGoogle Scholar
Eslami S, Keizer de N, Abu-Hanna A. The impact of computerized physician medication order entry in hospitalized patients: a systematic review. Int J Med Inform 2008; 77(6): 365–76PubMedCrossRefGoogle Scholar
Rozich JD, Haraden CR, Resar RK. Adverse drug event trigger tool: a practical methodology for measuring medication related harm. Qual Saf Health Care 2003 Jun 1; 12(3): 194–200PubMedCrossRefGoogle Scholar
Poon EG, Cina JL, Churchill W, et al. Medication dispensing errors and potential adverse drug events before and after implementing bar code technology in the pharmacy. Ann Intern Med 2007; 145: 426–34Google Scholar
Dormann H, Muth-Selbach U, Krebs S, et al. Incidence and costs of adverse drug reactions during hospitalization: computerised monitoring versus spontaneous reporting. Drug Saf 2000; 22(2): 161–8PubMedCrossRefGoogle Scholar
Brown M, Frost R, Ko Y, et al. Diagramming patients’ views of root causes of adverse drug events in ambulatory care: an online tool for planning education and research. Patient Educ Couns 2006; 62: 302–15PubMedCrossRefGoogle Scholar
Knudsen P, Herborg H, Mortensen AR, et al. Preventing medication errors in community pharmacy: root-cause analysis of transcription errors. Qual Saf Health Care 2007 Aug 1; 16(4): 285–90PubMedCrossRefGoogle Scholar
Karnon J, McIntosh A, Dean J, et al. Modelling the expected net benefits of interventions to reduce the burden of medication errors. J Health Serv Res Policy 2008 Apr 1; 13(2): 85–91PubMedCrossRefGoogle Scholar
van den Bemt PMLA, Postma MJ, van Roon EN, et al. Cost-benefit analysis of the detection of prescribing errors by hospital pharmacy staff. Drug Saf 2002; 25(2): 135–43PubMedCrossRefGoogle Scholar
Bobb A, Gleason K, Husch M, et al. The epidemiology of prescribing errors: the potential impact of computerized prescriber order entry. Arch Intern Med 2004; 164(7): 785–92PubMedCrossRefGoogle Scholar
Markert A, Thierry V, Kleber M, et al. Chemotherapy safety and severe adverse events in cancer patients: strategies to efficiently avoid chemotherapy errors in in- and outpatient treatment. Int J Cancer 2009 Feb 1; 124(3): 722–8PubMedCrossRefGoogle Scholar
Riechelmann RP, Tannock IF, Wang L, et al. Potential drug interactions and duplicate prescriptions among cancer patients. J Natl Cancer Inst 2007 Apr 18; 99(8): 592–600PubMedCrossRefGoogle Scholar