Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions – A Meta-Analysis Katja M. Hakkarainen1*., Khadidja Hedna2., Max Petzold1,3, Staffan Ha¨ gg4 1 Nordic School of Public Health (NHV), Gothenburg, Sweden, 2 Laboratoire d’Enseignement et de Recherche sur le Traitement de l’Information Me´dicale, Universite´ de la Me´diterrane´, Marseille, France, 3 Centre for Applied Biostatistics, University of Gothenburg, Gothenburg, Sweden, 4 Department of Drug Research/Clinical Pharmacology, Linko¨ ping University, Linko¨ ping, Sweden Abstract Background: Numerous observational studies suggest that preventable adverse drug reactions are a significant burden in healthcare, but no meta-analysis using a standardised definition for adverse drug reactions exists. The aim of the study was to estimate the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions in adult outpatients and inpatients. Methods: Studies were identified through searching Cochrane, CINAHL, EMBASE, IPA, Medline, PsycINFO and Web of Science in September 2010, and by hand searching the reference lists of identified papers. Original peer-reviewed research articles in English that defined adverse drug reactions according to WHO’s or similar definition and assessed preventability were included. Disease or treatment specific studies were excluded. Meta-analysis on the percentage of patients with preventable adverse drug reactions and the preventability of adverse drug reactions was conducted. Results: Data were analysed from 16 original studies on outpatients with 48797 emergency visits or hospital admissions and from 8 studies involving 24128 inpatients. No studies in primary care were identified. Among adult outpatients, 2.0% (95% confidence interval (CI): 1.2–3.2%) had preventable adverse drug reactions and 52% (95% CI: 42–62%) of adverse drug reactions were preventable. Among inpatients, 1.6% (95% CI: 0.1–51%) had preventable adverse drug reactions and 45% (95% CI: 33–58%) of adverse drug reactions were preventable. Conclusions: This meta-analysis corroborates that preventable adverse drug reactions are a significant burden to healthcare among adult outpatients. Among both outpatients and inpatients, approximately half of adverse drug reactions are preventable, demonstrating that further evidence on prevention strategies is required. The percentage of patients with preventable adverse drug reactions among inpatients and in primary care is largely unknown and should be investigated in future research. Citation: Hakkarainen KM, Hedna K, Petzold M, Ha¨gg S (2012) Percentage of Patients with Preventable Adverse Drug Reactions and Preventability of Adverse Drug Reactions – A Meta-Analysis. PLoS ONE 7(3): e33236. doi:10.1371/journal.pone.0033236 Editor: Joel Joseph Gagnier, University of Michigan, United States of America Received November 22, 2011; Accepted February 3, 2012; Published March 15, 2012 Copyright: 2012 Hakkarainen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: The authors have no support or funding to report. Competing Interests: The authors have declared that no competing interests exist. * E-mail: katja.hakkarainen@nhv.se . These authors contributed equally to this work. Introduction Drug-related adverse events, including adverse drug reactions (ADRs), have been reported to be among leading causes of morbidity and mortality [1,2]. ADRs occur in both outpatients and inpatients [2-7]. In a meta-analysis in 2002, 4.9% of hospital admissions were associated with ADRs, ranging between 0.2 and 41.3% in individual studies [4]. Further, 28.9% of the ADR- related hospitalisations were considered preventable. Of inpa- tients, 10.9% is estimated to experience an ADR during hospitalisation [2]. According to the World Health Organization (WHO), costs of ADRs, including hospitalisations, surgery and lost productivity, exceed the cost of medicines in some countries [8]. As drug-related adverse events are estimated to cost USD 422– 7062 per drug-related admission and USD 2284–5640 per inpatient with drug-related adverse events (2000 values) [9], significant costs may be saved if drug-related adverse events, including ADRs, were prevented. Previous review studies have investigated preventable drug- related adverse events and the preventability of the events [4,6,10- 13]. However, most of them summarised studies on all drug- related adverse events, including adverse events due to noncom- pliance and overdose, without a clear definition for the adverse event, and used medians as summary measures [6,11-13]. Two previous reviews investigated the preventability of ADRs among outpatients being admitted to hospital [4,10], but no standardised definition for ADRs was required, outpatients without hospital- isation were not studied and no meta-analysis technique was used PLoS ONE | www.plosone.org 1 March 2012 | Volume 7 | Issue 3 | e33236