European Journal of Clinical Pharmacology

, Volume 74, Issue 4, pp 389–404 | Cite as

Categorization and association analysis of risk factors for adverse drug events

  • Lina ZhouEmail author
  • Anamika Paul Rupa



Adverse drug events (ADE) are among the leading causes of morbidity and hospitalization. This review analyzes risk factors for ADE, particularly their categorizations and association patterns, the prevalence, severity, and preventability of ADE, and method characteristics of reviewed studies.


Literature search was conducted via PubMed, Science Direct, CINAHL, and MEDLINE. A review was conducted of research articles that reported original data about specific risk factors for ADE since 2000. Data analyses were performed using Excel and R.


We summarized 211 risk factors for ADE, and grouped them into five main categories: patient-, disease-, medication-, health service-, and genetics-related. Among them, medication- and disease-related risk factors were most frequently studied. We further classified risk factors within each main category into subtypes. Among them, polypharmacy, age, gender, central nervous system agents, comorbidity, service utilization, inappropriate use/change use of drugs, cardiovascular agents, and anti-infectives were most studied subtypes. An association analysis of risk factors uncovered many interesting patterns. The median prevalence, preventability, and severity rate of reported ADE was 19.5% (0.29%~86.2%), 36.2% (2.63%~91%), and 16% (0.01%~47.4%), respectively.


This review introduced new categories and subtypes of risk factors for ADE. The broad and in-depth coverage of risk factors and their association patterns elucidate the complexity of risk factor analysis. Managing risk factors for ADE is crucial for improving patient safety, particularly for the elderly, comorbid, and polypharmacy patients. Some under-explored risk factors such as genetics, mental health and wellness, education, lifestyle, and physical environment invite future research.


Adverse drug events Risk factor Categorization Association analysis 



The authors would like to thank one reviewer for her assistance in annotating a subset of research articles. The authors would also like to thank another reviewer who provided consultation for several subtypes of risk factors.

Authors’ contributions

LZ: data annotation and categorization; idea conceiving and study design; analysis and interpretation of the data; and preparation, review, revisions, and approval of the manuscript. AR: collection, management, annotation, analysis, and interpretation of the data; and preparation, revisions, and approval of the manuscript.

Compliance with ethical standards

Conflicts of interest

The authors declare that they have no conflict of interest.

Supplementary material

228_2017_2373_MOESM1_ESM.docx (196 kb)
ESM 1 (DOCX 196 kb)


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© Springer-Verlag GmbH Germany, part of Springer Nature 2017

Authors and Affiliations

  1. 1.University of Maryland, Baltimore CountyBaltimoreUSA

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