Frequency of adverse drug reactions in hospitalized patients: a systematic review and meta-analysis

Pharmacoepidemiol Drug Saf. 2012 Nov;21(11):1139-54. doi: 10.1002/pds.3309. Epub 2012 Jul 4.


Purposes: To perform a comprehensive systematic review of prospective studies about frequency of adverse drug reactions (ADRs) occurring during hospitalization (ADR(In) ), including a thorough study quality assessment, meta-analysis and heterogeneity evaluation.

Methods: Systematic review of several databases: Pubmed, EMBASE, CINAHL, Cochrane, ISI, International Pharmaceutical Abstracts, Scirus, NHS economic, and others, as well as manual search. Inclusion criteria were: prospective studies (assessing all patients before discharge, by a specialized team, at least once a week); with data about ADRs occurring during hospitalization, using WHO's or similar definition of ADR. Two independent reviewers assessed eligibility criteria, extracted data, and evaluated risk of bias.

Results: From 4139 studies initially found, 22 were included. Meta-analysis indicate that ADRs may occur in 16.88% (CI95%: 13.56,20.21%) of patients during hospitalization; however, this estimate has to be viewed with caution because there was significant heterogeneity (I² = 99%). The most significant moderators of heterogeneity were risk of bias, population, ward, and methodology for ADR identification. Low risk of bias studies adjusted for population (pediatric versus adult) had I² = 0%.

Conclusions: These data are useful as a broad characterization of in-hospital ADRs and their frequency. However, due to heterogeneity, our estimates are crude indicators. The wide variation in methodologies was one of the most important moderators of heterogeneity (even among studies using intensive monitoring). We suggest criteria to standardize methodologies and reduce the risk of bias.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adverse Drug Reaction Reporting Systems
  • Databases, Bibliographic
  • Drug-Related Side Effects and Adverse Reactions* / epidemiology*
  • Hospitalization* / statistics & numerical data
  • Humans
  • Incidence
  • Inpatients / statistics & numerical data*
  • Prospective Studies
  • Risk