Article Text

Impact of sample size on variation of adverse events and preventable adverse events: systematic review on epidemiology and contributing factors
  1. Constanze Lessing1,
  2. Astrid Schmitz1,
  3. Bernhard Albers2,
  4. Matthias Schrappe1
  1. 1Institute for Patient Safety, University of Bonn, Bonn, Germany
  2. 2German Diabetes Center at the Heinrich-Heine University, Düsseldorf, Germany
  1. Correspondence to Dr Constanze Lessing, Institute for Patient Safety, University of Bonn, D-53111 Bonn, Germany; lessing{at}


Objectives To perform a systematic review of the frequency of (preventable) adverse events (AE/PAE) and to analyse contributing factors, such as sample size, settings, type of events, terminology, methods of collecting data and characteristics of study populations.

Review methods Search of Medline and Embase from 1995 to 2007. Included were original papers with data on the frequency of AE or PAE, explicit definition of study population and information about methods of assessment. Results were included with percentages of patients having one or more AE/PAE. Extracted data enclosed contributing factors. Data were abstracted and analysed by two researchers independently.

Results 156 studies in 152 publications met our inclusion criteria. 144/156 studies reported AE, 55 PAE (43 both). Sample sizes ranged from 60 to 8 493 876 patients (median: 1361 patients). The reported results for AE varied from 0.1% to 65.4%, and for PAE from 0.1% to 33.9%. Variation clearly decreased with increasing sample size. Estimates did not differ according to setting, type of event or terminology. In studies with fewer than 1000 patients, chart review prevailed, whereas surveys with more than 100 000 patients were based mainly on administrative data. No effect of patient characteristics was found.

Conclusions The funnel-shaped distribution of AE and PAE rates with sample size is a probable consequence of variation and can be taken as an indirect indicator of study validity. A contributing factor may be the method of data assessment. Further research is needed to explain the results when analysing data by types of event or terminology.

  • Patient safety
  • adverse event

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Supplementary materials


  • Funding The project ‘patient safety: investigation of the international status quo, assignment on the German healthcare system, and need for action’ was funded by the German ministry of health.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.