Availability of large-scale evidence on specific harms from systematic reviews of randomized trials

Am J Med. 2004 Oct 15;117(8):582-9. doi: 10.1016/j.amjmed.2004.04.026.


Purpose: To assess how frequently systematic reviews of randomized controlled trials convey large-scale evidence on specific, well-defined adverse events.

Methods: We searched the Cochrane Database of Systematic Reviews for reviews containing quantitative data on specific, well-defined harms for at least 4000 randomized subjects, the minimum sample required for adequate power to detect an adverse event due to an intervention in 1% of subjects. Main outcome measures included the number of reviews with eligible large-scale data on adverse events, the number of ineligible reviews, and the magnitude of recorded harms (absolute risk, relative risk) based on large-scale evidence.

Results: Of 1727 reviews, 138 included evidence on > or =4000 subjects. Only 25 (18%) had eligible data on adverse events, while 77 had no harms data, and 36 had data on harms that were nonspecific or pertained to <4000 subjects. Of 66 specific adverse events for which there were adequate data in the 25 eligible reviews, 25 showed statistically significant differences between comparison arms; most pertained to serious or severe adverse events and absolute risk differences <4%. In 29% (9/31) of a sample of large trials in reviews with poor reporting of harms, specific harms were presented adequately in the trial reports but were not included in the systematic reviews.

Conclusion: Systematic reviews can convey useful large-scale information on adverse events. Acknowledging the importance and difficulties of studying harms, reporting of adverse effects must be improved in both randomized trials and systematic reviews.

Publication types

  • Review

MeSH terms

  • Humans
  • Meta-Analysis as Topic
  • Randomized Controlled Trials as Topic / adverse effects*
  • Randomized Controlled Trials as Topic / methods
  • Sample Size