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Am J Med. 2004 Oct 15;117(8):582-9.

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

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Clinical Trials and Evidence-Based Medicine, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.



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


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.


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.


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.

[Indexed for MEDLINE]

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