A comparison of three different sources of data in assessing the frequencies of adverse reactions to amiodarone

Br J Clin Pharmacol. 2004 May;57(5):616-21. doi: 10.1111/j.0306-5251.2003.02055.x.


Aims: To compare the frequencies of adverse drug reactions (ADRs) to amiodarone from three separate datasets: (i) a meta-analysis of clinical trials, (ii) spontaneous reports published in medical journals, and (iii) spontaneous reports sent to the World Health Organization (WHO).

Methods: We classified the ADRs into eight categories, based on the site involved, and built a rank order of the ADRs by category (from most to least commonly reported) for each dataset. We also calculated the relative proportions for all eight ADR categories within each dataset, in order to be able to compare the distributions of ADR frequencies: we assigned an index value of 1.0 to the frequency of respiratory toxicity in each set and calculated values for the other ADRs relative to respiratory toxicity.

Results: Thyroid disorders were the most commonly reported ADRs in the WHO dataset. In contrast, published case reports showed a preponderance of respiratory disorders, while in the meta-analysis cardiac conduction problems were the most frequent. The rank orders of ADRs differed among the three datasets, as did the index values of specific ADR categories with respect to the respiratory category.

Conclusions: The distributions of ADR rank order and relative frequencies are dissimilar among the three datasets, as each dataset compiles information in a different way. Nevertheless, each dataset has its own specific strengths, and all three should be used together in obtaining a complete picture of a drug's safety profile. Important therapeutic and regulatory decisions should not simply be based on one source of data.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Amiodarone / adverse effects*
  • Data Collection / methods*
  • Data Collection / statistics & numerical data
  • Humans
  • Meta-Analysis as Topic
  • Periodicals as Topic / statistics & numerical data
  • Randomized Controlled Trials as Topic / statistics & numerical data
  • World Health Organization


  • Amiodarone