Summarising the Evidence for Drug Safety: A Methodological Discussion of Different Meta-Analysis Approaches

Abstract

Evidence on drug safety obtained from randomised clinical trials is very limited due to, among other reasons, their relatively small sample size. Hence, combining the results of available studies can prove particularly useful. This paper reviews the different data sources for summarising drug safety outcomes, according to study design, publication of data, and origin of the information. It then discusses the various types of overviews that can be used in the study of treatment harms, focusing on meta-analyses of aggregate data and meta-analyses of individual patient data, with their advantages and drawbacks, such as publication bias and heterogeneity. Although the different approaches available for combining the results are of great utility in assessing treatment harms, none of them is free from limitations. Therefore, it might be appropriate to perform an analysis of sensitivity to assess whether the results are sensitive to the technique that has been used.