OBJECTIVES: Several recommendations are available to conduct and report a systematic review on drug’s safety. This study is aimed at identifying and comparing the methodology of the two most used recommendations to conduct and report systematic reviews on drug’s safety.

METHODS: Two systematic reviews were conducted following the recommendations “Cochrane Handbook for Systematic Reviews of Interventions” and “Systematic Reviews’ Centre for Reviews and Dissemination guidance for undertaking reviews in healthcare”. The methods of each recommendation where characterised and the results and the discussion of each systematic review were also evaluated.

RESULTS: The methodology of both recommendations is similar. The review question was structured. Both recommendations suggest to include pre- and post-marketing data. The recommended data sources differed and, consequently, the results of the systematic reviews (37 vs. 35 studies). Other aspects of search literature were identical. Different tools are suggested to evaluate the methodological quality of the included studies. For case reports, both recommendations only report some questions that may be helpful to assess risk of bias. The reporting of the results and discussion is also identical for both recommendations.

CONCLUSIONS: Few methodological differences were observed between the recommendations to conduct a systematic review on drug’s safety. Combining their methods into a single and recognised recommendation could be of great value.