Intended for healthcare professionals

Research Methods & Reporting

How to use FDA drug approval documents for evidence syntheses

BMJ 2018; 362 doi: (Published 10 July 2018) Cite this as: BMJ 2018;362:k2815
  1. Aviv Ladanie, research fellow1 2,
  2. Hannah Ewald, research fellow1 2 3,
  3. Benjamin Kasenda, senior scientist1 4,
  4. Lars G Hemkens, senior scientist1
  1. 1Basel Institute for Clinical Epidemiology and Biostatistics, Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland
  2. 2Swiss Tropical and Public Health Institute (Swiss TPH), Basel, Switzerland
  3. 3University Medical Library, University of Basel, Basel, Switzerland
  4. 4Departments of Medical Oncology and of Haematology, University Hospital Basel and University of Basel, Basel, Switzerland
  1. Correspondence to: L G Hemkens lars.hemkens{at}
  • Accepted 18 May 2018

Evidence syntheses may benefit from using aggregated clinical trial information in approval documents published online by the US Food and Drug Administration (FDA). We provide practical guidance on how to access and use this source of information for evidence syntheses on treatment effects of drugs and therapeutic biologics.

Summary box

  • There is compelling evidence that published trial information is selectively reported and that results not showing favourable effects of the tested treatments often remain unpublished

  • Clinical trial information published by regulatory authorities such as the US Food and Drug Administration (FDA) may help to reduce such reporting biases

  • FDA approval documents are long and do not follow the typical structure of medical journal articles, which may discourage reviewers from using them for evidence syntheses

  • Our practical guidance on how to efficiently identify and use approval documents to find the relevant information may help promoting the use of this valuable data source for evidence syntheses

Publicly accessible approval documents published by the US Food and Drug Administration (FDA) provide important insights into reporting biases in articles published in peer reviewed medical journals,1234 but the FDA data can also be used to directly minimise the impact of such biases on the results and conclusions in evidence syntheses,5 obtain information not disclosed in published clinical trials reports,6 and identify unpublished clinical trials to increase precision of effect estimates.7

For example, almost 20 years ago, Man-Son-Hing and colleagues5 showed that incorporating unpublished trials into a meta-analysis on quinine for nocturnal leg cramps substantially reduced the estimated efficacy. The bias occurred because almost all published trials had larger effects than the unpublished studies. Similarly, Turner and colleagues found that 22 (31%) of 71 trials discussed in FDA approval documents of 12 antidepressants were not published, and that publication was …

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