Harms are assessed inconsistently and reported inadequately part 1: systematic adverse events

J Clin Epidemiol. 2019 Sep;113:20-27. doi: 10.1016/j.jclinepi.2019.04.022. Epub 2019 May 2.


Objectives: We examined systematic adverse events (AEs) in Part 1 (of 2) of a study describing the assessment and reporting of AEs in clinical trials.

Study design and setting: We examined 52 public and nonpublic data sources about trials of quetiapine for bipolar depression using data from the Multiple Data Sources study. We extracted and compared information about systematic AEs (i.e., AEs assessed for all participants) in six prespecified domains: cardiovascular, cholesterol, endocrine, extrapyramidal symptoms, mania, and weight.

Results: Eligible trials did not assess and report the same systematic AEs, and most results were not available in public sources. Overall, public sources reported 159 results, of which 92 of 159 (58%) included sufficient statistical information to calculate the treatment effect and its precision. Nonpublic sources reported 636 results; 630 of 636 (99%) reported sufficient statistical information.

Conclusion: Systematic AEs were defined and analyzed in many ways, which led to many numerical results. Most systematic AEs were not mentioned in public sources. To minimize bias, methods for defining and analyzing potential AEs should be prespecified in trial registers and protocols. All trial results should be publicly available so that stakeholders can compare benefits and AEs. Trials could report core sets of AEs to facilitate decision-making.

Keywords: Adverse events; Clinical trials; Drug safety; Harms; Open science; Reporting bias.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Bipolar Disorder / drug therapy*
  • Data Accuracy
  • Drug-Related Side Effects and Adverse Reactions
  • Gabapentin / adverse effects*
  • Gabapentin / therapeutic use*
  • Humans
  • Neuralgia / drug therapy*
  • Quetiapine Fumarate / adverse effects*
  • Quetiapine Fumarate / therapeutic use*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Research Report


  • Quetiapine Fumarate
  • Gabapentin