Quality of reporting of bioequivalence trials comparing generic to brand name drugs: a methodological systematic review

PLoS One. 2011;6(8):e23611. doi: 10.1371/journal.pone.0023611. Epub 2011 Aug 17.


Background: Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent.

Objective: To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs.

Methodology/principal findings: PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA.

Conclusions/significance: Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Drug Approval / legislation & jurisprudence
  • Drug Approval / organization & administration
  • Drugs, Generic / administration & dosage
  • Drugs, Generic / pharmacokinetics*
  • Europe
  • Humans
  • Pharmaceutical Preparations / administration & dosage
  • Pharmaceutical Preparations / metabolism*
  • Randomized Controlled Trials as Topic
  • Research Report / standards*
  • Therapeutic Equivalency
  • United States
  • United States Food and Drug Administration


  • Drugs, Generic
  • Pharmaceutical Preparations