in 86% of articles and were mainly concomitant medication use (57%), significant psychiatric or medical disease (56%) and positivity for hepatitis B or C virus (50%) and HIV (40%). Results and conclusions for single-dose bioequivalence trials (Table S4) Among the reports of single-dose trials (n = 73), for 65 (89%) the conclusion was bioequivalence, for 7 (10%) non-bioequivalence, and for one, the conclusion was unclear. For the articles with bioequivalence conclusion, 45 (69%) reported 90% CIs within the limits required for the 3 criteria as required by the FDA, 15 (23%) reported appropriate 90% CIs for 2 criteria, 8 of which reported both Cmax and AUC|0 to t as required by the EMA, and 2 (2%) did not report any 90% CIs for the criteria. Two articles (3%) with bioequivalence conclusions described 90% CIs outside the limits. In one trial, the 90% CI for Cmax for the ratio was between 77% and 133%, which is authorized by EMA for highly variable drugs (i.e., drugs exhibiting intra-subject variability greater than 30%). Figures 2, 3 and 4 show the details of the 90% CIs for the ratio of generic to brand-name for Cmax, AUC|0 to t and, AUC|0 to infinity of Quality of Reporting of Generic Drug Trials generic to brand-name drugs for all reports of single-dose trials with bioequivalence conclusions separately for NTI and non-NTI drugs. Discussion Generic drugs are used by many patients for economic reasons, so their evaluation must be highly transparent. We systematically reviewed the quality of reporting of bioequivalence trials comparing generic to brand-name drugs and found it to be overall poor. In 41% of articles, the name of the reference drug was not given. Information was insufficient for funding source, important items for assessing the risk of bias within trials and country where the trial was performed. More importantly, a substantial number of articles of single-dose trials concluding bioequivalence did not report the 90% CI for the criteria required by the Health authorities. The objectives and methodology of bioequivalence trials differ greatly from those of noninferiority and equivalence trials. Bioequivalence trials are usually randomized crossover trials including a small sample of healthy volunteers aiming to demonstrate that 2 molecules are chemically bioequivalent on Figure 2. Ratio and 90% confidence intervals for the Cmax of single-dose bioequivalence trials with a conclusion of bioequivalence. Black squares indicate ratio; horizontal lines, 90% CI. The size of each square reflects the number of participants enrolled. Limits of acceptance required by both FDA and EMA for confidence intervals of the ratio are within 80% and 125% of the ratio of the generic to brand-name drug. doi:10.1371/journal.pone.0023611.g002 PLoS ONE | www.plosone.org 4 August 2011 | Volume 6 | Issue 8 | e23611