Quality of Reporting of Generic Drug Trials Figure 4. Ratio and 90% confidence intervals for the AUC|0 to infinity 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 FDA 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.g004 We found a high number of articles (55) that did not give the name of the reference drug, so we could not ascertain whether the reference drug was the brand-name or another generic drug. The readers need to know which comparator was used because equivalence trials require the efficacy of the reference treatment to be well established [20,21]. If the reference drug is not the brand- name drug, bio-creep [20] leading to a significant loss of activity compared to the brand-name drug could occur, as was shown in 2 simulation studies [22,23]. The consequences can be important for patients, especially for drugs with an NTI, because small changes in systemic concentration can lead to substantial changes in clinical response and toxicity of the drug. Our results also show lack of transparency in published reports of trials. Important information such as funding source, country where the trial was performed and details about the methodology were frequently missing. Knowing which population was used and how the trial was performed (i.e., randomization method, whether data for some participants were excluded from analysis) is essential to critically judge whether the results are valid and reproducible. More importantly, about one-third of articles of single-dose trials concluding bioequivalence did not report adequately 90% CIs for the 3 criteria required by the FDA. As the EMA required only two of these criteria, also about 20% of these articles did not report these criteria. If the required information to conclude bioequiv- alence is missing, readers cannot judge whether the conclusion is reliable. Our study has some limitations. The search period was short, 2005 to 2008. Nevertheless, our study relied on guidelines published relatively recently by the FDA, in 2003, and by the EMA, in 2001 and updated in 2008. We used PubMed only to identify relevant trials, so our search may not have been exhaustive because of incomplete journal coverage. Embase covers pharma- cology journals well and has indexing terms suited to this topic, so future reviews should also involve searching this database. However, the search strategy we used to obtain articles revealed only 1 additional article in Embase that could have been included in our study. Our sample included few articles of bioequivalence trials performed in Europe or North America. We do not have any satisfactory explanation for this situation. In conclusion, because generic drugs are necessary and are used by many people, we argue for increased transparency of published results of trials comparing generic to brand-name drugs. Efforts PLoS ONE | www.plosone.org 6 August 2011 | Volume 6 | Issue 8 | e23611