Quality of Reporting of Generic Drug Trials Figure 3. Ratio and 90% confidence intervals for the AUC|0 to t 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 the US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) for confidence intervals of the ratio are within 80% and 125% of the ratio for the generic to brand-name drug. doi:10.1371/journal.pone.0023611.g003 the basis of pharmacokinetic criteria: rate of absorption as determined by the peak plasma concentration (Cmax), area under the plasma concentration–time curve from time 0 to time t = end of the study (AUC|0 to t) and to infinity (AUC|0 to infinity). Limits used to conclude bioequivalence are fixed by regulatory agencies. Noninferiority and equivalence trials aim to demonstrate that the experimental treatment is not clinically different from the comparator (an active control treatment) by more than a pre- specified small amount known as the equivalence margin and which is fixed by the investigators of the trial and varies greatly among trials. Equivalence trials are usually parallel-group trials including a large number of patients (the smaller the margin, the larger the number of patients) and clinical outcomes. Some previous methodological reviews [16,17] assessed the quality of reporting for noninferiority and/or equivalence trials and showed important deficiencies, but to our knowledge, this is the first review focusing on bioequivalence trials. Substituting brand-name for generic for drugs is crucial for reducing healthcare costs. As an example, in the United States, the use of generic drugs has saved the healthcare system more than $734 billion between 1999 and 2008, with approximately $121 billion in savings in 2008 alone. So, the development of generic drugs is important. Because this development leads to the use of generics by millions of patients, the evaluation of these drugs must be highly transparent, with registration of trials, publication of results of registered trials and adequate reporting of results. Our aim was not to discuss the methodology of trials assessing generic drugs but to determine whether the variables currently recom- mended to conclude bioequivalence were adequately reported. Only one article reported a trial’s registration number in an international database. Given the number of existing generic drugs, it is likely that bioequivalence data are not published for most of them. During the study period, 1,661 new generic drugs were approved by the FDA [18]. Reports of trials assessing generic drugs were not available on FDA or EMA websites. Moreover, our sample of published reports of bioequivalence trials included mostly positive bioequivalence trial results. So publication bias [19] may also affect bioequivalence trials comparing generic to brand-name drugs because it is not likely that only 10% of trials failed to demonstrate bioequivalence. PLoS ONE | www.plosone.org 5 August 2011 | Volume 6 | Issue 8 | e23611