room for improvement in conducting and reporting non-inferiority randomized controlled trials on drugs a systematic review在进行改进的余地和报告non-inferiority随机对照试验药物系统回顾.pdfVIP

Room for Improvement in Conducting and Reporting Non-Inferiority Randomized Controlled Trials on Drugs: A Systematic Review 1 1 2 1 1 1,2 Grace Wangge , Olaf H. Klungel , Kit C. B. Roes , Anthonius de Boer , Arno W. Hoes , Mirjam J. Knol * 1 Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Utrecht, The Netherlands, 2 University Medical Center Utrecht, Julius Center for Health Sciences and Primary Care, Utrecht, The Netherlands Abstract Background: A non-inferiority (NI) trial is intended to show that the effect of a new treatment is not worse than the comparator. We conducted a review to identify how NI trials were conducted and reported, and whether the standard requirements from the guidelines were followed. Methodology and Principal Findings: From 300 randomly selected articles on NI trials registered in PubMed at 5 February 2009, we included 227 NI articles that referred to 232 trials. We excluded studies on bioequivalence, trials on healthy volunteers, non-drug trials, and articles of which the full-text version could not be retrieved. A large proportion of trials (34.0%) did not use blinding. The NI margin was reported in 97.8% of the trials, but only 45.7% of the trials reported the method to determine the margin. Most of the trials used either intention to treat (ITT) (34.9%) or per-protocol (PP) analysis (19.4%), while 41.8% of the trials used both methods. Less than 10% of the trials included a placebo arm to confirm the efficacy of the new drug and active comparator against placebo, and less than 5.0% were reporting th