Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
PLoS One. 2010 Oct 27;5(10):e13550. doi: 10.1371/journal.pone.0013550.
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.
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 the similarity of the current trial with the previous comparator's trials. In general, no difference was seen in the quality of reporting before and after the release of the CONSORT statement extension 2006 or between the high-impact and low-impact journals.
The conduct and reporting of NI trials can be improved, particularly in terms of maximizing the use of blinding, the use of both ITT and PP analysis, reporting the similarity with the previous comparator's trials to guarantee a valid constancy assumption, and most importantly reporting the method to determine the NI margin.
非劣效性（NI）试验旨在表明新治疗方法的效果不比对照药物差。我们进行了一项综述，以确定 NI 试验的开展和报告方式，以及是否遵循了指南的标准要求。
从 2009 年 2 月 5 日在 PubMed 上随机选择的 300 篇关于 NI 试验的文章中，我们纳入了 227 篇提到 232 项试验的 NI 文章。我们排除了关于生物等效性的研究、健康志愿者的试验、非药物试验以及无法获取全文的文章。很大比例的试验（34.0%）未采用盲法。97.8%的试验报告了 NI 边界，但只有 45.7%的试验报告了确定边界的方法。大多数试验采用意向治疗（ITT）（34.9%）或符合方案（PP）分析（19.4%），而 41.8%的试验同时采用了这两种方法。不到 10%的试验包括安慰剂组，以确认新药和阳性对照药物相对于安慰剂的疗效，不到 5.0%的试验报告了当前试验与之前对照药物试验的相似性。一般来说，在 CONSORT 声明扩展 2006 发布前后，或在高影响力和低影响力期刊之间，NI 试验的报告质量并没有明显差异。
NI 试验的开展和报告可以得到改进，特别是在最大限度地使用盲法、同时采用 ITT 和 PP 分析、报告与之前对照药物试验的相似性以保证有效性假设的有效性，以及最重要的是报告确定 NI 边界的方法方面。
