Dendrix Research, Sao Paulo, Brazil.
Acta Oncol. 2012 Sep;51(7):890-6. doi: 10.3109/0284186X.2012.702924.
Determining the non-inferiority margin is an essential step in the design and interpretation of non-inferiority trials, and this margin should be preferably justified on clinical and statistical grounds.
After a PubMed search for phase III trials in advanced breast cancer (BC) or non-small cell lung cancer (NSCLC) published between January 1998 and December 2009 in 11 leading journals, non-inferiority trials were selected by manual search of the full papers.
Twenty-four of 195 trials had a primary non-inferiority hypothesis. When the two six-year study periods were compared, there were time trends within BC and NSCLC, with most non-inferiority trials in BC reported in the first six-year period, and vice-versa for NSCLC. The median sample size was larger for non-inferiority than superiority trials (p < 0.01). The choice of a non-inferiority margin was reportedly justified in only five cases. Non-inferiority trials were more likely than superiority trials to yield positive results (p < 0.001), as were trials in breast cancer (p = 0.02).
Non-inferiority margins for cancer trials appear to be chosen mostly on historical grounds. Since nearly three-quarters of non-inferiority trials achieve their primary objective, the extent to which the choice of margins has influence on trial results remains to be determined.
确定非劣效性边界是设计和解释非劣效性试验的重要步骤，并且最好基于临床和统计学依据来证明该边界的合理性。
在对 11 种主要期刊上发表的 1998 年 1 月至 2009 年 12 月期间的三期乳腺癌（BC）或非小细胞肺癌（NSCLC）的文献进行 PubMed 检索后，通过对全文的手动搜索，选择非劣效性试验。
在 195 项试验中，有 24 项具有主要的非劣效性假设。当比较这两个六年研究期时，BC 和 NSCLC 中都存在时间趋势，大多数 BC 的非劣效性试验在前六年报告，而 NSCLC 则相反。非劣效性试验的样本量中位数大于优效性试验（p < 0.01）。仅在 5 例中报告了非劣效性边界的选择是合理的。非劣效性试验比优效性试验更有可能产生阳性结果（p < 0.001），乳腺癌试验也是如此（p = 0.02）。
癌症试验的非劣效性边界似乎主要是基于历史依据选择的。由于近四分之三的非劣效性试验达到了主要目标，因此边界选择对试验结果的影响程度仍有待确定。
