Xie Xuanqian, Wang Myra, Ng Vivian, Sikich Nancy
Health Quality Ontario, Toronto, ON M5S 1N5, Canada.
Technology Assessment Unit of the McGill University Health Centre, Montréal, QC H4A 3J1, Canada.
J Comp Eff Res. 2018 Sep;7(9):835-843. doi: 10.2217/cer-2018-0035. Epub 2018 Sep 7.
Although published noninferiority trials (NITs) generally conclude that the experimental intervention being studied is noninferior compared with standard therapy or active control, NIT quality is often not satisfactory. We have proposed 14 questions to assist in evaluating the clinical evidence of the experimental versus standard therapy. The aim of these questions is to critically appraise NITs and support proper interpretation of study results. Readers should not only consider whether the confidence interval of the primary effect measure falls within the prespecified noninferiority margin (thus concluding noninferiority), but also assess the similarities between primary and secondary outcomes for the experimental and standard therapy. To conclude noninferiority conceptually is to synthesize evidence from both the current NIT comparing experimental therapy with standard therapy and historical data comparing standard therapy with placebo control. Therefore, readers should use external data sources (e.g., historical data) to validate the study design (e.g., selection of standard therapy, effect measure and the noninferiority margin), and assess the uncertainty of findings due to differences between the observed and expected incidence rates, follow-up time, effects of adjuvant therapy and the secondary outcomes of therapies. Following an explanation of the 14 questions, we then apply the questions to a NIT on intraoperative radiation therapy for early stage breast cancer, as an example.
尽管已发表的非劣效性试验（NITs）通常得出结论，即所研究的实验性干预措施与标准疗法或活性对照相比具有非劣效性，但NIT的质量往往不尽如人意。我们提出了14个问题，以协助评估实验性疗法与标准疗法的临床证据。这些问题的目的是严格评估NITs，并支持对研究结果的正确解读。读者不仅应考虑主要效应指标的置信区间是否落在预先设定的非劣效性界值内（从而得出非劣效性结论），还应评估实验性疗法与标准疗法在主要和次要结局方面的相似性。从概念上来说，得出非劣效性结论就是要综合当前将实验性疗法与标准疗法进行比较的NIT以及将标准疗法与安慰剂对照进行比较的历史数据中的证据。因此，读者应使用外部数据源（如历史数据）来验证研究设计（如标准疗法的选择、效应指标和非劣效性界值），并评估由于观察到的发病率与预期发病率、随访时间、辅助治疗效果以及疗法的次要结局之间的差异而导致的研究结果的不确定性。在对这14个问题进行解释之后，我们随后将这些问题应用于一项关于早期乳腺癌术中放疗的NIT，作为示例。
