Julius Center for Health Sciences and Primary Care, Utrecht University Medical Center, Utrecht, The Netherlands.
BMC Med Res Methodol. 2013 May 30;13:70. doi: 10.1186/1471-2288-13-70.
Non-inferiority (NI) trials in drug research are used to demonstrate that a new treatment is not less effective than an active comparator. Since phase IV trials typically aim at informing a clinical decision, the value of a phase IV non-inferiority trial hinges also on its clinical relevance. In such trials, clinical relevance would refer to the added benefit claims of a specific drug, apart from efficacy, relative to its comparator drug in the trial.
In this study, we reviewed 41 phase IV trials and extracted information on whether the authors mentioned any additional benefit beyond the NI (efficacy) claim of the drug and whether the additional benefit was proven in the trial. We checked whether the additional claim was based on descriptions only or on formal statistical analyses.
Our results showed that 22 out of the 41 NI trials mentioned additional benefit of the test drug and most of these claims were related to the safety profile. Of all the post-authorization NI trials that claimed additional benefit, 10 out of 22 NI trials used formal statistical analyses to show additional benefit, and only one included a sample size calculation for the additional benefit prior to the trial.
We conclude that there is room for improvement in terms of designing phase IV NI trials with added benefit claims and in proving these additional claims.
药物研究中的非劣效性（NI）试验用于证明新的治疗方法不比活性对照药物差。由于 IV 期试验通常旨在为临床决策提供信息，因此 IV 期非劣效性试验的价值还取决于其临床相关性。在这类试验中，临床相关性是指特定药物相对于试验中的对照药物在疗效之外的额外获益主张。
本研究回顾了 41 项 IV 期试验，并提取了关于作者是否提到药物的非劣效性（疗效）主张之外的任何额外获益，以及试验是否证明了额外获益的信息。我们检查了额外获益主张是否仅基于描述或基于正式的统计分析。
我们的结果表明，41 项 NI 试验中有 22 项提到了试验药物的额外获益，其中大多数与安全性特征有关。在所有声称具有额外获益的上市后 NI 试验中，22 项 NI 试验中有 10 项使用了正式的统计分析来显示额外获益，仅有一项在试验前对额外获益进行了样本量计算。
我们的结论是，在设计具有额外获益主张的 IV 期 NI 试验和证明这些额外获益主张方面，还有改进的空间。
