非劣效性(NI)试验越来越受欢迎。当新治疗维持标准治疗的大部分治疗效果时,建立新治疗与标准治疗相比的NI。还需要有效的NI试验来显示测定灵敏度,证明标准治疗具有预期效果,其大小与先前安慰剂对照研究中报道的相当。三臂NI试验是一项临床研究,包括一种新的治疗方法,标准治疗和安慰剂。为三臂NI试验开发的大多数统计方法都是为仅存在一种新疗法而设计的。最近,我们开发了一个单步程序,用于处理采用多种新疗法的NI试验,其总体家族错误率控制在特定水平.在这篇文章中,我们将单步程序扩展到两种新的NI试验的增加程序和多种新疗法.对测试功率的比较研究表明,与单步过程相比,两种提出的升压过程都提供了显着的功率改善。提出的两种升级程序之一还允许在敏感性假设和NI假设之间分配不同错误率的灵活性,以便在设计NI试验时将更少的患者分配给安慰剂成为可能。我们使用来自临床试验的数据来说明新程序。
Non-inferiority (NI) trials are becoming more popular. The NI of a new treatment compared with a standard treatment is established when the new treatment maintains a substantial fraction of the treatment effect of the standard treatment. A valid NI trial is also required to show assay sensitivity, the demonstration of the standard treatment having the expected effect with a size comparable to those reported in previous placebo-controlled studies. A three-arm NI trial is a clinical study that includes a new treatment, a standard treatment and a placebo. Most of the statistical methods developed for three-arm NI trials are designed for the existence of only one new treatment. Recently, a single-step procedure was developed to deal with NI trials with multiple new treatments with the overall familywise error rate controlled at a specified level. In this article, we extend the single-step procedure to two new step-up procedures for NI trials with multiple new treatments. A comparative study of test power shows that both proposed step-up procedures provide a significant improvement of power when compared to the single-step procedure. One of the two proposed step-up procedures also allows the flexibility of allocating different error rates between the sensitivity hypothesis and the NI hypotheses so that the assignment of fewer patients to the placebo becomes possible when designing NI trials. We illustrate the new procedures using data from a clinical trial.