Jin Hua
School of Mathematical Sciences, South China Normal University, Guangzhou 510631, China.
Contemp Clin Trials. 2007 Jul;28(4):525-31. doi: 10.1016/j.cct.2007.03.003. Epub 2007 Mar 14.
Phase II clinical trials in oncology are used to initially evaluate the therapeutic efficacy of a new treatment regimen. Simon's two-stage design is commonly used for such trials. However, he only focused on the "response rate", the proportion of patients experiencing tumor regression. In clinical practice, it is preferred of a sequential design to monitor antitumor activity as well as toxicity. Conaway and Petroni proposed a method for designing phase II trials on the basis of both treatment efficacy and safety, which imply an equal weighing of response and toxicity. In this paper, we developed an alternative test to cope with the trade-off between safety and efficacy. The main idea is to control for the marginal type I errors of response rate and toxicity rate separately. We provide guides on searching the stopping and rejecting regions and determination of sample size. The proposed method has advantage over other designs, including those of Conaway and Petroni's and Bryant and Day's, that it can definitely control one type I error of the interests such as treatment antitumor activity or safety and is robust against the real association parameter. Furthermore, it is conceptive intuitive, very simple to implement, and also feasible for the requirement of small sample size in a phase II trial.
肿瘤学中的II期临床试验用于初步评估新治疗方案的疗效。西蒙两阶段设计常用于此类试验。然而，他只关注“缓解率”，即经历肿瘤消退的患者比例。在临床实践中，采用序贯设计来监测抗肿瘤活性和毒性更为可取。康纳韦和彼得罗尼提出了一种基于治疗效果和安全性设计II期试验的方法，这意味着对缓解和毒性进行同等权衡。在本文中，我们开发了一种替代检验方法来应对安全性和有效性之间的权衡。主要思想是分别控制缓解率和毒性率的边际I类错误。我们提供了搜索停止和拒绝区域以及确定样本量的指南。所提出的方法优于其他设计，包括康纳韦和彼得罗尼的设计以及布莱恩特和戴的设计，它可以明确控制诸如治疗抗肿瘤活性或安全性等感兴趣的一种I类错误，并且对真实关联参数具有稳健性。此外，它概念直观，实施非常简单，对于II期试验中小样本量的要求也可行。
