Conventional seamless phase 2/3 design with fixed sample size determination (SSD) has gained its popularity in oncology drug development due to attractive features such as significantly shortening the development timeline, minimizing sample size, as well as early decision making. However, this design is not immune to inaccurate treatment effect assumption when only limited efficacy data are available at study design stage. We propose an innovative seamless phase 2/3 study design with flexible SSD for oncology trials, in which the trial is designed under a distribution of treatment effect instead of one single assumption due to huge uncertainty of treatment effect at design stage and the sample size for end of phase 3 analysis is not predetermined at design stage, but rather dynamically determined based on observed treatment effect at phase 2 portion. Some practical sample size determination rules for end of phase 3 analysis will be discussed. The proposed design can lead to reduced sample size or/and improved power compared with conventional seamless phase 2/3 design with fixed SSD. This innovative study design can be especially useful for programs with aggressive development strategy to expedite the process in delivering efficacious treatment to patients.

中文翻译：

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具有灵活样本量确定的无缝 2/3 期肿瘤学试验设计。

具有固定样本量测定 (SSD) 的传统无缝 2/3 期设计由于显着缩短开发时间、最小化样本量以及早期决策等吸引人的特性而在肿瘤药物开发中广受欢迎。然而，当在研究设计阶段只有有限的疗效数据可用时，这种设计不能避免不准确的治疗效果假设。我们提出了一种创新的无缝 2/3 期研究设计，采用灵活的 SSD 进行肿瘤学试验，由于设计阶段治疗效果的巨大不确定性和样本量的样本量，该试验是在治疗效果分布而不是单一假设下设计的。第 3 阶段分析的结束未在设计阶段预先确定，而是根据在第 2 阶段部分观察到的治疗效果动态确定的。将讨论用于第 3 阶段分析结束的一些实际样本量确定规则。与具有固定 SSD 的传统无缝阶段 2/3 设计相比，所提出的设计可以减少样本大小或/和提高功率。这种创新的研究设计对于具有积极发展战略的项目特别有用，可以加快为患者提供有效治疗的过程。