In the development of cancer treatment vaccines, phase II clinical studies are conducted to examine the efficacy of a vaccine in order to screen out vaccines with minimal activity. Immune responses are commonly used as the primary endpoint for assessing vaccine efficacy. With respect to study design, Simon's two-stage design is a popular format for phase II cancer clinical studies because of its simplicity and ethical considerations. Nonetheless, it is not straightforward to apply Simon's two-stage design to cancer vaccine studies when performing immune assays in batches, as outcomes from multiple patients may be correlated with each other in the presence of batch effects. This violates the independence assumption of Simon's two-stage design. In this paper, we numerically explore the impact of batch effects on Simon's two-stage design, propose a batch-effect adjusted Simon's two-stage design, demonstrate the proposed design by both a simulation study and a therapeutic human papillomavirus vaccine trial, and briefly introduce a software that implements the proposed design.

中文翻译：

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批量效应调整西蒙癌症疫苗临床研究的两阶段设计

在癌症治疗疫苗的开发过程中，进行了 II 期临床研究以检查疫苗的功效，以筛选出活性最低的疫苗。免疫反应通常用作评估疫苗效力的主要终点。在研究设计方面，Simon 的两阶段设计因其简单性和伦理考虑而成为 II 期癌症临床研究的流行形式。尽管如此，在批量进行免疫测定时，将 Simon 的两阶段设计应用于癌症疫苗研究并不简单，因为在存在批量效应的情况下，多个患者的结果可能相互关联。这违反了西蒙两阶段设计的独立性假设。在本文中，我们数值探讨了批次效应对西蒙的影响