Kocherginsky Masha, Cohen Ezra E W, Karrison Theodore
Department of Health Studies, University of Chicago, Chicago, Illinois 60637, USA.
J Biopharm Stat. 2009;19(3):524-9. doi: 10.1080/10543400902802441.
For experimental anticancer agents that may have both cytostatic and cytotoxic effects, assessment of response rates alone may not capture the full impact of the treatment. Oncologists are therefore interested in assessing both response and stable disease rates in early phase clinical trials of such therapies. We describe the design of a single-arm, Phase II clinical trial for the simultaneous evaluation of objective response and stable disease (lack of early tumor progression) rates using standard RECIST criteria. Demonstration of a sufficiently high rate for either of these endpoints will lead to rejection of the null hypothesis and a conclusion that the treatment warrants further study. A design is chosen that satisfies the desired type I error constraint and has sufficient statistical power at several selected points within the alternative hypothesis space using a restricted search algorithm. An early stopping rule for lack of efficacy is incorporated. The method is illustrated by the design of a Phase II clinical trial in head and neck cancer.
对于可能兼具细胞生长抑制和细胞毒性作用的实验性抗癌药物，仅评估缓解率可能无法全面反映治疗效果。因此，肿瘤学家有兴趣在这类疗法的早期临床试验中同时评估缓解率和疾病稳定率。我们描述了一项单臂II期临床试验的设计，该试验使用标准的RECIST标准同时评估客观缓解率和疾病稳定（无早期肿瘤进展）率。这两个终点中任何一个显示出足够高的发生率都将导致零假设被拒绝，并得出该治疗值得进一步研究的结论。选择一种设计，使其满足所需的I型错误约束，并使用受限搜索算法在备择假设空间内的几个选定关键点上具有足够的统计效力。纳入了因缺乏疗效而提前终止试验的规则。通过头颈癌II期临床试验的设计来说明该方法。
