Reducing sample sizes in two stage phase II cancer trials by using continuous tumour shrinkage end-points
Reducing sample sizes in two stage phase II cancer trials by using continuous tumour shrinkage end-points
复制标题
DOI：
10.1016/j.ejca.2010.12.007
复制
发表时间：
2011-05-01
影响因子：
8.4
通讯作者：
Eisen, Tim G.
中科院分区：
文献类型：
--
作者：
Wason, James M. S.;Mander, Adrian P.;Eisen, Tim G.
减少临床试验所需的患者数量对于缩短开发时间非常重要。II期癌症试验通过由总病变直径的百分比变化形成的二元终点来评估一种新化合物的肿瘤缩小效果。我们比较了使用二进制终点的单臂两阶段设计和直接使用连续终点的单臂两阶段设计。使用连续终点会导致较低的期望和最大样本量。对于更大规模的试验，降幅约为37%。这假设选择连续终点的二分点以给出最佳样本大小，否则使用二进制终点的试验设计表现得更差。我们考虑了之前一个使用Simon两阶段设计的试验，结果表明，如果使用连续终点，试验的预期样本量和最大样本量将减少约50%。在两阶段癌症试验中使用连续终点会导致大量样本量的减少。本文讨论的方法在完全应答数低的情况下效果最好，在几种类型的癌症中也是如此。我们讨论了如果情况不是这样，可以做些什么。(C)2010爱思唯尔有限公司。保留所有权利。
Reducing the number of patients required for a clinical trial is important for shortening development time. Phase II cancer trials assess the tumour-shrinking effect of a novel compound through a binary end-point formed from the percentage change in total lesion diameter. We compare single-arm two-stage designs which use the binary end-point to those which directly use the continuous end-point.Using the continuous end-point results in lower expected and maximum sample sizes. For larger trials the reduction is around 37%. This assumes that the dichotomisation point of the continuous end-point is chosen to give the best sample size, with the trial design using the binary end-point performing even worse otherwise. We consider a previous trial designed using a Simon two-stage design and show that if the continuous end-point had been used, the expected and maximum sample sizes of the trial would be reduced by around 50%.Using the continuous end-point in a two-stage cancer trial results in large sample size reductions. The methods discussed in this paper work best when the number of complete responses is low, as is true in several types of cancer. We discuss what could be done if this is not the case. (C) 2010 Elsevier Ltd. All rights reserved.