Medical and Pharmaceutical Statistics Research Unit, Lancaster University, Lancaster, UK.
Stat Med. 2013 Jul 10;32(15):2544-54. doi: 10.1002/sim.5716. Epub 2012 Dec 19.
In phase III cancer clinical trials, overall survival is commonly used as the definitive endpoint. In phase II clinical trials, however, more immediate endpoints such as incidence of complete or partial response within 1 or 2 months or progression-free survival (PFS) are generally used. Because of the limited ability to detect change in overall survival with response, the inherent variability of PFS and the long wait for progression to be observed, more informative and immediate alternatives to overall survival are desirable in exploratory phase II trials. In this paper, we show how comparative trials can be designed and analysed using change in tumour size as the primary endpoint. The test developed is based on the framework of score statistics and will formally incorporate the information of whether patients survive until the time at which change in tumour size is assessed. Using an example in non-small cell lung cancer, we show that the sample size requirements for a trial based on change in tumour size are favourable compared with alternative randomized trials and demonstrate that these conclusions are robust to our assumptions.
在 III 期癌症临床试验中，总生存期通常被用作最终终点。然而，在 II 期临床试验中，更直接的终点，如 1 或 2 个月内完全或部分缓解的发生率或无进展生存期（PFS），通常被使用。由于反应对总生存期变化的检测能力有限，PFS 的固有变异性以及对进展进行观察的长时间等待，因此在探索性 II 期试验中，需要更具信息量和更直接的替代方案。在本文中，我们展示了如何使用肿瘤大小变化作为主要终点来设计和分析对照试验。所开发的检验基于评分统计的框架，并将正式纳入患者是否存活到评估肿瘤大小变化时间的信息。我们使用非小细胞肺癌的一个例子表明，基于肿瘤大小变化的试验所需的样本量与其他随机试验相比是有利的，并证明这些结论对我们的假设具有稳健性。
