Sequential designs for phase I clinical trials with late-onset toxicities
Sequential designs for phase I clinical trials with late-onset toxicities
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DOI：
10.1111/j.0006-341x.2000.01177.x
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发表时间：
2000-12-01
期刊：
影响因子：
1.9
通讯作者：
Chappell, R
中科院分区：
文献类型：
--
作者：
Cheung, YK;Chappell, R
I期临床试验的传统设计要求在分配下一个患者或组之前对每个患者（或一小组患者）进行完全随访。在评估辐射的迟发效应或化学预防剂的毒性等情况下，这可能导致试验持续时间过长。我们提出了一种新的方法，称为时间到事件的持续重新评估方法（TITE-CRM），允许患者以交错的方式进入。它是连续再评估方法的扩展（CRM; O 'Quigley，Pepe和Fisher，1990，Biometrics 46，33-48）。我们还注意到，这种时间毒性的方法可以应用于扩展其他设计的短期毒性研究。我们证明了推荐剂量的TITE-CRM收敛到正确的水平在一定条件下。一项模拟研究表明，我们的方法的准确性和安全性与CRM的，而前者需要更短的试验时间：一个试验，将需要长达12年的CRM完成，可以减少到2-4年，我们的方法。
Traditional designs for phase I clinical trials require each patient (or small group of patients) to be completely followed before the next patient or group is assigned. In situations such as when evaluating late-onset effects of radiation or toxicities from chemopreventive agents, this may result in trials of impractically long duration. We propose a new method, called the time-to-event continual reassessment method (TITE-CRM), that allows patients to be entered in a staggered fashion. It is an extension of the continual reassessment method (CRM; O'Quigley, Pepe, and Fisher, 1990, Biometrics 46, 33-48). We also note that this time-to-toxicity approach can be applied to extend other designs for studies of short-term toxicities. We prove that the recommended dose given by the TITE-CRM converges to the correct level under certain conditions. A simulation study shows our method's accuracy and safety are comparable with CRM's while the former takes a much shorter trial duration: a trial that would take up to 12 years to complete by the CRM could be reduced to 2-4 years by our method.