Ahn C
Division of Clinical Epidemiology, University of Texas Health Science Center at Houston 77030, USA.
Stat Med. 1998 Jul 30;17(14):1537-49. doi: 10.1002/(sici)1097-0258(19980730)17:14<1537::aid-sim872>3.0.co;2-f.
Phase I clinical trials are designed to identify an appropriate dose for experimentation in phase II and III studies. I present the results from a simulation study to evaluate the performance of nine phase I designs involving the standard design, the two-stage modified Storer's design, the two-stage Korn's design, the one-stage modified continual reassessment method (CRM) designs, and the two-stage modified CRM designs. I compare the performance of the above phase I designs in terms of the following criteria: (i) the proportion of the recommended maximum tolerated dose (MTD) at each dose level; (ii) the proportion of patients treated at each dose level; (iii) the average number of patients to complete the trial; (iv) the probability of toxicity observed; and (v) the average number of cohorts to complete the trial. In general, the one-stage modified CRM II and CRM III designs perform well compared with the other designs considered in this study. The one-stage modified CRM II and III designs require much fewer numbers of cohorts than do the two-stage modified CRM II and III designs. The one-stage modified CRM II and III designs avoid the criticisms of the original CRM by reducing the average number of cohorts and toxicity incidences, while estimating the MTD more accurately than does the standard design.
I期临床试验旨在确定适合在II期和III期研究中进行试验的剂量。我展示了一项模拟研究的结果，以评估九种I期设计的性能，这些设计包括标准设计、两阶段改良的斯托勒设计、两阶段科恩设计、单阶段改良的连续重新评估方法（CRM）设计以及两阶段改良的CRM设计。我根据以下标准比较上述I期设计的性能：（i）每个剂量水平下推荐的最大耐受剂量（MTD）的比例；（ii）每个剂量水平下接受治疗的患者比例；（iii）完成试验的患者平均数量；（iv）观察到毒性的概率；以及（v）完成试验的队列平均数量。总体而言，与本研究中考虑的其他设计相比，单阶段改良的CRM II和CRM III设计表现良好。单阶段改良的CRM II和III设计所需的队列数量比两阶段改良的CRM II和III设计少得多。单阶段改良的CRM II和III设计通过减少队列平均数量和毒性发生率避免了对原始CRM的批评，同时比标准设计更准确地估计MTD
