Design issues of randomized phase II trials and a proposal for phase II screening trials
Design issues of randomized phase II trials and a proposal for phase II screening trials
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DOI：
10.1200/jco.2005.01.149
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发表时间：
2005-10-01
影响因子：
45.3
通讯作者：
Smith, MA
中科院分区：
文献类型：
--
作者：
Rubinstein, LV;Korn, EL;Smith, MA
改善癌症治疗的未来进展可以通过更好地优先考虑III期评估的新治疗来加速。从历史上看，第二阶段试验一直是确定优先次序过程中的关键组成部分。长期以来，人们一直有兴趣使用II期试验，随机对照标准治疗对照组或额外的实验组，以提供比与历史对照相比更大的保证，即新药物或方案是有前途的，需要进一步评价。已开发和使用的相关试验设计包括II期选择设计、随机II期设计（包括参考标准治疗对照组）和II/III期设计。我们提出了我们自己的探索发展的可能性“第二阶段筛选试验”，其中初步和非确定性的随机比较实验方案的标准治疗（最好使用中间终点）通过仔细调整假阳性错误率（α或I型错误）和假阴性错误率（β或II型错误），以便在样本量仍然有限的情况下，靶向治疗获益可能是适当的。如果可以保护进行确定性III期试验的能力，并且如果研究者认为通过明智地选择假阳性概率和假阴性概率以及靶向治疗效果的大小，他们可以适当地平衡筛选无用方案与可靠地检测有用方案的冲突要求，则II期筛选试验设计可能适合应用。
Future progress in improving cancer therapy can be expedited by better prioritization of new treatments for phase III evaluation. Historically, phase II trials have been key components in the prioritization process. There has been a long-standing interest in using phase II trials with randomization against a standard-treatment control arm or an additional experimental arm to provide greater assurance than afforded by comparison to historic controls that the new agent or regimen is promising and warrants further evaluation. Relevant trial designs that have been developed and utilized include phase II selection designs, randomized phase II designs that include a reference standard-treatment control arm, and phase II/III designs. We present our own explorations into the possibilities of developing "phase II screening trials," in which preliminary and nondefinitive randomized comparisons of experimental regimens to standard treatments are made (preferably using an intermediate end point) by carefully adjusting the false-positive error rates (alpha or type I error) and false-negative error rates (beta or type II error), so that the targeted treatment benefit may be appropriate while the sample size remains restricted. If the ability to conduct a definitive phase III trial can be protected, and if investigators feel that by judicious choice of false-positive probability and false-negative probability and magnitude of targeted treatment effect they can appropriately balance the conflicting demands of screening out useless regimens versus reliably detecting useful ones, the phase II screening trial design may be appropriate to apply.