Rubinstein Lawrence V, Korn Edward L, Freidlin Boris, Hunsberger Sally, Ivy S Percy, Smith Malcolm A
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
J Clin Oncol. 2005 Oct 1;23(28):7199-206. doi: 10.1200/JCO.2005.01.149.
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.
通过更好地确定新疗法进行III期评估的优先级，可以加快癌症治疗方面的未来进展。从历史上看，II期试验一直是确定优先级过程中的关键组成部分。长期以来，人们一直关注使用与标准治疗对照臂或额外实验臂进行随机分组的II期试验，以比与历史对照相比更能确保新药物或方案有前景并值得进一步评估。已开发和使用的相关试验设计包括II期筛选设计、包含参考标准治疗对照臂的随机II期设计以及II期/III期设计。我们展示了我们自己对开展“II期筛选试验”可能性的探索，即在这种试验中，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），对实验方案与标准治疗进行初步的、非确定性的随机比较（最好使用中间终点），以便在样本量保持受限的情况下，目标治疗获益可能是合适的。如果进行确定性III期试验的能力能够得到保障，并且如果研究人员认为通过明智地选择假阳性概率、假阴性概率和目标治疗效果的大小，他们能够适当地平衡筛选出无用方案与可靠地检测出有用方案这两个相互冲突的需求，那么II期筛选试验设计可能适合应用。
