Capra William B
Department of Biostatistics and Clinical Data Management, Chiron Corporation, 4560 Horton Street, M/S U-120, Emeryville, CA 94608-2916, USA.
Control Clin Trials. 2004 Apr;25(2):168-77. doi: 10.1016/j.cct.2003.11.005.
The discontinuation design has been proposed as an alternative to the classic randomized design for evaluating the effect of an experimental agent on time-to-disease progression and survival duration. With this design, all enrolled patients are treated with an experimental agent for a fixed course of therapy. Those patients with progressive disease at or before the end of this fixed period are removed from trial while those with stable disease or better are randomized to continued treatment with the experimental agent or standard of care. Simulations presented in this paper demonstrate that for realistic situations, the loss in information on patients enrolled but not randomized in the discontinuation design is of sufficient magnitude that it is underpowered as compared to the classic design of randomizing all enrolled subjects.
为评估实验药物对疾病进展时间和生存时间的影响，有人提出采用中断设计作为经典随机设计的替代方案。采用这种设计时，所有入组患者均接受固定疗程的实验药物治疗。在这个固定疗程结束时或之前出现疾病进展的患者退出试验，而疾病稳定或病情更好的患者则随机分为继续接受实验药物治疗或接受标准治疗。本文给出的模拟结果表明，在实际情况下，中断设计中未被随机分组的入组患者信息损失量足够大，以至于与将所有入组受试者进行随机分组的经典设计相比，其检验效能不足。
