Child Health Evaluative Sciences Program, The Hospital for Sick Children Research Institute, University of Toronto, Toronto, Ontario MSG 1X8, Canada.
J Clin Epidemiol. 2011 Mar;64(3):286-92. doi: 10.1016/j.jclinepi.2010.02.021. Epub 2010 Oct 6.
The study evaluated the power of the randomized placebo-phase design (RPPD)-a new design of randomized clinical trials (RCTs), compared with the traditional parallel groups design, assuming various response time distributions. In the RPPD, at some point, all subjects receive the experimental therapy, and the exposure to placebo is for only a short fixed period of time.
For the study, an object-oriented simulation program was written in R. The power of the simulated trials was evaluated using six scenarios, where the treatment response times followed the exponential, Weibull, or lognormal distributions. The median response time was assumed to be 355 days for the placebo and 42 days for the experimental drug.
Based on the simulation results, the sample size requirements to achieve the same level of power were different under different response time to treatment distributions. The scenario where the response times followed the exponential distribution had the highest sample size requirement. In most scenarios, the parallel groups RCT had higher power compared with the RPPD.
The sample size requirement varies depending on the underlying hazard distribution. The RPPD requires more subjects to achieve a similar power to the parallel groups design.
本研究评估了随机安慰剂阶段设计（RPPD）——一种新的随机临床试验（RCT）设计，与传统的平行组设计相比，假设了各种反应时间分布。在 RPPD 中，在某个时间点，所有受试者都接受实验治疗，而接受安慰剂的暴露时间仅为固定的短时间。
为此研究，我们用 R 编写了一个面向对象的模拟程序。使用六种情景评估模拟试验的功效，其中治疗反应时间遵循指数、威布尔或对数正态分布。假设安慰剂的中位反应时间为 355 天，实验药物的中位反应时间为 42 天。
根据模拟结果，在不同的治疗反应时间分布下，实现相同功效水平所需的样本量要求不同。反应时间遵循指数分布的情景需要最大的样本量要求。在大多数情况下，平行组 RCT 的功效比 RPPD 更高。
样本量要求取决于潜在的风险分布。RPPD 需要更多的受试者才能达到与平行组设计相似的功效。
