Jafari Peyman, Ayatollahi Seyyed Mohammad Taghi, Behboodian Javad
Department of Biostatistics and Epidemiology, Faculty of Health, Shiraz University of Medical Sciences, Shiraz, Iran.
BMC Med Res Methodol. 2006 Jan 13;6:1. doi: 10.1186/1471-2288-6-1.
In clinical trials, both unequal randomization design and sequential analyses have ethical and economic advantages. In the single-stage-design (SSD), however, if the sample size is not adjusted based on unequal randomization, the power of the trial will decrease, whereas with sequential analysis the power will always remain constant. Our aim was to compare sequential boundaries approach with the SSD when the allocation ratio (R) was not equal.
We evaluated the influence of R, the ratio of the patients in experimental group to the standard group, on the statistical properties of two-sided tests, including the two-sided single triangular test (TT), double triangular test (DTT) and SSD by multiple simulations. The average sample size numbers (ASNs) and power (1-beta) were evaluated for all tests.
Our simulation study showed that choosing R = 2 instead of R = 1 increases the sample size of SSD by 12% and the ASN of the TT and DTT by the same proportion. Moreover, when R = 2, compared to the adjusted SSD, using the TT or DTT allows to retrieve the well known reductions of ASN observed when R = 1, compared to SSD. In addition, when R = 2, compared to SSD, using the TT and DTT allows to obtain smaller reductions of ASN than when R = 1, but maintains the power of the test to its planned value.
This study indicates that when the allocation ratio is not equal among the treatment groups, sequential analysis could indeed serve as a compromise between ethicists, economists and statisticians.
在临床试验中，不等随机化设计和序贯分析都具有伦理和经济优势。然而，在单阶段设计（SSD）中，如果样本量未根据不等随机化进行调整，试验效能将会降低，而采用序贯分析时效能将始终保持不变。我们的目的是在分配比（R）不相等时，比较序贯界值法与单阶段设计。
我们通过多次模拟评估了实验组与标准组患者比例R对双侧检验统计特性的影响，包括双侧单三角检验（TT）、双三角检验（DTT）和单阶段设计。对所有检验评估了平均样本量数（ASN）和效能（1-β）。
我们的模拟研究表明，选择R = 2而非R = 1会使单阶段设计的样本量增加12%，三角检验和双三角检验的平均样本量数也增加相同比例。此外，当R = 2时，与调整后的单阶段设计相比，使用三角检验或双三角检验可恢复在R = 1时相对于单阶段设计观察到的平均样本量数的显著减少。此外，当R = 2时，与单阶段设计相比，使用三角检验和双三角检验可获得比R = 1时更小的平均样本量数减少，但保持检验效能在其计划值。
本研究表明，当各治疗组间分配比不相等时，序贯分析确实可以成为伦理学家、经济学家和统计学家之间的一种折衷方案。
