Institute of Medical Biometry and Informatics, University of Heidelberg, Heidelberg, Germany.
Stat Med. 2012 Dec 10;31(28):3579-96. doi: 10.1002/sim.5461. Epub 2012 Jul 4.
In the three-arm 'gold standard' non-inferiority design, an experimental treatment, an active reference, and a placebo are compared. This design is becoming increasingly popular, and it is, whenever feasible, recommended for use by regulatory guidelines. We provide a general method to calculate the required sample size for clinical trials performed in this design. As special cases, the situations of continuous, binary, and Poisson distributed outcomes are explored. Taking into account the correlation structure of the involved test statistics, the proposed approach leads to considerable savings in sample size as compared with application of ad hoc methods for all three scale levels. Furthermore, optimal sample size allocation ratios are determined that result in markedly smaller total sample sizes as compared with equal assignment. As optimal allocation makes the active treatment groups larger than the placebo group, implementation of the proposed approach is also desirable from an ethical viewpoint.
在三臂“金标准”非劣效性设计中，比较了一种实验性治疗、一种活性对照和安慰剂。这种设计越来越受欢迎，并且只要可行，监管指南就推荐使用。我们提供了一种通用方法来计算在这种设计中进行的临床试验所需的样本量。作为特例，探索了连续、二项和泊松分布结果的情况。考虑到所涉及的检验统计量的相关结构，与所有三个尺度水平应用特定方法相比，所提出的方法可显著节省样本量。此外，确定了最优的样本量分配比例，与均等分配相比，这导致明显更小的总样本量。由于最优分配使活性治疗组大于安慰剂组，因此从伦理角度来看，实施所提出的方法也是可取的。
