Amgen Inc., 1150 Veterans Blvd., South San Francisco, CA 94080, USA.
Stat Med. 2011 Oct 30;30(24):2881-9. doi: 10.1002/sim.4351. Epub 2011 Sep 8.
Stratification is common in clinical trials because it can reduce the variance of the estimated treatment effect. The traditional demonstration of variance reduction relies on the assumption of stratum sizes being fixed quantities. However, in practice, to speed up enrollment, and to obtain a study population with a similar distribution as the overall population, the stratum sizes are allowed to vary. Under the condition that the total sample size is fixed and that the stratum sizes have a multinomial distribution, the criterion changes for achieving a reduction in variance. The relationship between the stratified and unstratified variances is established and shown to be approximately the same for prestratified and post-stratified trials. It is demonstrated why stratification may actually increase the variance compared with no stratification even when the mean square error is reduced on account of stratification. Data from a real clinical trial will be used for illustration. The benefit attributed to stratification needs to be re-examined in light of the findings presented, particularly given its widespread use.
分层在临床试验中很常见，因为它可以减少估计治疗效果的方差。传统的方差减少证明依赖于分层大小是固定数量的假设。然而，在实践中，为了加快入组速度，并获得与总体人群分布相似的研究人群，允许分层大小发生变化。在总样本量固定且分层大小具有多项分布的条件下，实现方差减少的标准会发生变化。建立了分层和不分层方差之间的关系，并表明对于预分层和后分层试验，它们大致相同。证明了为什么即使由于分层而降低了均方误差，与不分层相比，分层实际上可能会增加方差。将使用来自真实临床试验的数据进行说明。鉴于分层的广泛应用，需要根据提出的结果重新检查归因于分层的益处。
