Berger Vance W, Bejleri Klejda, Agnor Rebecca
Biometry Research Group, National Cancer Institute, 9609 Medical Center Drive, Rockville, 20850, MD, U.S.A.
University of Maryland, Baltimore County, Baltimore, MD, U.S.A.
Stat Med. 2016 Feb 28;35(5):685-94. doi: 10.1002/sim.6637. Epub 2015 Sep 3.
Randomization is one of the cornerstones of the randomized clinical trial, and there is no shortage of methods one can use to randomize patients to treatment groups. When deciding which one to use, researchers must bear in mind that not all randomization procedures are equally adept at achieving the objective of randomization, namely, balanced treatment groups. One threat is chronological bias, and permuted blocks randomization does such a good job at controlling chronological bias that it has become the standard randomization procedure in clinical trials. But permuted blocks randomization is especially vulnerable to selection bias, so as a result, the maximum tolerated imbalance (MTI) procedures were proposed as better alternatives. In comparing the procedures, we have somewhat of a false controversy, in that actual practice goes uniformly one way (permuted blocks), whereas scientific arguments go uniformly the other way (MTI procedures). There is no argument in the literature to suggest that the permuted block design is better than or even as good as the MTI procedures, but this dearth is matched by an equivalent one regarding actual trials using the MTI procedures. So the 'controversy', if we are to call it that, pits misguided precedent against sound advice that tends to be ignored in practice. We shall review the issues to determine scientifically which of the procedures is better and, therefore, should be used.
随机化是随机临床试验的基石之一，可用于将患者随机分配到治疗组的方法并不匮乏。在决定使用哪种方法时，研究人员必须牢记，并非所有随机化程序在实现随机化目标（即均衡的治疗组）方面都同样出色。一个威胁是时间顺序偏差，而置换块随机化在控制时间顺序偏差方面做得非常好，以至于它已成为临床试验中的标准随机化程序。但置换块随机化特别容易受到选择偏差的影响，因此，最大耐受不平衡（MTI）程序被提议作为更好的替代方案。在比较这些程序时，我们存在某种虚假的争议，因为实际操作统一采用一种方式（置换块），而科学论据则统一采用另一种方式（MTI程序）。文献中没有论据表明置换块设计优于甚至等同于MTI程序，但在实际使用MTI程序的试验方面，同样缺乏相关内容。所以，如果我们要称之为“争议”的话，它是将误导性的先例与在实践中往往被忽视的合理建议对立起来。我们将审视这些问题，以科学地确定哪种程序更好，从而应该被使用。
