Department of Biostatistics, University of Washington, Seattle, WA 98195, USA.
Stat Med. 2010 Nov 30;29(27):2769-80. doi: 10.1002/sim.4053.
After a non-inferiority clinical trial, a new therapy may be accepted as effective, even if its treatment effect is slightly smaller than the current standard. It is therefore possible that, after a series of trials where the new therapy is slightly worse than the preceding drugs, an ineffective or harmful therapy might be incorrectly declared efficacious; this is known as 'bio-creep'. Several factors may influence the rate at which bio-creep occurs, including the distribution of the effects of the new agents being tested and how that changes over time, the choice of active comparator, the method used to account for the variability of the estimate of the effect of the active comparator, and changes in the effect of the active comparator from one trial to the next (violations of the constancy assumption). We performed a simulation study to examine which of these factors might lead to bio-creep and found that bio-creep was rare, except when the constancy assumption was violated.
在一项非劣效性临床试验后，即使新疗法的治疗效果略小于现有标准，也可能被认为是有效的。因此，在一系列新疗法略逊于前一种药物的试验之后，一种无效或有害的疗法可能会被错误地宣布为有效；这被称为“生物渐进”。有几个因素可能会影响生物渐进的速度，包括正在测试的新药物的效果分布以及随着时间的推移如何变化，活性对照药物的选择，用于解释活性对照药物效果估计的可变性的方法，以及活性对照药物从一个试验到下一个试验的效果变化（恒常性假设的违反）。我们进行了一项模拟研究，以检验这些因素中哪些可能导致生物渐进，并发现除了恒常性假设被违反的情况外，生物渐进很少发生。
