Department of Mathematical Sciences, Chalmers University of Technology and Göteborg University, Göteborg, Sweden.
Stat Med. 2013 May 10;32(10):1661-76. doi: 10.1002/sim.5632. Epub 2012 Sep 30.
Many potential new medicines fail in phase III clinical trials, because of either insufficient efficacy or intolerability. Such failures may be caused by the absence of an effect and also if a suboptimal dose is being tested. It is thus important to consider how to optimise the choice of dose or doses that continue into the confirmatory phase. For many indications, it is common to test one single active dose in phase III. However, phase IIB dose-finding trials are relatively small and often lack the ability of precisely estimating the dose-response curves for efficacy and tolerability. Because of this uncertainty in dose response, it is reasonable to consider bringing more than one dose into phase III. Using simple but illustrative models, we find the optimal doses and compare the probability of success, for fixed total sample sizes, when one or two active doses are included in phase III.
许多有潜力的新药在 III 期临床试验中失败，要么是因为疗效不足，要么是因为无法耐受。这种失败可能是由于缺乏效果引起的，如果正在测试的剂量不是最佳剂量，也可能导致失败。因此，如何优化选择进入确证阶段的剂量或剂量非常重要。对于许多适应证，在 III 期临床试验中通常只测试一个单一组分的活性剂量。然而，IIIB 期剂量探索试验相对较小，通常缺乏精确估计疗效和耐受性的剂量-反应曲线的能力。由于剂量反应的这种不确定性，考虑在 III 期临床试验中引入多种剂量是合理的。我们使用简单但具有说明性的模型，在固定的总样本量下，当 III 期临床试验中包含一个或两个活性剂量时，找到最佳剂量并比较成功的概率。
