Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420, USA.
Stat Med. 2009 Oct 30;28(24):2941-51. doi: 10.1002/sim.3684.
Proof-of-concept in clinical trials has traditionally focused on the identification of a maximum tolerated dose with the assumption that the higher doses provide better efficacy. However, adverse events associated with a maximum tolerated dose may have a negative effect on efficacy. We present an efficient adaptive dose-finding strategy that concentrates patient assignments at and around the dose which has the best efficacy/tolerability profile based on a utility function. The strategy is applied within the setting of a crossover design. While the strategy may also be applied to parallel studies, a crossover design provides more power for a given sample size for comparisons between the optimal dose versus placebo and/or active control when it is reasonable to assume no carryover effects.
临床试验中的概念验证传统上侧重于确定最大耐受剂量，假设较高剂量会提供更好的疗效。然而，与最大耐受剂量相关的不良事件可能会对疗效产生负面影响。我们提出了一种有效的自适应剂量发现策略，该策略基于效用函数，将患者分配集中在具有最佳疗效/耐受性特征的剂量附近和剂量上。该策略适用于交叉设计的环境中。虽然该策略也可应用于平行研究，但当合理假设无交叉效应时，交叉设计在比较最佳剂量与安慰剂和/或活性对照时，可在给定样本量下提供更多的效能。
