Ivanova Anastasia, Flournoy Nancy
Associate Professor, Department of Biostatistics, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7420.
Stat Biopharm Res. 2009 Feb 1;1(1):101. doi: 10.1198/sbr.2009.0010.
We compare several decision rules for allocating subjects to dosages that are based on sequential isotonic estimates of a monotone dose-toxicity curve. We conclude that the decision rule in which the next assignment is to the dose having probability of toxicity closest to target does not work well. The best rule in our comparison is given by the cumulative cohort design. According to this design, the dose for the next subject is decreased, increased, or repeated depending on the distance between the estimated toxicity rate at the current dose and the target quantile.
我们比较了几种基于单调剂量-毒性曲线的序贯等渗估计将受试者分配到不同剂量的决策规则。我们得出结论,下一次分配到毒性概率最接近目标值的剂量的决策规则效果不佳。我们比较中最佳的规则由累积队列设计给出。根据此设计,下一个受试者的剂量根据当前剂量下估计的毒性率与目标分位数之间的距离而降低、增加或重复。