Performance of toxicity probability interval based designs in contrast to the continual reassessment method.
Performance of toxicity probability interval based designs in contrast to the continual reassessment method.
复制标题
与持续重新评估方法相反，基于毒性概率间隔设计的性能。
DOI：
10.1002/sim.7043
复制
发表时间：
2017-01-30
影响因子：
2
通讯作者：
Conaway MR
中科院分区：
文献类型：
--
作者：
Horton BJ;Wages NA;Conaway MR
毒性概率区间设计作为一种剂量测定方法近年来受到越来越多的关注。在本研究中，我们比较了两阶段、基于似然的持续重新评估方法（CRM）、改进毒性概率区间（mTPI）和贝叶斯最优区间设计（BOIN），以评估每种方法在I期试验剂量选择中的性能。我们使用了几种综合指标来比较这些方法的性能，包括真实最大耐受剂量（MTD）的正确选择百分比（PCS），患者分配到真实最大耐受剂量（MTD）及周围的剂量，以及准确性指数。该指标考虑到每个剂量水平下的真实毒性概率与目标毒性率之间的距离，是描述MTD选择和患者分配的整个分布的效率度量。模拟研究考虑了大范围的毒性曲线和不同的样本量。在考虑pc时，我们发现CRM在大多数情况下优于这两种竞争方法，其次是BOIN，然后是mTPI。在考虑剂量分配的准确性指数时，我们观察到类似的趋势，其中CRM通常优于mTPI和BOIN。这些趋势随着剂量水平的增加而更加明显。
Toxicity probability interval designs have received increasing attention as a dose-finding method in recent years. In this study, we compared the two-stage, likelihood-based continual reassessment method (CRM), modified toxicity probability interval (mTPI), and the Bayesian optimal interval design (BOIN) in order to evaluate each method's performance in dose selection for Phase I trials. We use several summary measures to compare the performance of these methods, including percentage of correct selection (PCS) of the true maximum tolerable dose (MTD), allocation of patients to doses at and around the true MTD, and an accuracy index. This index is an efficiency measure that describes the entire distribution of MTD selection and patient allocation by taking into account the distance between the true probability of toxicity at each dose level and the target toxicity rate. The simulation study considered a broad range of toxicity curves and various sample sizes. When considering PCS, we found that CRM outperformed the two competing methods in most scenarios, followed by BOIN, then mTPI. We observed a similar trend when considering the accuracy index for dose allocation, where CRM most often outperformed both the mTPI and BOIN. These trends were more pronounced with increasing number of dose levels.