Shift models for dose-finding in partially ordered groups.
Shift models for dose-finding in partially ordered groups.
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DOI：
10.1177/1740774518801599
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Conaway MR
中科院分区：
文献类型：
--
作者：
Horton BJ;Wages NA;Conaway MR
对于需要分组特定剂量选择的剂量发现临床试验，可供选择的选项有限。虽然对组进行平行试验是一种可用于组特定剂量选择的方法，但这种方法允许选择与临床有意义的组顺序信息不一致的最大耐受剂量选择。两阶段连续重新评估方法是为涉及三组或更多组的研究中的剂量发现而开发的，其中一些组而不是所有组之间的组脆弱顺序是已知的，从而产生偏序。这是对现有连续重估方法的扩展，即两个有序组的移位模型。这种方法允许按组选择剂量，其中最大耐受剂量选择遵循组之间已知的脆弱顺序。例如，如果已知某一组最虚弱，则该组的推荐最大耐受量不应超过为任何其他组推荐的最大耐受量。在偏序组中剂量发现的选择有限的情况下，将该方法与两种选择进行比较：1)现有的偏序组中剂量发现的方法，其计算可访问性较低；2)使用两阶段连续重新评估方法对每组进行独立试验。模拟研究表明，当忽略有关群体脆弱性的信息时，使用独立的连续重新评估方法进行分组试验，30%的模拟会导致组间最大耐受剂量的选择是无序的。此外，与在每个组内使用独立的连续重新评估方法试验相比，偏序分组的两阶段连续重新评估方法选择最大耐受剂量的频率更高，并将更多的患者分配到最大耐受剂量。仿真结果表明，该方法与计算量较小的方法具有相似的仿真结果。所提出的偏序分组的持续重新评估方法确保了适当的最大耐受剂量顺序，并提高了最大耐受剂量选择的准确性，同时允许通过计算可访问的试验实施。
Limited options are available for dose finding clinical trials requiring group specific dose selection. While conducting parallel trials for groups is an accessible approach to group specific dose selection, this approach allows for maximum tolerated dose selection that does not align with clinically meaningful group order information. The two-stage continual reassessment method is developed for dose-finding in studies involving three or more groups where group frailty order is known between some but not all groups, creating a partial order. This is an extension of the existing continual reassessment method shift model for two ordered groups. This method allows for dose selection by group, where maximum tolerated dose selection follows the known frailty order among groups. For example, if a group is known to be the most frail, the recommended maximum tolerated dose for this group should not exceed the maximum tolerated dose recommended for any other group. With limited alternatives for dose finding in partially ordered groups, this method is compared to two alternatives: 1) an existing method for dose finding in partially ordered groups which is less computationally accessible and 2) independent trials for each group using the two-stage continual reassessment method. Simulation studies show that when ignoring information on group frailty, using independent continual reassessment method trials by group, 30% of simulations would result in maximum tolerated dose selection that is out of order between groups. In addition, the two-stage continual reassessment method for partially ordered groups selects the maximum tolerated dose more often and assigns more patients to the maximum tolerated dose compared to using independent continual reassessment method trials within each group. Simulation results for the proposed method and the less computationally accessible approach are similar. The proposed continual reassessment method for partially ordered groups ensures appropriate maximum tolerated dose order and improves accuracy of maximum tolerated dose selection, while allowing for trial implementation that is computationally accessible.
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与持续重新评估方法相反，基于毒性概率间隔设计的性能。
影响因子：
2
作者：
Horton BJ;Wages NA;Conaway MR
通讯作者：
Conaway MR
I阶段试验的设计完全或部分有序的组。
影响因子：
2
作者：
Conaway MR
通讯作者：
Conaway MR
DOI：
10.1177/1740774517722760
发表时间：
2017-10
期刊：
Clinical trials (London, England)
影响因子：
--
作者：
Conaway M
通讯作者：
Conaway M
影响因子：
2
作者：
Conaway, Mark R.;Wages, Nolan A.
通讯作者：
Wages, Nolan A.
影响因子：
1.9
作者：
O'Quigley, J;Paoletti, X
通讯作者：
Paoletti, X