Robust EM Continual Reassessment Method in Oncology Dose Finding.
Robust EM Continual Reassessment Method in Oncology Dose Finding.
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DOI：
10.1198/jasa.2011.ap09476
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发表时间：
2011-09-01
影响因子：
3.7
通讯作者：
Yin G
中科院分区：
文献类型：
--
作者：
Yuan Y;Yin G
The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To overcome these limitations, we naturally treat the unobserved toxicity outcomes as missing data, and use the expectation-maximization (EM) algorithm to estimate the dose toxicity probabilities based on the incomplete data to direct dose assignment. To enhance the robustness of the design, we propose prespecifying multiple sets of toxicity probabilities, each set corresponding to an individual CRM model. We carry out these multiple CRMs in parallel, across which model selection and model averaging procedures are used to make more robust inference. We evaluate the operating characteristics of the proposed robust EM-CRM designs through simulation studies and show that the proposed methods satisfactorily resolve both limitations of the CRM. Besides improving the MTD selection percentage, the new designs dramatically shorten the duration of the trial, and are robust to the prespecification of the toxicity probabilities.
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影响因子：
2.7
作者：
Jin, ZZ;Ying, ZL;Wei, LJ
通讯作者：
Wei, LJ
DOI：
10.1016/0360-3016(94)00419-l
发表时间：
1995-03-30
影响因子：
7
作者：
COIA, LR;MYERSON, RJ;TEPPER, JE
通讯作者：
TEPPER, JE
影响因子：
1.9
作者：
O'Quigley, J;Paoletti, X
通讯作者：
Paoletti, X
DOI：
10.1198/016214503000000828
发表时间：
2003-12-01
影响因子：
3.7
作者：
Hjort, NL;Claeskens, G
通讯作者：
Claeskens, G
影响因子：
2
作者：
GOODMAN, SN;ZAHURAK, ML;PIANTADOSI, S
通讯作者：
PIANTADOSI, S