Consistency of continual reassessment method under model misspecification
Consistency of continual reassessment method under model misspecification
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DOI：
10.1093/biomet/83.2.395
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发表时间：
1996-06-01
期刊：
影响因子：
2.7
通讯作者：
OQuigley, J
中科院分区：
文献类型：
--
作者：
Shen, LZ;OQuigley, J
本文研究了在I期临床试验中用于确定靶剂量水平的连续再评估方法的大样本行为。研究了一种序贯最大似然法，用于局部估计给定的靶向毒性水平。在模型错误指定的情况下，建立了极大似然估计的相合性和渐近正态分布，结果表明，总体上，推荐剂量水平将收敛于目标水平。然而，在某些情况下，推荐剂量可能会收敛到接近目标水平的水平，但不一定是最接近的水平。这与O‘Quigley，Pepe&Fisher(1990)的结论不同，我们描述了这种情况，并提供了保证收敛的条件。
This paper studies large sample behaviour of the continual reassessment method used to determine the target dose levels in phase I clinical trials. A sequential maximum likelihood procedure is investigated for local estimation of a given targeted toxicity level. Consistency and asymptotic normality for the maximum likelihood estimates are established under model misspecification and it is shown that, in general, the recommended dose level will converge to the target level. There are, however, situations in which the recommended dose may converge to a level close to the target level, but not necessarily the closest. This contrasts with the conclusions of O'Quigley, Pepe & Fisher (1990) and we describe this situation as well as providing the conditions under which convergence is assured.