Supplementary analysis of probabilities at the termination of a group sequential phase II trial
Supplementary analysis of probabilities at the termination of a group sequential phase II trial
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DOI：
10.1002/sim.1990
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发表时间：
2005-04-15
影响因子：
2
通讯作者：
Gehan, E
中科院分区：
文献类型：
--
作者：
Liu, AY;Wu, CQ;Gehan, E
我们考虑组序11期试验结束后各种概率的估计。一个鼓舞人心的例子是，11期肿瘤试验的停止规则完全是根据对药物治疗的反应来确定的，在试验结束时估计毒性和反应的比率是可取的。传统的概率的最大似然估计量（样本比例）是有偏的，并提出了两个替代估计量来纠正偏差，一个是使用Whitehead的偏校正方法得到的偏减少估计量，一个是来自Rao-Blackwell条件反射方法的无偏估计量。这三种估计方法在偏置上都具有一定的不变性。此外，概率估计值及其偏差和精度可以通过观察到的响应率和试验停止的阶段来评估，从而避免了大量的计算。版权所有2004 John Wiley W Sons， Ltd。
We consider estimation of various probabilities after termination of a group sequential phase 11 trial. A motivating example is that the stopping rule of a phase 11 oncologic trial is determined solely based on response to a drug treatment, and at the end of the trial estimating the rate of toxicity and response is desirable. The conventional maximum likelihood estimator (sample proportion) of a probability is shown to be biased, and two alternative estimators are proposed to correct for bias, a bias-reduced estimator obtained by using Whitehead's bias-adjusted approach, and an unbiased estimator from the Rao-Blackwell method of conditioning. All three estimation procedures are shown to have certain invariance property in bias. Moreover, estimators of a probability and their bias and precision can be evaluated through the observed response rate and the stage at which the trial stops, thus avoiding extensive computation. Copyright (c) 2004 John Wiley W Sons, Ltd.