What inference for two-stage phase II trials?
What inference for two-stage phase II trials?
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DOI：
10.1186/1471-2288-12-117
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发表时间：
2012-08-06
影响因子：
4
通讯作者：
Desseaux K
中科院分区：
文献类型：
--
作者：
Porcher R;Desseaux K
西蒙的两阶段设计被广泛用于癌症II期试验。这些方法依赖于统计测试，因此允许控制I类和II类错误率，同时考虑到中期分析。然而，在这样的试验之后进行估计并不是一帆风顺的，而且已经提出了几种不同的方法。回顾了不同的点和可信区间估计方法，以及p值的计算方法，并对一系列可信的试验进行了比较。在试验中招募的患者的实际数量与预先计划的样本量不同的情况也被考虑在内。对于点估计，在实际样本量为计划的情况下，一致最小方差无偏估计(UMVUE)和偏差修正估计具有更好的性能。对于置信度区间，与所谓的“确切”置信度区间相比，使用Mate-p方法得到的覆盖概率更接近名义水平。当实际样本量不同于预先计划的样本量时，UMVUE的表现并不比专门为这种情况开发的估计器差。分析的条件是已经进行到第二阶段，需要适应的分析方法，并且可以使用一致最小方差条件估计(UMVCUE)，当第二阶段的样本量与计划的样本量略有不同时，该估计也表现良好。可以推荐使用UMVUE，因为当实际招募的患者数量等于或不同于预先计划的值时，它都表现出良好的特性。在试验没有因无效而提前停止的情况下限制分析可能是有价值的，在这种情况下可以建议使用UMVCUE。
Simon’s two-stage designs are widely used for cancer phase II trials. These methods rely on statistical testing and thus allow controlling the type I and II error rates, while accounting for the interim analysis. Estimation after such trials is however not straightforward, and several different approaches have been proposed. Different approaches for point and confidence intervals estimation, as well as computation of p-values are reviewed and compared for a range of plausible trials. Cases where the actual number of patients recruited in the trial differs from the preplanned sample size are also considered. For point estimation, the uniformly minimum variance unbiased estimator (UMVUE) and the bias corrected estimator had better performance than the others when the actual sample size was as planned. For confidence intervals, using a mid-p approach yielded coverage probabilities closer to the nominal level as compared to so-called ’exact’ confidence intervals. When the actual sample size differed from the preplanned sample size the UMVUE did not perform worse than an estimator specifically developed for such a situation. Analysis conditional on having proceeded to the second stage required adapted analysis methods, and a uniformly minimum variance conditional estimator (UMVCUE) can be used, which also performs well when the second stage sample size is slightly different from planned. The use of the UMVUE may be recommended as it exhibited good properties both when the actual number of patients recruited was equal to or differed from the preplanned value. Restricting the analysis in cases where the trial did not stop early for futility may be valuable, and the UMVCUE may be recommended in that case.
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影响因子：
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