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1.
Proportional hazards are a common assumption when designing confirmatory clinical trials in oncology. This assumption not only affects the analysis part but also the sample size calculation. The presence of delayed effects causes a change in the hazard ratio while the trial is ongoing since at the beginning we do not observe any difference between treatment arms, and after some unknown time point, the differences between treatment arms will start to appear. Hence, the proportional hazards assumption no longer holds, and both sample size calculation and analysis methods to be used should be reconsidered. The weighted log‐rank test allows a weighting for early, middle, and late differences through the Fleming and Harrington class of weights and is proven to be more efficient when the proportional hazards assumption does not hold. The Fleming and Harrington class of weights, along with the estimated delay, can be incorporated into the sample size calculation in order to maintain the desired power once the treatment arm differences start to appear. In this article, we explore the impact of delayed effects in group sequential and adaptive group sequential designs and make an empirical evaluation in terms of power and type‐I error rate of the of the weighted log‐rank test in a simulated scenario with fixed values of the Fleming and Harrington class of weights. We also give some practical recommendations regarding which methodology should be used in the presence of delayed effects depending on certain characteristics of the trial. 相似文献
2.
Comparison of Four New General Classes of Search Designs 总被引:1,自引:0,他引:1
A factor screening experiment identifies a few important factors from a large list of factors that potentially influence the response. If a list consists of m factors each at three levels, a design is a subset of all possible 3 m runs. This paper considers the problem of finding designs with small numbers of runs, using the search linear model introduced in Srivastava (1975). The paper presents four new general classes of these 'search designs', each with 2 m −1 runs, which permit, at most, two important factors out of m factors to be searched for and identified. The paper compares the designs for 4 ≤ m ≤ 10, using arithmetic and geometric means of the determinants, traces and maximum characteristic roots of particular matrices. Two of the designs are found to be superior in all six criteria studied. The four designs are identical for m = 3 and this design is an optimal design in the class of all search designs under the six criteria. The four designs are also identical for m = 4 under some row and column permutations. 相似文献
3.
The problem considered is that of finding an optimum measurement schedule to estimate population parameters in a nonlinear model when the patient effects are random. The paper presents examples of the use of sensitivity functions, derived from the General Equivalence Theorem for D-optimality, in the construction of optimum population designs for such schedules. With independent observations, the theorem applies to the potential inclusion of a single observation. However, in population designs the observations are correlated and the theorem applies to the inclusion of an additional measurement schedule. In one example, three groups of patients of differing size are subject to distinct schedules. Numerical, as opposed to analytical, calculation of the sensitivity function is advocated. The required covariances of the observations are found by simulation. 相似文献
4.
For a wide variety of applications, experiments are based on units ordered over time or space. Models for these experiments generally may include one or more of: correlations, systematic trends, carryover effects and interference effects. Since the standard optimal block designs may not be efficient in these situations, orthogonal arrays of type I and type II, which were introduced in 1961 by C.R. Rao [Combinatorial arrangements analogous to orthogonal arrays, Sankhya A 23 (1961) 283–286], have been recently used to construct optimal and efficient designs for many of these experiments. Results in this area are unified and the salient features are outlined. 相似文献
5.
Complete and partial diallel cross designs are examined as to their construction and robustness against the loss of a block of observations. A simple generalized inverse is found for the information matrix of the line effects, which allows evaluation of expressions for the variances of the line-effect differences with and without the missing block. A-efficiencies, based on average variances of the elementary contrasts of the line-effects, suggest that these designs are fairly robust. The loss of efficiency is generally less than 10%, but it is shown that specific comparisons might suffer a loss of efficiency of as much as 40%. 相似文献
6.
通过构造几类图的最大独立集,给出了它们的分数染色数的下界;再通过构造具有该下界值的分数染色,给出了这几类循环图的分数染色数的上界,于是就确定了它们的分数染色数. 相似文献
7.
孙国敏 《湛江师范学院学报》2002,23(3):29-34
DNA分子近邻互补链碱基的非线性动力学效应研究,综述了Yomosa及Zhang模型,并在改进后的平面转子模型基础上,利用阶乘矩分析方法分析了平面转子模型的非线性效应,结果说明该模型更好的近似性. 相似文献
8.
特征提取是手写体数字识别研究中的重要问题,有效、稳定的特征是提高识别率和识别精度的关键。该文提出了一种基于分数本征特征和核非线性分类器的手写数字识别方法,首先找到时频平面的一个轴进行分数傅里叶变换,使不同类别样本在这个轴上最大限度地分开,然后用主元分析进行降维,得到比较稳健的低维特征,再将常用分类器用于特征分类,实现对手写数字的识别。对实际数据进行实验,结果表明上述本征特征与核非线性分类器相结合有较高的识别率和训练、分类效率。 相似文献
9.
To explore the projection efficiency of a design, Tsai, et al [2000. Projective three-level main effects designs robust to model uncertainty. Biometrika 87, 467–475] introduced the Q criterion to compare three-level main-effects designs for quantitative factors that allow the consideration of interactions in addition to main effects. In this paper, we extend their method and focus on the case in which experimenters have some prior knowledge, in advance of running the experiment, about the probabilities of effects being non-negligible. A criterion which incorporates experimenters’ prior beliefs about the importance of each effect is introduced to compare orthogonal, or nearly orthogonal, main effects designs with robustness to interactions as a secondary consideration. We show that this criterion, exploiting prior information about model uncertainty, can lead to more appropriate designs reflecting experimenters’ prior beliefs. 相似文献
10.
This paper studies optimum designs for linear models when the errors are heteroscedastic. Sufficient conditions are given
in order to obtainD-, A- andE-optimum designs for a complete regression model from partial optimum designs for some sub-parameters. A result about optimality
for a complete model from the optimality for the submodels is included.
Supported by Junta de Andalucía, research group FQM244. 相似文献