Properties of the weighted log‐rank test in the design of confirmatory studies with delayed effects

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.     

Comparison of Four New General Classes of Search Designs

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.     

Examples of the use of an equivalence theorem in constructing optimum experimental designs for random-effects nonlinear regression models

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.     

Efficient designs based on orthogonal arrays of type I and type II for experiments using units ordered over time or space

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.     

Robustness of a Class of Partial Diallel Cross Designs to the Unavailability of a Complete Block of Observations

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%.     

“方块布依字”及其在布依族宗教典籍传承过程中的作用

“方块布依字”是布依族民间流传的一种仿汉字的记音符号 ,主要通行于宗教职业者群体。布依族宗教经文手抄本中的用字和造字方法主要有四种 ,或用与布依语相同或相近的音来记录该语音 ,或根据布依语词义、用汉语方块字的字符重新造字 ,或用与布依语同义的词来记录 ,或直接用汉字本身来记录。“方块布依字”在布依族宗教典籍及传统文化的传承过程中具有重要的作用。     

On Block Updating in Markov Random Field Models for Disease Mapping

Gaussian Markov random field (GMRF) models are commonly used to model spatial correlation in disease mapping applications. For Bayesian inference by MCMC, so far mainly single-site updating algorithms have been considered. However, convergence and mixing properties of such algorithms can be extremely poor due to strong dependencies of parameters in the posterior distribution. In this paper, we propose various block sampling algorithms in order to improve the MCMC performance. The methodology is rather general, allows for non-standard full conditionals, and can be applied in a modular fashion in a large number of different scenarios. For illustration we consider three different applications: two formulations for spatial modelling of a single disease (with and without additional unstructured parameters respectively), and one formulation for the joint analysis of two diseases. The results indicate that the largest benefits are obtained if parameters and the corresponding hyperparameter are updated jointly in one large block. Implementation of such block algorithms is relatively easy using methods for fast sampling of Gaussian Markov random fields ( Rue, 2001 ). By comparison, Monte Carlo estimates based on single-site updating can be rather misleading, even for very long runs. Our results may have wider relevance for efficient MCMC simulation in hierarchical models with Markov random field components.     

中西典型思维方式与汉英文字音形意关联

文章指出文字与民族思维方式跨文化研究中的不足 ,扼要分析了潜在的成因 ,着重探讨比较了中西民族典型思维 (西方二元分析思维与汉民族整体思维 )在西方字母文字 (以英文为例 )与汉字音、形两大物质特性与意义概念结合上的反映 ,认为正确对待文字与思维之间的客观关联 ,不仅能从新的角度审视文字功能 ,而且有利于我们从中认识和挖掘各民族历史文化的深厚积淀 ,促进跨文化交流的全面开展     

矩阵非奇异性判定

本文利用矩阵块对角占优的性质,给出矩阵非奇异的一个判定条件     

对参加“步步高杯“全国女排联赛运动队拦网状况的比较研究

通过对2004~2005和2005~2006两个赛季的女子“步步高杯”全国联赛中的拦网状况分析和研究,指出了栏网存在的主要问题,并提出了合理化的建议。