Statistical testing strategies for assessing treatment efficacy and marker accuracy in phase III trials

When a candidate predictive marker is available, but evidence on its predictive ability is not sufficiently reliable, all‐comers trials with marker stratification are frequently conducted. We propose a framework for planning and evaluating prospective testing strategies in confirmatory, phase III marker‐stratified clinical trials based on a natural assumption on heterogeneity of treatment effects across marker‐defined subpopulations, where weak rather than strong control is permitted for multiple population tests. For phase III marker‐stratified trials, it is expected that treatment efficacy is established in a particular patient population, possibly in a marker‐defined subpopulation, and that the marker accuracy is assessed when the marker is used to restrict the indication or labelling of the treatment to a marker‐based subpopulation, ie, assessment of the clinical validity of the marker. In this paper, we develop statistical testing strategies based on criteria that are explicitly designated to the marker assessment, including those examining treatment effects in marker‐negative patients. As existing and developed statistical testing strategies can assert treatment efficacy for either the overall patient population or the marker‐positive subpopulation, we also develop criteria for evaluating the operating characteristics of the statistical testing strategies based on the probabilities of asserting treatment efficacy across marker subpopulations. Numerical evaluations to compare the statistical testing strategies based on the developed criteria are provided.     

Heteroscedastic Global Tests that the Regression Parameters for Two or More Independent Groups are Identical

Simulation results are reported on methods that allow both within group and between group heteroscedasticity when testing the hypothesis that independent groups have identical regression parameters. The methods are based on a combination of extant techniques, but their finite-sample properties have not been studied. Included are results on the impact of removing all leverage points or just bad leverage points. The method used to identify leverage points can be important and can improve control over the Type I error probability. Results are illustrated using data from the Well Elderly II study.     

在位相空间中求解外力含时的受迫量子谐振子

运用广义线性量子变换理论 ,在位相空间中通过算子的代数运算求解外力含时的受迫谐振子 ,给出了演化算子、演化算子矩阵元和波函数的表示式 .     

我国高校文科学报的“当代化”论

高校文科学报的“当代化”是相对于时下盛行的“现代化”而言的。它是根据我国高校文科学报的发生及其发展历程的阶段性特征 ,以及“当代化”所蕴涵的人类文明进程的阶段性定位和“与时俱进”的时代性体现的科学内涵而提出来的。“当代化”具有现实性和求真性的鲜明特征 ,对于 2 1世纪我国高校文科学报的发展是一种求真务实的选择。     

律师在侦查阶段的诉讼地位和作用

律师在侦查阶段介入刑事诉讼不享有辩护人的独立诉讼地位 ,其法律行为具有法律帮助性质 ,主要为犯罪嫌疑人提供法律咨询 ,代理申诉、控告和为犯罪嫌疑人申请取保候审等。这种界定不仅有利于明确律师在侦查阶段的职责 ,也有利于打消认为律师介入侦查将带来太多负效应的顾虑。     

Computing maximum likelihood estimates from type II doubly censored exponential data

It is well-known that, under Type II double censoring, the maximum likelihood (ML) estimators of the location and scale parameters, θ and δ, of a twoparameter exponential distribution are linear functions of the order statistics. In contrast, when θ is known, theML estimator of δ does not admit a closed form expression. It is shown, however, that theML estimator of the scale parameter exists and is unique. Moreover, it has good large-sample properties. In addition, sharp lower and upper bounds for this estimator are provided, which can serve as starting points for iterative interpolation methods such as regula falsi. Explicit expressions for the expected Fisher information and Cramér-Rao lower bound are also derived. In the Bayesian context, assuming an inverted gamma prior on δ, the uniqueness, boundedness and asymptotics of the highest posterior density estimator of δ can be deduced in a similar way. Finally, an illustrative example is included.     

ispLSI1016在数字锁相环中的应用

讨论了采用ispLSI1 0 1 6构造数字锁相环的基本方法 ,并给出了分频器、相位比较器和吞脉冲计数器的相应的编码指令     

Empirical Non-Parametric Control Charts: Estimation Effects and Corrections

Owing to the extreme quantiles involved, standard control charts are very sensitive to the effects of parameter estimation and non-normality. More general parametric charts have been devised to deal with the latter complication and corrections have been derived to compensate for the estimation step, both under normal and parametric models. The resulting procedures offer a satisfactory solution over a broad range of underlying distributions. However, situations do occur where even such a large model is inadequate and nothing remains but to consider non- parametric charts. In principle, these form ideal solutions, but the problem is that huge sample sizes are required for the estimation step. Otherwise the resulting stochastic error is so large that the chart is very unstable, a disadvantage that seems to outweigh the advantage of avoiding the model error from the parametric case. Here we analyse under what conditions non-parametric charts actually become feasible alternatives for their parametric counterparts. In particular, corrected versions are suggested for which a possible change point is reached at sample sizes that are markedly less huge (but still larger than the customary range). These corrections serve to control the behaviour during in-control (markedly wrong outcomes of the estimates only occur sufficiently rarely). The price for this protection will clearly be some loss of detection power during out-of-control. A change point comes in view as soon as this loss can be made sufficiently small.     

第二次世界大战对世界格局产生的影响

第二次世界大战以雅尔塔体系为基础形成了以美苏两大国为首的世界政治格局,对战后世界政治、经济和国际关系产生了深刻影响。随着两极格局的终结,世界又朝着多极化趋势发展。     

非拓扑孤子模型的相变特征与袋常数的温度依赖性

本文计算了在有限温度和密度下非拓扑孤子模型的有效势;得到了袋常数对温度和化学势的依赖关系;分析了禁闭解除相变的特征.结果表明:该模型的禁闭解除相变为一级;相变特征的分析表明有退禁闭相与禁闭相的两相共存.