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.     

Conditional time-dependent nonparametric estimators with an application to healthcare production function

ABSTRACT

By using the probabilistic framework of production efficiency, the paper develops time-dependent conditional efficiency estimators performing a non-parametric frontier analysis. Specifically, by applying both full and quantile (robust) time-dependent conditional estimators, it models the dynamic effect of health expenditure on countries’ technological change and technological catch-up levels. The results from the application reveal that the effect of per capita health expenditure on countries’ technological change and technological catch-up is nonlinear and is subject to countries’ specific income levels.     

A NOTE ON EVANESCENT PROCESSES

This note examines the connection between μ-invariant measures for the transition function of a continuous-time Markov chain and those of its q-matrix, Q. The major result establishes a necessary and aufficient condition for a convergent μ-invariant measure for Q to be μ-inhant for the minimal transition function, P, under the assumption that P is honest. This corrects Theorem 6 of Vere-Jones (1969) and the first part of Corollary 1 of Pollett (1986), both of which assert that the above conclusion holds in the absence of this condition. The error was pointed out by E.A. van Doom (1991) and the counterexample which be presented provides the basis for the present arguments. In determining where the error occurred in the original proof, we are able to identify a simple sufficient condition for μ-invariance.     

中外合作办学的现状及问题分析

文章就中外合作办学的质量、合作者的水平和资质、合作办学的监管等问题进行了分析,并提出了相应的几点对策建议。     

小波分析在管理数据处理中的应用

提出了一种基于小波变换的管理数据处理方法，把公司管理上的数据看成一个非平稳的时间序列，利用小渡函数将该时间序列分解到不同的频率通道上，然后将分解后的信号当作近似的平稳时间序列，用一些传统的统计方法进行预测，同时对中国足球彩票若干期的销售量数据进行了处理和预测，并将结果与实际销量以及用传统的AR模型的预测值进行了比较。     

与时俱进 应势而变——浅议入世后我国高等职业教育发展的趋势

入世以后,必将对我国高等职业教育提出新的要求。高等职业教育必须顺应时代发展的趋势,与时俱进、应势而变,才能与时代同步。本文遵循以下思路展开:入世以后,对我国高等职业教育的发展趋势作一些前瞻性的探讨,在此基础上提出应对的措施。有利于我国高等职业教育主动地适应新形势发展的要求。     

实施网络外语教学应注重的问题

实施网络外语教学应注重的几个问题 ,一是要认真考虑使用网络的教学目的 ,二是网络交流应该结合课程目的而展开 ,三是不能低估网络使用中存在的困难 ,四是在进行网络外语教学时教师必须提供必要的帮助 ,五是要让学生参与确定网络课堂教学的计划和内容     

非统计专业统计学教育刍议

针对非统计专业统计学教育目前存在的问题,阐述了提高对统计学重要性的认识是保证统计教学效果的前提;统计学教学环节的改革是提高教学效果的重要保证;统计教师的业务素质是提高统计教学效果的关键。     

Statistical Distributions of Daily Breathing Rates for Narrow Age Groups of Infants and Children

Children may be more susceptible to toxicity from some environmental chemicals than adults. This susceptibility may occur during narrow age periods (windows), which can last from days to years depending on the toxicant. Breathing rates specific to narrow age periods are useful to assess inhalation dose during suspected windows of susceptibility. Because existing breathing rates used in risk assessment are typically for broad age ranges or are based on data not representative of the population, we derived daily breathing rates for narrow age ranges of children designed to be more representative of the current U.S. children's population. These rates were derived using the metabolic conversion method of Layton (1993) and energy intake data adjusted to represent the U.S. population from a relatively recent dietary survey (CSFII 1994–1996, 1998). We calculated conversion factors more specific to children than those previously used. Both nonnormalized (L/day) and normalized (L/kg-day) breathing rates were derived and found comparable to rates derived using energy estimates that are accurate for the individuals sampled but not representative of the population. Estimates of breathing rate variability within a population can be used with stochastic techniques to characterize the range of risk in the population from inhalation exposures. For each age and age-gender group, we present the mean, standard error of the mean, percentiles (50th, 90th, and 95th), geometric mean, standard deviation, 95th percentile, and best-fit parametric models of the breathing rate distributions. The standard errors characterize uncertainty in the parameter estimate, while the percentiles describe the combined interindividual and intra-individual variability of the sampled population. These breathing rates can be used for risk assessment of subchronic and chronic inhalation exposures of narrow age groups of children.     

交流电路参数的实用测量法研究

探讨了二端交流电路的R,L,C元件参数的测定,并研究了工频电路的等效电阻、等效电抗的测量方法。