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.     

立足高起点发展新方向培养应用型复合型人才——对我院法学专业教学的认识及建议

我院法学专业培养目标是为社会培养应用型、复合型人才 ,针对实际情况 ,作者提出应改革教学内容 ,优化课程体系 ;改革教学方法 ,完善教学手段 ;提高教师业务水平 ,加强学术梯队建设等建议。     

孔子的富贵观及其现代价值解读

孔子的富贵观是其思想体系的重要组成部分。孔子关于世人应否追求富贵,怎样处理富贵与道义的关系,以及富裕之后还当如何等问题在《论语》中都有论述。孔子的这些论述,对当代人们创业致富,以义求利,以及坚持经济建设与精神文明建设两手抓,仍然具有启迪作用和借鉴价值。     

论审美理念系统的价值阶位

审美理念系统,以其特有的知识形式反映着人类审美价值的阶位需求。文中论述了人类最有代表性的五种阶位需求,认为虽然它们都反映一定的审美本质,但从生命与价值超越角度考虑,它们的内在思想特色和精神追求,还存在着很大的区别。     

日、唐律令官人出身制度的比较研究

通过日、唐律令官人出身制度的分析比较可以看出,古代日本的贡举(科举)实际上是作为荫位制的一种附属形式而存在,从这个侧面可以发现日、唐政体的异同,探究古代日本政治体制的发展进程。     

足球运动员的智力训练

智力训练是足球训练重要的一部份。本文揭示了运动员智力构成的因素,指明了足球运动员智力训练的意义,内容与方法。     

Uncertainty Analysis for Computer Model Projections of Hurricane Losses

Projecting losses associated with hurricanes is a complex and difficult undertaking that is wrought with uncertainties. Hurricane Charley, which struck southwest Florida on August 13, 2004, illustrates the uncertainty of forecasting damages from these storms. Due to shifts in the track and the rapid intensification of the storm, real-time estimates grew from 2 to 3 billion dollars in losses late on August 12 to a peak of 50 billion dollars for a brief time as the storm appeared to be headed for the Tampa Bay area. The storm hit the resort areas of Charlotte Harbor near Punta Gorda and then went on to Orlando in the central part of the state, with early poststorm estimates converging on a damage estimate in the 28 to 31 billion dollars range. Comparable damage to central Florida had not been seen since Hurricane Donna in 1960. The Florida Commission on Hurricane Loss Projection Methodology (FCHLPM) has recognized the role of computer models in projecting losses from hurricanes. The FCHLPM established a professional team to perform onsite (confidential) audits of computer models developed by several different companies in the United States that seek to have their models approved for use in insurance rate filings in Florida. The team's members represent the fields of actuarial science, computer science, meteorology, statistics, and wind and structural engineering. An important part of the auditing process requires uncertainty and sensitivity analyses to be performed with the applicant's proprietary model. To influence future such analyses, an uncertainty and sensitivity analysis has been completed for loss projections arising from use of a Holland B parameter hurricane wind field model. Uncertainty analysis quantifies the expected percentage reduction in the uncertainty of wind speed and loss that is attributable to each of the input variables.     

基于层次分析法与模糊评价的学科水平评估

在学科建设中,学科水平评估可以采用专家咨询的方法,分别从学术队伍、科学研究、教学与人才培养和工作条件四个方面设计学科水平评估指标体系,运用层次分析法确定指标权重系数,针对评估指标的模糊性,建立学科水平评估模糊综合评价模型,并通过实例分析和计算,证明该学科水平评估体系合理、有效、可行。     

Uniform asymptotic linearity of a process based on a signed rank statistic

Consider the process with, cf. (1.2) on page 265 in B1, X₁, …, X_N a sample from a distribution F and, for i = 1, …, N, R${}_{\text{|x}{}_{\text{1}}\text{, - q}{}_{\text{1}}\text{ø|}}$ , the rank of |X₁ - q₁ø| among |X₁ - q₁ø|, …, |X_N - q_Nø|. It is shown that, under certain regularity conditions on F and on the constants p_i and q_i, T^ø_N(t) is asymptotically approximately a linear function of ø uniformly in t and in ø for |ø| ≤ C. The special case where the p_i and the q_i, are independent of i is considered.     

Nonparametric analysis of treatment effects with missing observations

This paper develops a test for comparing treatment effects when observations are missing at random for repeated measures data on independent subjects. It is assumed that missingness at any occasion follows a Bernoulli distribution. It is shown that the distribution of the vector of linear rank statistics depends on the unknown parameters of the probability law that governs missingness, which is absent in the existing conditional methods employing rank statistics. This dependence is through the variance–covariance matrix of the vector of linear ranks. The test statistic is a quadratic form in the linear rank statistics when the variance–covariance matrix is estimated. The limiting distribution of the test statistic is derived under the null hypothesis. Several methods of estimating the unknown components of the variance–covariance matrix are considered. The estimate that produces stable empirical Type I error rate while maintaining the highest power among the competing tests is recommended for implementation in practice. Simulation studies are also presented to show the advantage of the proposed test over other rank-based tests that do not account for the randomness in the missing data pattern. Our method is shown to have the highest power while also maintaining near-nominal Type I error rates. Our results clearly illustrate that even for an ignorable missingness mechanism, the randomness in the pattern of missingness cannot be ignored. A real data example is presented to highlight the effectiveness of the proposed method.