Likelihood approach for evaluating bioequivalence of highly variable drugs

Bioequivalence (BE) is required for approving a generic drug. The two one‐sided tests procedure (TOST, or the 90% confidence interval approach) has been used as the mainstream methodology to test average BE (ABE) on pharmacokinetic parameters such as the area under the blood concentration‐time curve and the peak concentration. However, for highly variable drugs (%CV > 30%), it is difficult to demonstrate ABE in a standard cross‐over study with the typical number of subjects using the TOST because of lack of power. Recently, the US Food and Drug Administration and the European Medicines Agency recommended similar but not identical reference‐scaled average BE (RSABE) approaches to address this issue. Although the power is improved, the new approaches may not guarantee a high level of confidence for the true difference between two drugs at the ABE boundaries. It is also difficult for these approaches to address the issues of population BE (PBE) and individual BE (IBE). We advocate the use of a likelihood approach for representing and interpreting BE data as evidence. Using example data from a full replicate 2 × 4 cross‐over study, we demonstrate how to present evidence using the profile likelihoods for the mean difference and standard deviation ratios of the two drugs for the pharmacokinetic parameters. With this approach, we present evidence for PBE and IBE as well as ABE within a unified framework. Our simulations show that the operating characteristics of the proposed likelihood approach are comparable with the RSABE approaches when the same criteria are applied. Copyright © 2014 John Wiley & Sons, Ltd.     

杂合灰色聚类与变精度粗糙模糊集的概率决策方法及应用

在基于粗糙集理论或扩展粗糙集理论的不确定性决策中,仅由数据集无法获得决策表,同时由于决策属性呈现模糊性,以致于难以获取概率决策规则。针对这一类决策问题,基于灰色定权聚类与优势粗糙集变精度方法,本文构建了一种的杂合决策方法。该方法首先利用中心点三角白化权函数的灰色定权聚类方法将包含不同量纲指标的知识表示系统生成多属性决策表,而后运用变精度粗糙模糊集进行决策分析,生成概率决策规则,最后以区域关键技术的选择为例,表明该模型的可行性与实用性。     

Distribution lot-sizing models for arborescent supply chains with discrete-period variable demand

This study formulates a novel mixed-integer programming lot-sizing model for arborescent supply chains with discrete-period variable demand and then develops an efficient two-phase heuristic method, in which a combined multi-period demand ordering policy, rather than the lot-for-lot ordering policy usually assumed in previous papers, is adopted. Two important properties are introduced and used to obtain a better initial feasible solution. The good performance of the proposed heuristic method is verified through a comparison with the optimal solution method. It is also shown that the performance of the proposed combined multi-period demand ordering method is superior to that of the lot-for-lot ordering method. Sensitivity analysis is conducted to explore the impacts of changing the values of relevant parameters on the total supply chain cost, the total number of orders and the total number of opened members. Finally, a well-known logistics company in Taiwan is chosen to demonstrate the excellent performance and the aptness of the proposed ordering method.     

Universal equation for the relative change in profit of manufacturing company

In contemporary conditions of the company's business operations, where high dynamics of costs, sales volume and change of production programme is present, it is of crucial importance to investigate their effects on the change of profit. Starting from cost–volume–profit equation, the aim is to arrive at a universal equation that will simultaneously measure a relative change in profit for a number of products, not only under the influence of change in sales volume but also of other relevant variables, such as sales price, fixed and variable costs. The basic hypothesis is that it is possible to establish in a form of universal equation the dependence between the change in profit and change in influential variables. In this investigation, first it was observed the partial influence of some variables on the change in profit and their dependence was determined for a single product, and then for more than one product. Finally, by summing up all those effects, a universal equation of profit change was obtained. The derived universal equation for the relative change in profit along with simultaneous effects of several variables makes possible for the company management to more simply determine the profit for diverse conditions of business operations. The universal equation for the relative change in profit was applied in one company and the results obtained confirm its significance.     

基于零膨胀分位数两部模型的银行贷款违约预测研究

贷款信用风险评估是银行风控的重要内容。贷款逾期天数作为常见的风险度量指标,具有典型的零膨胀特征。对于零膨胀数据,传统的线性回归不再适用,两部模型是常用的代表方法。考虑到贷款数据具有偏态分布特征,本文构建了一个分位数两部模型—logit-quantile模型。该模型由Logistic回归和分位数回归构成,为了进行风险因素的选择,在模型的两个回归中添加了Lasso惩罚。为了求解模型,本文采用了坐标下降法和线性规划法相结合的迭代算法。模拟分析显示,对比逐步法和常用的logit-linear两部模型,新模型表现出了最好的变量选择效果,尤其在零膨胀比例为80%及高维情形时,该模型的表现仍然最优。最后对某银行的贷款数据实证分析显示,新模型具有更精简的结构,采用交叉验证技术进行预测显示新模型的预测和分类表现最好。     

电子市场中时间价格敏感需求下的交货期定价决策

电子市场中,如何通过交货期报价来增大需求、提高收益,对于网络营销企业来说是至关重要的.本文假定在一个包含网络营销企业与其客户的运作系统中,需求同时对价格与时间都敏感的条件下,以最优化自身收益为目标、以满足必须达到规定的服务水平为主要约束条件,构建了交货期定价决策模型.通过数值算例,探讨了在电子市场中消费者为价格敏感或交货期敏感时,网络营销企业的最优定价策略.上述结论可以为网络营销企业在电子市场中的定价决策提供有益的指导.     

Sampling design proportional to order statistic of auxiliary variable

The sampling designs dependent on sample moments of auxiliary variables are well known. Lahiri (Bull Int Stat Inst 33:133–140, 1951) considered a sampling design proportionate to a sample mean of an auxiliary variable. Sing and Srivastava (Biometrika 67(1):205–209, 1980) proposed the sampling design proportionate to a sample variance while Wywiał (J Indian Stat Assoc 37:73–87, 1999) a sampling design proportionate to a sample generalized variance of auxiliary variables. Some other sampling designs dependent on moments of an auxiliary variable were considered e.g. in Wywiał (Some contributions to multivariate methods in, survey sampling. Katowice University of Economics, Katowice, 2003a); Stat Transit 4(5):779–798, 2000) where accuracy of some sampling strategies were compared, too.These sampling designs cannot be useful in the case when there are some censored observations of the auxiliary variable. Moreover, they can be much too sensitive to outliers observations. In these cases the sampling design proportionate to the order statistic of an auxiliary variable can be more useful. That is why such an unequal probability sampling design is proposed here. Its particular cases as well as its conditional version are considered, too. The sampling scheme implementing this sampling design is proposed. The inclusion probabilities of the first and second orders were evaluated. The well known Horvitz–Thompson estimator is taken into account. A ratio estimator dependent on an order statistic is constructed. It is similar to the well known ratio estimator based on the population and sample means. Moreover, it is an unbiased estimator of the population mean when the sample is drawn according to the proposed sampling design dependent on the appropriate order statistic.     

水性感光胶的理论探讨及发展

本文回顾了水性感光胶的科研开发过程，从设计思路，主要组成及影响感光质量的若干因素等方面作了讨论，重点介绍了重氮盐体系。     

Bayesian semiparametric inference for the accelerated failure-time model

Bayesian semiparametric inference is considered for a loglinear model. This model consists of a parametric component for the regression coefficients and a nonparametric component for the unknown error distribution. Bayesian analysis is studied for the case of a parametric prior on the regression coefficients and a mixture-of-Dirichlet-processes prior on the unknown error distribution. A Markov-chain Monte Carlo (MCMC) method is developed to compute the features of the posterior distribution. A model selection method for obtaining a more parsimonious set of predictors is studied. The method adds indicator variables to the regression equation. The set of indicator variables represents all the possible subsets to be considered. A MCMC method is developed to search stochastically for the best subset. These procedures are applied to two examples, one with censored data.     

Variable selection in partial linear regression with functional covariate

The problem of variable selection is considered in high-dimensional partial linear regression under some model allowing for possibly functional variable. The procedure studied is that of nonconcave-penalized least squares. It is shown the existence of a √n/s_n-consistent estimator for the vector of p_n linear parameters in the model, even when p_n tends to ∞ as the sample size n increases (s_n denotes the number of influential variables). An oracle property is also obtained for the variable selection method, and the nonparametric rate of convergence is stated for the estimator of the nonlinear functional component of the model. Finally, a simulation study illustrates the finite sample size performance of our procedure.