Outliers in incomplete multiresponse experiments

Identification of outlier vectors in block designs for incomplete multiresponse experiments has been considered. Design is composed of two sets of experimental units. Different numbers of response variables are observed from these two sets. Cook-statistic has been developed for identification of outliers. The developed statistic has been illustrated with a real-life data set. It has been shown that presence of outliers can distort the overall conclusion from an experiment.     

Pairwise comparisons of treatments with ordinal responses in a two-way setting

In clinical studies, pairwise comparisons are frequently performed to examine differences in efficacy between treatments. The statistical methods of pairwise comparisons are available when treatment responses are measured on an ordinal scale. The Wilcoxon–Mann–Whitney test and the latent normal model are popular examples. However, these procedures cannot be used to compare treatments in parallel groups (a two-way design) when overall type I error must be controlled. In this paper, we explore statistical approaches to the pairwise testing of treatments that satisfy the requirements of a two-way layout. The results of our simulation indicate that the latent normal approach is superior to the Wilcoxon–Mann–Whitney test. Clinical examples are used to illustrate our suggested testing methods.     

Extended scaled prediction variance optimality for modified central composite design

Robust parameter designs (RPDs) enable the experimenter to discover how to modify the design of the product to minimize the effect due to variation from noise sources. The aim of this article is to show how this amount of work can be reduced under modified central composite design (MCCD). We propose a measure of extended scaled prediction variance (ESPV) for evaluation of RPDs on MCCD. Using these measures, we show that we can check the error or bias associated with estimating the model parameters and suggest the values of α recommended for MCCS under minimum ESPV.     

Testing for bioequivalence of highly variable drugs from TR‐RT crossover designs with heterogeneous residual variances

Traditional bioavailability studies assess average bioequivalence (ABE) between the test (T) and reference (R) products under the crossover design with TR and RT sequences. With highly variable (HV) drugs whose intrasubject coefficient of variation in pharmacokinetic measures is 30% or greater, assertion of ABE becomes difficult due to the large sample sizes needed to achieve adequate power. In 2011, the FDA adopted a more relaxed, yet complex, ABE criterion and supplied a procedure to assess this criterion exclusively under TRR‐RTR‐RRT and TRTR‐RTRT designs. However, designs with more than 2 periods are not always feasible. This present work investigates how to evaluate HV drugs under TR‐RT designs. A mixed model with heterogeneous residual variances is used to fit data from TR‐RT designs. Under the assumption of zero subject‐by‐formulation interaction, this basic model is comparable to the FDA‐recommended model for TRR‐RTR‐RRT and TRTR‐RTRT designs, suggesting the conceptual plausibility of our approach. To overcome the distributional dependency among summary statistics of model parameters, we develop statistical tests via the generalized pivotal quantity (GPQ). A real‐world data example is given to illustrate the utility of the resulting procedures. Our simulation study identifies a GPQ‐based testing procedure that evaluates HV drugs under practical TR‐RT designs with desirable type I error rate and reasonable power. In comparison to the FDA's approach, this GPQ‐based procedure gives similar performance when the product's intersubject standard deviation is low (≤0.4) and is most useful when practical considerations restrict the crossover design to 2 periods.     

A simulation study of methods for selecting subgroup‐specific doses in phase 1 trials

Patient heterogeneity may complicate dose‐finding in phase 1 clinical trials if the dose‐toxicity curves differ between subgroups. Conducting separate trials within subgroups may lead to infeasibly small sample sizes in subgroups having low prevalence. Alternatively,it is not obvious how to conduct a single trial while accounting for heterogeneity. To address this problem,we consider a generalization of the continual reassessment method on the basis of a hierarchical Bayesian dose‐toxicity model that borrows strength between subgroups under the assumption that the subgroups are exchangeable. We evaluate a design using this model that includes subgroup‐specific dose selection and safety rules. A simulation study is presented that includes comparison of this method to 3 alternative approaches,on the basis of nonhierarchical models,that make different types of assumptions about within‐subgroup dose‐toxicity curves. The simulations show that the hierarchical model‐based method is recommended in settings where the dose‐toxicity curves are exchangeable between subgroups. We present practical guidelines for application and provide computer programs for trial simulation and conduct.     

Approximate confidence intervals for the weighted kappa coefficient of a binary diagnostic test subject to a case–control design

Case–control design to assess the accuracy of a binary diagnostic test (BDT) is very frequent in clinical practice. This design consists of applying the diagnostic test to all of the individuals in a sample of those who have the disease and in another sample of those who do not have the disease. The sensitivity of the diagnostic test is estimated from the case sample and the specificity is estimated from the control sample. Another parameter which is used to assess the performance of a BDT is the weighted kappa coefficient. The weighted kappa coefficient depends on the sensitivity and specificity of the diagnostic test, on the disease prevalence and on the weighting index. In this article, confidence intervals are studied for the weighted kappa coefficient subject to a case–control design and a method is proposed to calculate the sample sizes to estimate this parameter. The results obtained were applied to a real example.     

A closer look at de-aliasing effects using an efficient foldover technique

Foldover techniques are used to reduce the confounding when some important effects (usually lower order effects) cannot be estimated independently. This article develops an efficient foldover mechanism for symmetric or asymmetric designs, whether regular or nonregular. In this paper, we take the uniformity criteria (UC) as the optimality measures to construct the optimal combined designs (initial design plus its corresponding foldover design) which have better capability of estimating lower order effects. The relationship between any initial design and its combined design is studied. A comparison study between the combined designs via different UC is provided. Equivalence between any combined design and its complementary combined design is investigated, which is a very useful constraint that reduce the search space. Using our results as benchmarks, we can implement a powerful algorithm for constructing optimal combined designs. Our work covers as well as gives results better than recent works of about 20 articles in the last few years as special cases. So this article is a good reference for constructing effective designs.     

Attitude strength moderates adverse effects to questionnaire design

ABSTRACT

The presentation and visual design of the “don’t know” category in rating scales on respondents’ behavior may have ambivalent effects. The hypothesis is that attitude strength toward the topic influences the respondents’ sensitivity to the graphical design of the scale. A paper-and-pencil questionnaire conducted among 307 German university students contained an experimental variation of the presentation of a “don’t know” category and its visual design. A multinomial logistic regression shows that presenting a “don’t know” category drives respondents toward extreme categories. The visual design of the “don’t know” category influences the distribution of responses, all the more that the respondents’ attitudes toward the item topic are weak.     

基于SPOC平台的混合式教学新模式研究

SPOC混合式教学法是“互联网+”在教育领域的具体应用,是一种结合了线上教学和课堂教学的混合教学模式,是教学模式改革的一大突破。概述了SPOC混合式教学模式的内涵,分析了SPOC混合式教学法对教师教学及对学生学习效果的影响,并指出了SPOC混合式教学模式设计的四大环节。     

现代汉字设计字体的规范运用及其社会价值

汉字设计字体是现代经济社会高速发展的产物。从文字学角度看,汉字设计字体的出现不是偶然的．社会发展以及入本能的内在需求要求汉字创新求善,并且它的出现符合汉字自身的发展规律。这种设计字体与规范汉字从字形、字音、字义方面既有区别又有联系,以其独特的形式获得强烈的视觉感染力。它使信息传播差异化．有利于普及汉字知识教育和美育,同时具有创造和审美价值。这些潜在的社会价值为汉字设计字体进一步发展打下坚实基础。