Modifications of sequential designs in bioequivalence trials

Bioequivalence (BE) studies are designed to show that two formulations of one drug are equivalent and they play an important role in drug development. When in a design stage, it is possible that there is a high degree of uncertainty on variability of the formulations and the actual performance of the test versus reference formulation. Therefore, an interim look may be desirable to stop the study if there is no chance of claiming BE at the end (futility), or claim BE if evidence is sufficient (efficacy), or adjust the sample size. Sequential design approaches specially for BE studies have been proposed previously in publications. We applied modification to the existing methods focusing on simplified multiplicity adjustment and futility stopping. We name our method modified sequential design for BE studies (MSDBE). Simulation results demonstrate comparable performance between MSDBE and the original published methods while MSDBE offers more transparency and better applicability. The R package MSDBE is available at https://sites.google.com/site/modsdbe/ . Copyright © 2015 John Wiley & Sons, Ltd.     

A general inverse sampling scheme and its application to adaptive cluster sampling

Not having a variance estimator is a seriously weak point of a sampling design from a practical perspective. This paper provides unbiased variance estimators for several sampling designs based on inverse sampling, both with and without an adaptive component. It proposes a new design, which is called the general inverse sampling design, that avoids sampling an infeasibly large number of units. The paper provide estimators for this design as well as its adaptive modification. A simple artificial example is used to demonstrate the computations. The adaptive and non‐adaptive designs are compared using simulations based on real data sets. The results indicate that, for appropriate populations, the adaptive version can have a substantial variance reduction compared with the non‐adaptive version. Also, adaptive general inverse sampling with a limitation on the initial sample size has a greater variance reduction than without the limitation.     

宾位数量名结构中“一”字隐现的认知研究

宾语数量名结构中“一”字的省略必然引起人的认知心理上的变化。本文试从认知语言的角度,由距离像似动因及范畴化原型理论来分析宾语数量名结构中“一”字省略后引起的句法、语法、语用等变化问题。由此得出了“一”字省略后,整个结构数量意义减弱,语法性质不活泼,搭配受到了限制,缺乏独立性,语体风格发生了变化等结论。     

Sampling from spatial databases

This paper deals with techniques for obtaining random point samples from spatial databases. We seek random points from a continuous domain (usually ²) which satisfy a spatial predicate that is represented in the database as a collection of polygons. Several applications of spatial sampling (e.g. environmental monitoring, agronomy, forestry, etc) are described. Sampling problems are characterized in terms of two key parameters: coverage (selectivity), and expected stabbing number (overlap). We discuss two fundamental approaches to sampling with spatial predicates, depending on whether we sample first or evaluate the predicate first. The approaches are described in the context of both quadtrees and R-trees, detailing the sample first, acceptance/rejection tree, and partial area tree algorithms. A sequential algorithm, the one-pass spatial reservoir algorithm is also described. The relative performance of the various sampling algorithms is compared and choice of preferred algorithms is suggested. We conclude with a short discussion of possible extensions.     

非对称情况下的多物品拍卖

本文讨论当投标人之间存在不同的预算约束时两物品的序贯增价拍卖,对于物品之间不同的关系(互补、替代或者不相干的关系),物品价值大小的不同及与预算大小之间的关系,在一个简单的完全信息模型下,我们分不同情况讨论投标人的均衡出价策略,并发现对卖方来说,先拍卖价值高的物品是弱占优的策略。     

Robust block bootstrap panel predictability tests*

This article develops two block bootstrap-based panel predictability test procedures that are valid under very general conditions. Some of the allowable features include cross-sectional dependence, heterogeneous predictive slopes, persistent predictors, and complex error dynamics, including cross-unit endogeneity. While the first test procedure tests if there is any predictability at all, the second procedure determines the units for which predictability holds in case of a rejection by the first. A weak unit root framework is adopted to allow persistent predictors, and a novel theory is developed to establish asymptotic validity of the proposed bootstrap. Simulations are used to evaluate the performance of our tests in small samples, and their implementation is illustrated through an empirical application to stock returns.     

Sequential Hypothesis Tests for Identifying the Minimum Dose with a Threshold Effect

We propose a procedure to identify a lowest dose having greater effect than a threshold dose under the assumption of monotonicity of dose mean response in dose response test. So, we use statistics based on contrasts among sample means and apply a group sequential procedure to our procedure to identify effectively the dose. If we can identify the dose at an early step in the sequential test, since we can terminate the procedure with a few observations, the procedure is useful from an economical point of view. In a simulation studies, we compare the superiority among these procedures based on three contrasts.     

Does Iconicity in Pictographs Matter? The Influence of Iconicity and Numeracy on Information Processing,Decision Making,and Liking in an Eye‐Tracking Study

Researchers recommend the use of pictographs in medical risk communication to improve people's risk comprehension and decision making. However, it is not yet clear whether the iconicity used in pictographs to convey risk information influences individuals’ information processing and comprehension. In an eye‐tracking experiment with participants from the general population (N = 188), we examined whether specific types of pictograph icons influence the processing strategy viewers use to extract numerical information. In addition, we examined the effect of iconicity and numeracy on probability estimation, recall, and icon liking. This experiment used a 2 (iconicity: blocks vs. restroom icons) × 2 (scenario: medical vs. nonmedical) between‐subject design. Numeracy had a significant effect on information processing strategy, but we found no effect of iconicity or scenario. Results indicated that both icon types enabled high and low numerates to use their default way of processing and extracting the gist of the message from the pictorial risk communication format: high numerates counted icons, whereas low numerates used large‐area processing. There was no effect of iconicity in the probability estimation. However, people who saw restroom icons had a higher probability of correctly recalling the exact risk level. Iconicity had no effect on icon liking. Although the effects are small, our findings suggest that person‐like restroom icons in pictographs seem to have some advantages for risk communication. Specifically, in nonpersonalized prevention brochures, person‐like restroom icons may maintain reader motivation for processing the risk information.     

Multimodal representational gestures in the transition to multi-word productions

The aim of this study was to analyze the use of representational gestures from a multimodal point of view in the transition from one-word to multi-word constructions. Twenty-one Spanish-speaking children were observed longitudinally at 18, 21, 24, and 30 months of age. We analyzed the production of deictic, symbolic, and conventional gestures and their coordination with different verbal elements. Moreover, we explored the relationship between gestural multimodal and unimodal productions and independent measures of language development. Results showed that gesture production remains stable in the period studied. Whereas deictic gestures are frequent and mostly multimodal from the beginning, conventional gestures are rare and mainly unimodal. Symbolic gestures are initially unimodal, but between 24 and 30 months of age, this pattern reverses, with more multimodal symbolic gestures than unimodal. In addition, the frequency of multimodal representational gestures at specific ages seems to be positively related to independent measures of vocabulary and morphosyntax development. By contrast, the production of unimodal representational gestures appears negatively related to these measures. Our results suggest that multimodal representational gestures could have a facilitating role in the process of learning to combine meanings for communicative goals.     

Bayesian blinded sample size re-estimation

Information before unblinding regarding the success of confirmatory clinical trials is highly uncertain. Current techniques using point estimates of auxiliary parameters for estimating expected blinded sample size: (i) fail to describe the range of likely sample sizes obtained after the anticipated data are observed, and (ii) fail to adjust to the changing patient population. Sequential MCMC-based algorithms are implemented for purposes of sample size adjustments. The uncertainty arising from clinical trials is characterized by filtering later auxiliary parameters through their earlier counterparts and employing posterior distributions to estimate sample size and power. The use of approximate expected power estimates to determine the required additional sample size are closely related to techniques employing Simple Adjustments or the EM algorithm. By contrast with these, our proposed methodology provides intervals for the expected sample size using the posterior distribution of auxiliary parameters. Future decisions about additional subjects are better informed due to our ability to account for subject response heterogeneity over time. We apply the proposed methodologies to a depression trial. Our proposed blinded procedures should be considered for most studies due to ease of implementation.