A pragmatic dose‐finding approach using short‐term surrogate efficacy outcomes to evaluate binary efficacy and toxicity outcomes in phase I cancer clinical trials

There is a growing need for study designs that can evaluate efficacy and toxicity outcomes simultaneously in phase I or phase I/II cancer clinical trials. Many dose‐finding approaches have been proposed; however, most of these approaches assume binary efficacy and toxicity outcomes, such as dose‐limiting toxicity (DLT), and objective responses. DLTs are often defined for short time periods. In contrast, objective responses are often defined for longer periods because of practical limitations on confirmation and the criteria used to define ‘confirmation’. This means that studies have to be carried out for unacceptably long periods of time. Previous studies have not proposed a satisfactory solution to this specific problem. Furthermore, this problem may be a barrier for practitioners who want to implement notable previous dose‐finding approaches. To cope with this problem, we propose an approach using unconfirmed early responses as the surrogate efficacy outcome for the confirmed outcome. Because it is reasonable to expect moderate positive correlation between the two outcomes and the method replaces the surrogate outcome with the confirmed outcome once it becomes available, the proposed approach can reduce irrelevant dose selection and accumulation of bias. Moreover, it is also expected that it can significantly shorten study duration. Using simulation studies, we demonstrate the positive utility of the proposed approach and provide three variations of it, all of which can be easily implemented with modified likelihood functions and outcome variable definitions. Copyright © 2013 John Wiley & Sons, Ltd.     

Incorporating historical controls using a random-effects model with a normal prior

Employing a variance stabilization transformation, a random-effects model with a normal prior is proposed for incorporating historical controls in the estimation of dose-response relationships. The advantages and disadvantages of maximum likelihood and empirical Bayes estimators are discussed. A two-stage method is introduced for the prudent use of historical controls.     

Conditional Inclusion: Sexual Minorities,Tolerance, and Nationalism

This article discusses how the approach towards sexual minorities has shifted from exclusion to inclusion between the mid-1980s and the present, and explores how the view that Japan is more tolerant of sexual minorities than the USA and Europe actually limits discussions on citizenship. An examination of the AIDS crisis and the Fuchu Youth Center court case in the 1980s and 1990s shows that gay men were regarded as a threat to national identity, seen to endanger Japan and whose sexuality was deemed to be unintelligible. In a word, their citizenship was denied. In the 2010s the ruling Liberal Democratic party issued a report on sexual orientation and gender identity (SOGI) issues, which examined measures aimed at achieving equality for those who suffer from SOGI discrimination. While sexual minorities became an object of inclusion, only partial and circumscribed citizenship was granted. Although the report ostensibly aims to promote SOGI diversity, it relegates the existence of minorities to the private sphere, and limits diversity by demanding the acceptance of a “tolerant culture” predicated on heterosexism and gender norms. By positioning their diversity effort in Japan's “tolerant traditional culture,” the party inadvertently incorporates nationalism and renders it central to their approach towards SOGI diversity. This article concludes that the discourse that the Japanese state is tolerant of sexual minorities undermines the recognition of sexual minorities’ citizenship.     

Context dependence and consistency in dynamic choice under uncertainty: the case of anticipated regret

We examine if and to what extent choice dispositions can allow dependence on contexts and maintain consistency over time, in a dynamic environment under uncertainty. We focus on one of the context dependence properties, opportunity dependence because of being affected by anticipated regret, where the consequentialist choice framework is maintained. There are two sources of potential inconsistency: one is arrival of information, and the other is changing opportunities. First, we go over the general method of resolution of potential inconsistency, by taking any kinds of inconsistency as given constraints. Second, we characterize a class of choice dispositions that are consistent to information arrival, but may be inconsistent to changing opportunities. Finally, we consider the overall requirement of dynamic consistency and show that it necessarily implies each of consistency to information arrival and independence of choice opportunities. The last result states that the two kinds of potential inconsistency cannot “compensate” each other to recover dynamic consistency overall.     

On the distributions of multivariate sample skewness

In this paper, we consider the multivariate normality test based on measure of multivariate sample skewness defined by Srivastava (1984). Srivastava derived asymptotic expectation up to the order N⁻¹ for the multivariate sample skewness and approximate χ²${\chi }^2$ test statistic, where N   is sample size. Under normality, we derive another expectation and variance for Srivastava's multivariate sample skewness in order to obtain a better test statistic. From this result, improved approximate χ²${\chi }^2$ test statistic using the multivariate sample skewness is also given for assessing multivariate normality. Finally, the numerical result by Monte Carlo simulation is shown in order to evaluate accuracy of the obtained expectation, variance and improved approximate χ²${\chi }^2$ test statistic. Furthermore, upper and lower percentiles of χ²${\chi }^2$ test statistic derived in this paper are compared with those of χ²${\chi }^2$ test statistic derived by Mardia (1974) which is used multivariate sample skewness defined by Mardia (1970).     

Cross-Cultural Psychology in Japan

This article portrays the situation of cross-cultural psychology in Japan, including historical background, institutional aspects, and research findings by Japanese investigators. Reflecting the internationalization of Japanese society, cultural influences on human behavior have recently drawn the attention of Japanese psychologists, and the number of researchers engaged in cross-cultural investigations is steadily increasing. A review of articles in current Japanese journals suggests that most cross-cultural studies belong to the areas of social, educational, and developmental psychology where they increasingly focus on specific themes and hypotheses. Although cross-cultural psychologists interact in each research area, cross-cultural findings have only rarely been discussed or integrated on the common plane of cross-cultural psychology. In part, this is true because no association of cross-cultural psychology exists in Japan. The authors emphasize the importance of a systematic approach to response styles which influence research findings and the fruitfulness of comparing Japanese findings to those obtained in other non-Western societies.     

A study on the relationship between commitment of club activity and vocational readiness among university students

The purpose of this study was to clarify the relationship between commitment of club activities and the vocational readiness among juniors at university. In this study, organizational commitment questionnaire (Mowday, 1979) and vocational readiness scale (Wakabayashi, Goto, and Shinkai, 1983) were tested with 178 (120 men, 58 women) juniors at one physical education university in the metropolitan area. According to correlation analysis, the relation between commitment of club activities and the vocational readiness was positive significant correlation (r = .303, p < .01). Moreover, we executed t-test. As the combined results, this study provided the following three conclusions; 1) Vocational readiness score of students who belonged to the club were higher than that of other students. 2) Vocational readiness score of students who were committed to club activities were higher than that of students with low commitment to club activities. 3) Students who were committed to club activities tended to increase the score of vocational readiness. It was not able to be declared that there were positive influences of the club activities in university education from the viewpoint of vocational readiness acquisition. Therefore, it is necessary to consider what the club activities should be from the viewpoint of university student's career education.     

Avowed Happiness in Confucian Asia: Ascertaining its Distribution,Patterns, and Sources

This study reviewed three philosophical accounts of happiness, and then tested those accounts with the Asiabarometer surveys conducted in six Confucian societies during the summer of 2006. Statistical analyses of these surveys reveal that East Asians tend to experience happiness to a greater extent when they experience enjoyment together with achievement and/or satisfaction. The preponderance of such multi-dimensional conceptions in all those societies poses a direct challenge to a single dimensional account of happiness in the West. The analyses also reveal that positive assessments of interpersonal relationships matter more than the amount of knowledge or wealth in living a happy life in Confucian societies.

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A simple test for the treatment effect in clinical trials with a sequential parallel comparison design and negative binomial outcomes

In placebo‐controlled, double‐blinded, randomized clinical trials, the presence of placebo responders reduces the effect size for comparison of the active drug group with the placebo group. An attempt to resolve this problem is to use the sequential parallel comparison design (SPCD). Although there are SPCDs with dichotomous or continuous outcomes, an SPCD with negative binomial outcomes—with which investigators deal eg, in clinical trials involving multiple sclerosis, where the investigators are still concerned about the presence of placebo responders—has not yet been discussed. In this article, we propose a simple test for the treatment effect in clinical trials with an SPCD and negative binomial outcomes. Through simulations, we show that the analysis method achieves the nominal type I error rate and power, whereas the sample size calculation provides the sample size with adequate power accuracy.     

Small grid drawings of planar graphs with balanced partition

In a grid drawing of a planar graph, every vertex is located at a grid point, and every edge is drawn as a straight-line segment without any edge-intersection. It is known that every planar graph G of n vertices has a grid drawing on an (n?2)×(n?2) or (4n/3)×(2n/3) integer grid. In this paper we show that if a planar graph G has a balanced partition then G has a grid drawing with small grid area. More precisely, if a separation pair bipartitions G into two edge-disjoint subgraphs G ₁ and?G ₂, then G has a max?{n ₁,n ₂}×max?{n ₁,n ₂} grid drawing, where n ₁ and n ₂ are the numbers of vertices in G ₁ and?G ₂, respectively. In particular, we show that every series-parallel graph G has a (2n/3)×(2n/3) grid drawing and a grid drawing with area smaller than 0.3941n ² (<(2/3)² n ²).