On False Discovery and Non‐discovery Proportions of the Dynamic Adaptive Procedure

This paper studies the asymptotic behaviour of the false discovery and non‐discovery proportions of the dynamic adaptive procedure under some dependence structure. A Bahadur‐type representation of the cut point in simultaneously performing a large scale of tests is presented. The asymptotic bias decompositions of the false discovery and non‐discovery proportions are given under some dependence structure. In addition to existing literatures, we find that the randomness due to the dynamic selection of the tuning parameter in estimating the true null rate serves as a source of the approximation error in the Bahadur representation and enters into the asymptotic bias term of the false discovery proportion and those of the false non‐discovery proportion. The theory explains to some extent why some seemingly attractive dynamic adaptive procedures do not outperform the competing fixed adaptive procedures substantially in some situations. Simulations justify our theory and findings.     

Flexible modelling of simultaneously interval censored and truncated time‐to‐event data

This paper deals with the analysis of data from a HET‐CAM^VT experiment. From a statistical perspective, such data yield many challenges. First of all, the data are typically time‐to‐event like data, which are at the same time interval censored and right truncated. In addition, one has to cope with overdispersion as well as clustering. Traditional analysis approaches ignore overdispersion and clustering and summarize the data into a continuous score that can be analysed using simple linear models. In this paper, a novel combined frailty model is developed that simultaneously captures all of the aforementioned statistical challenges posed by the data. Copyright © 2015 John Wiley & Sons, Ltd.     

A Bayesian estimate of the concordance correlation coefficient with skewed data

Concordance correlation coefficient (CCC) is one of the most popular scaled indices used to evaluate agreement. Most commonly, it is used under the assumption that data is normally distributed. This assumption, however, does not apply to skewed data sets. While methods for the estimation of the CCC of skewed data sets have been introduced and studied, the Bayesian approach and its comparison with the previous methods has been lacking. In this study, we propose a Bayesian method for the estimation of the CCC of skewed data sets and compare it with the best method previously investigated. The proposed method has certain advantages. It tends to outperform the best method studied before when the variation of the data is mainly from the random subject effect instead of error. Furthermore, it allows for greater flexibility in application by enabling incorporation of missing data, confounding covariates, and replications, which was not considered previously. The superiority of this new approach is demonstrated using simulation as well as real‐life biomarker data sets used in an electroencephalography clinical study. The implementation of the Bayesian method is accessible through the Comprehensive R Archive Network. Copyright © 2015 John Wiley & Sons, Ltd.     

Bayesian adaptive dose‐escalation procedures for binary and continuous responses utilizing a gain function

One of the main aims of early phase clinical trials is to identify a safe dose with an indication of therapeutic benefit to administer to subjects in further studies. Ideally therefore, dose‐limiting events (DLEs) and responses indicative of efficacy should be considered in the dose‐escalation procedure. Several methods have been suggested for incorporating both DLEs and efficacy responses in early phase dose‐escalation trials. In this paper, we describe and evaluate a Bayesian adaptive approach based on one binary response (occurrence of a DLE) and one continuous response (a measure of potential efficacy) per subject. A logistic regression and a linear log‐log relationship are used respectively to model the binary DLEs and the continuous efficacy responses. A gain function concerning both the DLEs and efficacy responses is used to determine the dose to administer to the next cohort of subjects. Stopping rules are proposed to enable efficient decision making. Simulation results shows that our approach performs better than taking account of DLE responses alone. To assess the robustness of the approach, scenarios where the efficacy responses of subjects are generated from an E _max model, but modelled by the linear log–log model are also considered. This evaluation shows that the simpler log–log model leads to robust recommendations even under this model showing that it is a useful approximation to the difficulty in estimating E _max model. Additionally, we find comparable performance to alternative approaches using efficacy and safety for dose‐finding. Copyright © 2015 John Wiley & Sons, Ltd.     

Hedging Barrier Options in GARCH Models with Transaction Costs

This study proposes a modified strike‐spread method for hedging barrier options in generalized autoregressive conditional heteroskedasticity (GARCH) models with transaction costs. A simulation study was conducted to investigate the hedging performance of the proposed method in comparison with several well‐known static methods for hedging barrier options. An accurate, easy‐to‐implement and fast scheme for generating the first passage time under the GARCH framework which enhances the accuracy and efficiency of the simulation is also proposed. Simulation results and an empirical study using real data indicate that the proposed approach has a promising performance for hedging barrier options in GARCH models when transaction costs are taken into consideration.     

Methods for exploring treatment effect heterogeneity in subgroup analysis: an application to global clinical trials

Multi‐country randomised clinical trials (MRCTs) are common in the medical literature, and their interpretation has been the subject of extensive recent discussion. In many MRCTs, an evaluation of treatment effect homogeneity across countries or regions is conducted. Subgroup analysis principles require a significant test of interaction in order to claim heterogeneity of treatment effect across subgroups, such as countries in an MRCT. As clinical trials are typically underpowered for tests of interaction, overly optimistic expectations of treatment effect homogeneity can lead researchers, regulators and other stakeholders to over‐interpret apparent differences between subgroups even when heterogeneity tests are insignificant. In this paper, we consider some exploratory analysis tools to address this issue. We present three measures derived using the theory of order statistics, which can be used to understand the magnitude and the nature of the variation in treatment effects that can arise merely as an artefact of chance. These measures are not intended to replace a formal test of interaction but instead provide non‐inferential visual aids, which allow comparison of the observed and expected differences between regions or other subgroups and are a useful supplement to a formal test of interaction. We discuss how our methodology differs from recently published methods addressing the same issue. A case study of our approach is presented using data from the Study of Platelet Inhibition and Patient Outcomes (PLATO), which was a large cardiovascular MRCT that has been the subject of controversy in the literature. An R package is available that implements the proposed methods. Copyright © 2014 John Wiley & Sons, Ltd.     

Threshold‐free estimation of functional antibody titers of a group B streptococcus opsonophagocytic killing assay

Opsonophagocytic killing assays (OPKA) are routinely used for the quantification of bactericidal antibodies in blood serum samples. Quantification of the OPKA readout, the titer, provides the basis for the statistical analysis of vaccine clinical trials having functional immune response endpoints. Traditional OPKA titers are defined as the maximum serum dilution yielding a predefined bacterial killing threshold value, and they are estimated by fitting a dose‐response model to the dilution‐killing curve. This paper illustrates a novel definition of titer, the threshold‐free titer, which preserves biological interpretability while not depending on any killing threshold or on a postulated shape of the dose‐response curve. These titers are shown to be more precise than the traditional threshold‐based titers when using simulated and experimental group B streptococcus OPKA experimental data. Also, titer linearity is shown to be not measurable when using threshold‐based titers, whereas it becomes measurable using threshold‐free titers. The biological interpretability and operational characteristics demonstrated here indicate that threshold‐free titers are an appropriate tool for the routine analysis of OPKA data. Copyright © 2015 John Wiley & Sons, Ltd.     

Maintaining and Strengthening a Shaky Regime with Mnemonic Work: Inventing a Chinese National Day from 1949 Through 1987 in Taiwan

This paper investigates the invention of a Chinese National Day from 1949 through 1987 in Taiwan to illuminate the significance of mnemonic work in nation‐building. The 1949 Retreat after the Chinese Civil War resulted in a serious legitimacy crisis for the government of the Republic of China; thus, (re)inventing the National Day became an important mission to maintain and even strengthen this shaky regime. While the role of the standardized commemorative narrative in influencing people's collective memory is granted, this article emphasizes the aspect of embodied memory in nation‐remembering. I point out that the official Chinese nationalism constructed its National Day as “inevitably” bustling, memorialized, accepted, heroic, familial‐ized, blessed, and pivotal‐ized to shape the impression of a sacred and memorable day. This paper—while essentially consistent with Billig's argument of banal nationalism—suggests that national identity is accumulated by many symbolically encoded elements found in daily life; it goes further to argue that banal nationalism needs the “hot” nationalism found in special occasions to encode, refresh, and redefine the symbolic meaning of entities. That is, the oscillations between sacred and profane are needed to guarantee that patriotic emotions can be continually created and maintained.