The time‐dependent “cure‐death” model investigating two equally important endpoints simultaneously in trials treating high‐risk patients with resistant pathogens

A variety of primary endpoints are used in clinical trials treating patients with severe infectious diseases, and existing guidelines do not provide a consistent recommendation. We propose to study simultaneously two primary endpoints, cure and death, in a comprehensive multistate cure‐death model as starting point for a treatment comparison. This technique enables us to study the temporal dynamic of the patient‐relevant probability to be cured and alive. We describe and compare traditional and innovative methods suitable for a treatment comparison based on this model. Traditional analyses using risk differences focus on one prespecified timepoint only. A restricted logrank‐based test of treatment effect is sensitive to ordered categories of responses and integrates information on duration of response. The pseudo‐value regression provides a direct regression model for examination of treatment effect via difference in transition probabilities. Applied to a topical real data example and simulation scenarios, we demonstrate advantages and limitations and provide an insight into how these methods can handle different kinds of treatment imbalances. The cure‐death model provides a suitable framework to gain a better understanding of how a new treatment influences the time‐dynamic cure and death process. This might help the future planning of randomised clinical trials, sample size calculations, and data analyses.     

Interquantile shrinkage in additive models

In this paper, we investigate the commonality of nonparametric component functions among different quantile levels in additive regression models. We propose two fused adaptive group Least Absolute Shrinkage and Selection Operator penalties to shrink the difference of functions between neighbouring quantile levels. The proposed methodology is able to simultaneously estimate the nonparametric functions and identify the quantile regions where functions are unvarying, and thus is expected to perform better than standard additive quantile regression when there exists a region of quantile levels on which the functions are unvarying. Under some regularity conditions, the proposed penalised estimators can theoretically achieve the optimal rate of convergence and identify the true varying/unvarying regions consistently. Simulation studies and a real data application show that the proposed methods yield good numerical results.     

Estimation and inference of the joint conditional distribution for multivariate longitudinal data using nonparametric copulas

In this paper we study estimating the joint conditional distributions of multivariate longitudinal outcomes using regression models and copulas. For the estimation of marginal models, we consider a class of time-varying transformation models and combine the two marginal models using nonparametric empirical copulas. Our models and estimation method can be applied in many situations where the conditional mean-based models are not good enough. Empirical copulas combined with time-varying transformation models may allow quite flexible modelling for the joint conditional distributions for multivariate longitudinal data. We derive the asymptotic properties for the copula-based estimators of the joint conditional distribution functions. For illustration we apply our estimation method to an epidemiological study of childhood growth and blood pressure.     

Testing independence based on Bernstein empirical copula and copula density

In this paper we provide three nonparametric tests of independence between continuous random variables based on the Bernstein copula distribution function and the Bernstein copula density function. The first test is constructed based on a Cramér-von Mises divergence-type functional based on the empirical Bernstein copula process. The two other tests are based on the Bernstein copula density and use Cramér-von Mises and Kullback–Leibler divergence-type functionals, respectively. Furthermore, we study the asymptotic null distribution of each of these test statistics. Finally, we consider a Monte Carlo experiment to investigate the performance of our tests. In particular we examine their size and power which we compare with those of the classical nonparametric tests that are based on the empirical distribution function.     

Multiphase experiments in practice: A look back

Multiphase experiments are introduced and an overview of their design and analysis as it is currently practised is given via an account of their development since 1955 and a literature survey. Methods that are available for designing and analysing them are outlined, with an emphasis on making explicit the role of the model in their design. The availability of software and its use is described in detail. Overall, while multiphase designs have been applied in areas such as plant breeding, plant pathology, greenhouse experimentation, product storage, gene expression studies, and sensory evaluation, their deployment has been limited.     

Bayesian quantile regression for skew-normal linear mixed models

Linear mixed models have been widely used to analyze repeated measures data which arise in many studies. In most applications, it is assumed that both the random effects and the within-subjects errors are normally distributed. This can be extremely restrictive, obscuring important features of within-and among-subject variations. Here, quantile regression in the Bayesian framework for the linear mixed models is described to carry out the robust inferences. We also relax the normality assumption for the random effects by using a multivariate skew-normal distribution, which includes the normal ones as a special case and provides robust estimation in the linear mixed models. For posterior inference, we propose a Gibbs sampling algorithm based on a mixture representation of the asymmetric Laplace distribution and multivariate skew-normal distribution. The procedures are demonstrated by both simulated and real data examples.     

Modeling binary familial data using Gaussian copula

Modeling binary familial data has been a challenging task due to the dependence among family members and the constraints imposed on the joint probability distribution of the binary responses. This paper investigates some useful familial dependence structures and proposes analyzing binary familial data using Gaussian copula model. Advantages of this approach are discussed as well as some computational details. An numerical example is also presented with an aim to show the capability of Gaussian copula model in more sophisticated data analysis.     

Testing homogeneity in semiparametric mixture case–control models

Parametric and semiparametric mixture models have been widely used in applications from many areas, and it is often of interest to test the homogeneity in these models. However, hypothesis testing is non standard due to the fact that several regularity conditions do not hold under the null hypothesis. We consider a semiparametric mixture case–control model, in the sense that the density ratio of two distributions is assumed to be of an exponential form, while the baseline density is unspecified. This model was first considered by Qin and Liang (2011 Qin, J., Liang, K.Y. (2011). Hypothesis testing in a mixture case–control model. Biometrics 67(1):182–198.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar], biometrics), and they proposed a modified score statistic for testing homogeneity. In this article, we consider alternative testing procedures based on supremum statistics, which could improve power against certain types of alternatives. We demonstrate the connection and comparison among the proposed and existing approaches. In addition, we provide a unified theoretical justification of the supremum test and other existing test statistics from an empirical likelihood perspective. The finite-sample performance of the supremum test statistics was evaluated in simulation studies.     

潜在成长模型在体育运动领域的应用

介绍了潜在成长模型的发展、类型和内容,通过分析、归纳、整理等,比较了潜在成长模型与传统t检验、方差分析、回归分析的差别,探讨了潜在成长模型研究设计的要求,通过台湾棒球职业球员薪酬成长模型说明。利用文献调查法,分析了LGM潜在成长模型在体育运动领域中应用的概况,举例说明体育运动领域应用LGM的情况,证实了未来潜在成长模型会在体育科学领域逐渐受到重视并得到快速发展。