Some group sequential procedures for comparing several treatments with a control

The purpose of this paper is to provide some group sequential procedures for comparing several treatments with a control. These procedures are the generalizations to the sequential sampling setting of the single-step procedure of Dunnett and the step-down procedure of Hochberg and Tamhane. When the responses are independent normal random variables with a common known variance, the critical values for specified alpha-levels are tabulated. The situation where the responses are binary random variables is also discussed.     

A Simulation Study of the Performance of Five Discriminant Analysis Methods for Mixtures of Continuous and Binary Variables

The present study investigates the performance of fice discrimination methods for data consisting of a mixture of continuous and binary variables. The methods are Fisher’s linear discrimination, logistic discrimination, quadratic discrimination, a kernal model and an independence model. Six-dimensional data, consisting of three binary and three continuous variables, are simulated according to a location model. The results show an almost identical performance for Fisher’s linear discrimination and logistic discrimination. Only in situations with independently distributed variables the independence model does have a reasonable discriminatory ability for the dimensionality considered. If the log likelihood ratio is non-linear ratio is non-linear with respect to its continuous and binary part, the quadratic discrimination method is substantial better than linear and logistic discrimination, followed by the kernel method. A very good performance is obtained when in every situation the better one of linear and quardratic discrimination is used.     

The Multivariate Randomized Complete Block Design: A Novel Permutation Solution in Case of Ordered Categorical Variables

In this article, multivariate extensions of the combination-based test statistics for the comparison of several treatments in the multivariate Randomized Complete Block designs are introduced in case of categorical response variables. Several tests for the multivariate Randomized Complete Block designs, including MANOVA procedure, are compared with the method proposed via a Monte Carlo simulation study. The method has also been applied to a real case study in the field of sensorial testing studies. Results suggest that in each experimental situation where normality of the supposed underlying continuous model is hard to justify and especially when errors have heavy-tailed distributions, the proposed nonparametric procedure can be considered as a valid solution.     

Bayesian decision procedures for binary and continuous bivariate dose-escalation studies

In this paper, Bayesian decision procedures are developed for dose-escalation studies based on binary measures of undesirable events and continuous measures of therapeutic benefit. The methods generalize earlier approaches where undesirable events and therapeutic benefit are both binary. A logistic regression model is used to model the binary responses, while a linear regression model is used to model the continuous responses. Prior distributions for the unknown model parameters are suggested. A gain function is discussed and an optional safety constraint is included.     

Pseudo latent models: Goodness of fit measures, residuals, estimation, testing, and simulation

Binary response models consider pseudo-R ² measures which are not based on residuals while several concepts of residuals were developed for tests. In this paper the endogenous variable of the latent model corresponding to the binary observable model is substituted by a pseudo variable. Then goodness of fit measures and tests can be based on a joint concept of residuals as for linear models. Different kinds of residuals based on probit ML estimates are employed. The analytical investigations and the simulation results lead to the recommendation to use standardized residuals where there is no difference between observed and generalized residuals. In none of the investigated situations this estimator is far away from the best result. While in large samples all considered estimators are very similar, small sample properties speak in favour of residuals which are modifications of those suggested in the literature. An empirical application demonstrates that it is not necessary to develop new testing procedures for the observable models with dichotomous regressands. Well-know approaches for linear models with continuous endogenous variables which are implemented in usual econometric packages can be used for pseudo latent models. An erratum to this article is available at .     

A response-adaptive design in crossover trial

In the present work, whenever the response variables are binary, we frame an adaptive allocation rule for a two-treatment two-period crossover design in the presence of possible carry-over effects. The proposed rule is a combination of the play-the-winner and randomized play-the-winner rules. We study various properties of the proposed rule through asymptotics and simulations. Some related inferential problems are also considered. The proposed procedure is compared with some possible competitor.     

ON SELECTING VARIABLES AND ASSESSING THEIR PERFORMANCE IN LINEAR DISCRIMINANT ANALYSIS

Linear discriminant analysis between two populations is considered in this paper. Error rate is reviewed as a criterion for selection of variables, and a stepwise procedure is outlined that selects variables on the basis of empirical estimates of error. Problems with assessment of the selected variables are highlighted. A leave-one-out method is proposed for estimating the true error rate of the selected variables, or alternatively of the selection procedure itself. Monte Carlo simulations, of multivariate binary as well as multivariate normal data, demonstrate the feasibility of the proposed method and indicate its much greater accuracy relative to that of other available methods.     

A mixture latent variable model for modeling mixed data in heterogeneous populations and its applications

Latent variable models are widely used for jointly modeling of mixed data including nominal, ordinal, count and continuous data. In this paper, we consider a latent variable model for jointly modeling relationships between mixed binary, count and continuous variables with some observed covariates. We assume that, given a latent variable, mixed variables of interest are independent and count and continuous variables have Poisson distribution and normal distribution, respectively. As such data may be extracted from different subpopulations, consideration of an unobserved heterogeneity has to be taken into account. A mixture distribution is considered (for the distribution of the latent variable) which accounts the heterogeneity. The generalized EM algorithm which uses the Newton–Raphson algorithm inside the EM algorithm is used to compute the maximum likelihood estimates of parameters. The standard errors of the maximum likelihood estimates are computed by using the supplemented EM algorithm. Analysis of the primary biliary cirrhosis data is presented as an application of the proposed model.     

Non-parametric smoothing of the location model in mixed variable discrimination

The location model is a familiar basis for discriminant analysis of mixtures of categorical and continuous variables. Its usual implementation involves second-order smoothing, using multivariate regression for the continuous variables and log-linear models for the categorical variables. In spite of the smoothing, these procedures still require many parameters to be estimated and this in turn restricts the categorical variables to a small number if implementation is to be feasible. In this paper we propose non-parametric smoothing procedures for both parts of the model. The number of parameters to be estimated is dramatically reduced and the range of applicability thereby greatly increased. The methods are illustrated on several data sets, and the performances are compared with a range of other popular discrimination techniques. The proposed method compares very favourably with all its competitors.     

On a class of partially sequential two-sample test procedures for multivariate continuous data

In a two-sample testing problem, sometimes one of the sample observations are difficult and/or costlier to collect compared to the other one. Also, it may be the situation that sample observations from one of the populations have been previously collected and for operational advantages we do not wish to collect any more observations from the second population that are necessary for reaching a decision. Partially sequential technique is found to be very useful in such situations. The technique gained its popularity in statistics literature due to its very nature of capitalizing the best aspects of both fixed and sequential procedures. The literature is enriched with various types of partially sequential techniques useable under different types of data set-up. Nonetheless, there is no mention of multivariate data framework in this context, although very common in practice. The present paper aims at developing a class of partially sequential nonparametric test procedures for two-sample multivariate continuous data. For this we suggest a suitable stopping rule adopting inverse sampling technique and propose a class of test statistics based on the samples drawn using the suggested sampling scheme. Various asymptotic properties of the proposed tests are explored. An extensive simulation study is also performed to study the asymptotic performance of the tests. Finally the benefit of the proposed test procedure is demonstrated with an application to a real-life data on liver disease.     

Practical Advice on How to Impute Continuous Data When the Ultimate Interest Centers on Dichotomized Outcomes Through Pre-Specified Thresholds

Multiple imputation under the multivariate normality assumption has often been regarded as a viable model-based approach in dealing with incomplete continuous data in the last two decades. A situation where the measurements are taken on a continuous scale with an ultimate interest in dichotomized versions through discipline-specific thresholds is not uncommon in applied research, especially in medical and social sciences. In practice, researchers generally tend to impute missing values for continuous outcomes under a Gaussian imputation model, and then dichotomize them via commonly-accepted cut-off points. An alternative strategy is creating multiply imputed data sets after dichotomization under a log-linear imputation model that uses a saturated multinomial structure. In this work, the performances of the two imputation methods were examined on a fairly wide range of simulated incomplete data sets that exhibit varying distributional characteristics such as skewness and multimodality. Behavior of efficiency and accuracy measures was explored to determine the extent to which the procedures work properly. The conclusion drawn is that dichotomization before carrying out a log-linear imputation should be the preferred approach except for a few special cases. I recommend that researchers use the atypical second strategy whenever the interest centers on binary quantities that are obtained through underlying continuous measurements. A possible explanation is that erratic/idiosyncratic aspects that are not accommodated by a Gaussian model are probably transformed into better-behaving discrete trends in this particular missing-data setting. This premise outweighs the assertion that continuous variables inherently carry more information, leading to a counter-intuitive, but potentially useful result for practitioners.     

Using the Standardized Difference to Compare the Prevalence of a Binary Variable Between Two Groups in Observational Research

Researchers are increasingly using the standardized difference to compare the distribution of baseline covariates between treatment groups in observational studies. Standardized differences were initially developed in the context of comparing the mean of continuous variables between two groups. However, in medical research, many baseline covariates are dichotomous. In this article, we explore the utility and interpretation of the standardized difference for comparing the prevalence of dichotomous variables between two groups. We examined the relationship between the standardized difference, and the maximal difference in the prevalence of the binary variable between two groups, the relative risk relating the prevalence of the binary variable in one group compared to the prevalence in the other group, and the phi coefficient for measuring correlation between the treatment group and the binary variable. We found that a standardized difference of 10% (or 0.1) is equivalent to having a phi coefficient of 0.05 (indicating negligible correlation) for the correlation between treatment group and the binary variable.     

Simulation studies:do data generation techniques play favourites?

When comparing the performances of several classification procedures utilizing simulated data, it is necessary to ensure that the method of data generation does not unfairly favor one or more of the procedures. This study was undertaken to examine the influence of five methods of generation of data with dichotomous independent variables and an ordinal response. One generation method considered was model-free and four were model-based; it was hypothesized that the model-based generation techniques would unfairly favor their respective underlying models. In the three outcome category situation, it was found that the interaction between generation procedure and classification model, although statistically significant, was always very small. Thus, these results indicate that the choice of generation procedure may usually be made based on issues other than potential interaction between generation procedure and classification model.     

An alternative approach to variable selection for prediction

A procedure for selecting a subset of predictor variables in regression analysis is suggested. The procedure is so designed that it leads to the selection of a subset of variables having an adequate degree of informativeness with a directly specified confidence coefficient. Some examples are considered to illustrate the application of the procedure.     

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.     

Hierarchical likelihood approach to non-Gaussian factor analysis

Factor models, structural equation models (SEMs) and random-effect models share the common feature that they assume latent or unobserved random variables. Factor models and SEMs allow well developed procedures for a rich class of covariance models with many parameters, while random-effect models allow well developed procedures for non-normal models including heavy-tailed distributions for responses and random effects. In this paper, we show how these two developments can be combined to result in an extremely rich class of models, which can be beneficial to both areas. A new fitting procedures for binary factor models and a robust estimation approach for continuous factor models are proposed.     

Concurrent generation of multivariate mixed data with variables of dissimilar types

ABSTRACT

Data sets originating from wide range of research studies are composed of multiple variables that are correlated and of dissimilar types, primarily of count, binary/ordinal and continuous attributes. The present paper builds on the previous works on multivariate data generation and develops a framework for generating multivariate mixed data with a pre-specified correlation matrix. The generated data consist of components that are marginally count, binary, ordinal and continuous, where the count and continuous variables follow the generalized Poisson and normal distributions, respectively. The use of the generalized Poisson distribution provides a flexible mechanism which allows under- and over-dispersed count variables generally encountered in practice. A step-by-step algorithm is provided and its performance is evaluated using simulated and real-data scenarios.     

Analysis of proportions for clustered binary data in the presence of unequal dispersions

This paper investigates the test procedures for testing the homogeneity of the proportions in the analysis of clustered binary data in the context of unequal dispersions across the treatment groups. We introduce a simple test procedure based on adjusted proportions using a sandwich estimator of the variance of the proportion estimators obtained by the generalized estimating equations approach of Zeger and Liang (1986) [Biometrics 42, 121-130]. We also extend the exiting test procedures of testing the hypothesis of proportions in this context. These test procedures are then compared, by simulations, in terms of size and power. Moreover, we derive the score test for testing the homogeneity of the dispersion parameters among several groups of clustered binary data. An illustrative application of the recommended test procedures is also presented.     

Bayesian latent variable models for clustered mixed outcomes

A general framework is proposed for modelling clustered mixed outcomes. A mixture of generalized linear models is used to describe the joint distribution of a set of underlying variables, and an arbitrary function relates the underlying variables to be observed outcomes. The model accommodates multilevel data structures, general covariate effects and distinct link functions and error distributions for each underlying variable. Within the framework proposed, novel models are developed for clustered multiple binary, unordered categorical and joint discrete and continuous outcomes. A Markov chain Monte Carlo sampling algorithm is described for estimating the posterior distributions of the parameters and latent variables. Because of the flexibility of the modelling framework and estimation procedure, extensions to ordered categorical outcomes and more complex data structures are straightforward. The methods are illustrated by using data from a reproductive toxicity study.     

Copula regression spline models for binary outcomes

We introduce a framework for estimating the effect that a binary treatment has on a binary outcome in the presence of unobserved confounding. The methodology is applied to a case study which uses data from the Medical Expenditure Panel Survey and whose aim is to estimate the effect of private health insurance on health care utilization. Unobserved confounding arises when variables which are associated with both treatment and outcome are not available (in economics this issue is known as endogeneity). Also, treatment and outcome may exhibit a dependence which cannot be modeled using a linear measure of association, and observed confounders may have a non-linear impact on the treatment and outcome variables. The problem of unobserved confounding is addressed using a two-equation structural latent variable framework, where one equation essentially describes a binary outcome as a function of a binary treatment whereas the other equation determines whether the treatment is received. Non-linear dependence between treatment and outcome is dealt using copula functions, whereas covariate-response relationships are flexibly modeled using a spline approach. Related model fitting and inferential procedures are developed, and asymptotic arguments presented.