Corrected profile likelihood confidence interval for binomial paired incomplete data

Clinical trials often use paired binomial data as their clinical endpoint. The confidence interval is frequently used to estimate the treatment performance. Tang et al. (2009) have proposed exact and approximate unconditional methods for constructing a confidence interval in the presence of incomplete paired binary data. The approach proposed by Tang et al. can be overly conservative with large expected confidence interval width (ECIW) in some situations. We propose a profile likelihood‐based method with a Jeffreys' prior correction to construct the confidence interval. This approach generates confidence interval with a much better coverage probability and shorter ECIWs. The performances of the method along with the corrections are demonstrated through extensive simulation. Finally, three real world data sets are analyzed by all the methods. Statistical Analysis System (SAS) codes to execute the profile likelihood‐based methods are also presented. Copyright © 2013 John Wiley & Sons, Ltd.     

Reproducibility of clinical data II: categorical outcomes

In this second part of this paper, reproducibility of discrete ordinal and nominal outcomes is addressed. The first part deals with continuous outcomes, concentrating on intraclass correlation (ρ) in the context of one‐way analysis of variance. For categorical data, the focus has generally not been on a meaningful population parameter such as ρ. However, intraclass correlation has been defined for discrete ordinal data, ρ_c, and for nominal data, κ_I. Therefore, a unified approach to reproducibility is proposed. The relevance of these parameters is outlined. Estimation and inferential procedures for ρ_c and κ_I are reviewed, together with worked examples. Topics related to reproducibility that are not addressed in either this or the previous paper are highlighted. Considerations for designing reproducibility studies and for interpreting their results are provided. Copyright © 2004 John Wiley & Sons, Ltd.     

A permutation test approach to the choice of size k for the nearest neighbors classifier

The k nearest neighbors (k-NN) classifier is one of the most popular methods for statistical pattern recognition and machine learning. In practice, the size k, the number of neighbors used for classification, is usually arbitrarily set to one or some other small numbers, or based on the cross-validation procedure. In this study, we propose a novel alternative approach to decide the size k. Based on a k-NN-based multivariate multi-sample test, we assign each k a permutation test based Z-score. The number of NN is set to the k with the highest Z-score. This approach is computationally efficient since we have derived the formulas for the mean and variance of the test statistic under permutation distribution for multiple sample groups. Several simulation and real-world data sets are analyzed to investigate the performance of our approach. The usefulness of our approach is demonstrated through the evaluation of prediction accuracies using Z-score as a criterion to select the size k. We also compare our approach to the widely used cross-validation approaches. The results show that the size k selected by our approach yields high prediction accuracies when informative features are used for classification, whereas the cross-validation approach may fail in some cases.     

On the asymptotic non‐equivalence of efficient‐GMM and MEL estimators in models with missing data

The generalized method of moments (GMM) and empirical likelihood (EL) are popular methods for combining sample and auxiliary information. These methods are used in very diverse fields of research, where competing theories often suggest variables satisfying different moment conditions. Results in the literature have shown that the efficient‐GMM (GMM_E) and maximum empirical likelihood (MEL) estimators have the same asymptotic distribution to order n^?1/2 and that both estimators are asymptotically semiparametric efficient. In this paper, we demonstrate that when data are missing at random from the sample, the utilization of some well‐known missing‐data handling approaches proposed in the literature can yield GMM_E and MEL estimators with nonidentical properties; in particular, it is shown that the GMM_E estimator is semiparametric efficient under all the missing‐data handling approaches considered but that the MEL estimator is not always efficient. A thorough examination of the reason for the nonequivalence of the two estimators is presented. A particularly strong feature of our analysis is that we do not assume smoothness in the underlying moment conditions. Our results are thus relevant to situations involving nonsmooth estimating functions, including quantile and rank regressions, robust estimation, the estimation of receiver operating characteristic (ROC) curves, and so on.     

Implementation of maximin efficient designs in dose‐finding studies

This paper considers the maximin approach for designing clinical studies. A maximin efficient design maximizes the smallest efficiency when compared with a standard design, as the parameters vary in a specified subset of the parameter space. To specify this subset of parameters in a real situation, a four‐step procedure using elicitation based on expert opinions is proposed. Further, we describe why and how we extend the initially chosen subset of parameters to a much larger set in our procedure. By this procedure, the maximin approach becomes feasible for dose‐finding studies. Maximin efficient designs have shown to be numerically difficult to construct. However, a new algorithm, the H‐algorithm, considerably simplifies the construction of these designs. We exemplify the maximin efficient approach by considering a sigmoid Emax model describing a dose–response relationship and compare inferential precision with that obtained when using a uniform design. The design obtained is shown to be at least 15% more efficient than the uniform design. © 2014 The Authors. Pharmaceutical Statistics Published by John Wiley & Sons Ltd.     

Bayesian variable selection in a finite mixture of linear mixed-effects models

Mixture of linear mixed-effects models has received considerable attention in longitudinal studies, including medical research, social science and economics. The inferential question of interest is often the identification of critical factors that affect the responses. We consider a Bayesian approach to select the important fixed and random effects in the finite mixture of linear mixed-effects models. To accomplish our goal, latent variables are introduced to facilitate the identification of influential fixed and random components and to classify the membership of observations in the longitudinal data. A spike-and-slab prior for the regression coefficients is adopted to sidestep the potential complications of highly collinear covariates and to handle large p and small n issues in the variable selection problems. Here we employ Markov chain Monte Carlo (MCMC) sampling techniques for posterior inferences and explore the performance of the proposed method in simulation studies, followed by an actual psychiatric data analysis concerning depressive disorder.     

Estimation of Correlation for Continuous Semimartingales

Abstract. In this study we are concerned with inference on the correlation parameter ρ of two Brownian motions, when only high‐frequency observations from two one‐dimensional continuous Itô semimartingales, driven by these particular Brownian motions, are available. Estimators for ρ are constructed in two situations: either when both components are observed (at the same time), or when only one component is observed and the other one represents its volatility process and thus has to be estimated from the data as well. In the first case it is shown that our estimator has the same asymptotic behaviour as the standard one for i.i.d. normal observations, whereas a feasible estimator can still be defined in the second framework, but with a slower rate of convergence.     

The asymptotic properties of the maximum-relevance weighted likelihood estimators

We define the maximum-relevance weighted likelihood estimator (MREWLE) using the relevance-weighted likelihood function introduced by Hu and Zidek (1995). Furthermore, we establish the consistency of the MREWLE under a wide range of conditions. Our results generalize those of Wald (1948) to both nonidentically distributed random variables and unequally weighted likelihoods (when dealing with independent data sets of varying relevance to the inferential problem of interest). Asymptotic normality is also proven. Applying these results to generalized smoothing model is discussed.     

Classification with minimum ambiguity under distribution heterogeneity

The traditional classification is based on the assumption that distribution of indicator variable X in one class is homogeneous. However, when data in one class comes from heterogeneous distribution, the likelihood ratio of two classes is not unique. In this paper, we construct the classification via an ambiguity criterion for the case of distribution heterogeneity of X in a single class. The separated historical data in each situation are used to estimate the thresholds respectively. The final boundary is chosen as the maximum and minimum thresholds from all situations. Our approach obtains the minimum ambiguity with a high classification accuracy allowing for a precise decision. In addition, nonparametric estimation of the classification region and theoretical properties are derived. Simulation study and real data analysis are reported to demonstrate the effectiveness of our method.     

Tests for noninferiority trials with binomial endpoints: A guide to modern and quasi‐exact methods for biomedical researchers

Applied statisticians and pharmaceutical researchers are frequently involved in the design and analysis of clinical trials where at least one of the outcomes is binary. Treatments are judged by the probability of a positive binary response. A typical example is the noninferiority trial, where it is tested whether a new experimental treatment is practically not inferior to an active comparator with a prespecified margin δ. Except for the special case of δ = 0, no exact conditional test is available although approximate conditional methods (also called second‐order methods) can be applied. However, in some situations, the approximation can be poor and the logical argument for approximate conditioning is not compelling. The alternative is to consider an unconditional approach. Standard methods like the pooled z‐test are already unconditional although approximate. In this article, we review and illustrate unconditional methods with a heavy emphasis on modern methods that can deliver exact, or near exact, results. For noninferiority trials based on either rate difference or rate ratio, our recommendation is to use the so‐called E‐procedure, based on either the score or likelihood ratio statistic. This test is effectively exact, computationally efficient, and respects monotonicity constraints in practice. We support our assertions with a numerical study, and we illustrate the concepts developed in theory with a clinical example in pulmonary oncology; R code to conduct all these analyses is available from the authors.     

An Objective Bayesian Criterion to Determine Model Prior Probabilities

We discuss the problem of selecting among alternative parametric models within the Bayesian framework. For model selection problems, which involve non‐nested models, the common objective choice of a prior on the model space is the uniform distribution. The same applies to situations where the models are nested. It is our contention that assigning equal prior probability to each model is over simplistic. Consequently, we introduce a novel approach to objectively determine model prior probabilities, conditionally, on the choice of priors for the parameters of the models. The idea is based on the notion of the worth of having each model within the selection process. At the heart of the procedure is the measure of this worth using the Kullback–Leibler divergence between densities from different models.     

Sample size calculation for an agreement study

It is often necessary to compare two measurement methods in medicine and other experimental sciences. This problem covers a broad range of data. Many authors have explored ways of assessing the agreement of two sets of measurements. However, there has been relatively little attention to the problem of determining sample size for designing an agreement study. In this paper, a method using the interval approach for concordance is proposed to calculate sample size in conducting an agreement study. The philosophy behind this is that the concordance is satisfied when no more than the pre‐specified k discordances are found for a reasonable large sample size n since it is much easier to define a discordance pair. The goal here is to find such a reasonable large sample size n. The sample size calculation is based on two rates: the discordance rate and tolerance probability, which in turn can be used to quantify an agreement study. The proposed approach is demonstrated through a real data set. Copyright © 2009 John Wiley & Sons, Ltd.     

On Nonsmooth Estimating Functions via Jackknife Empirical Likelihood

In many applications, the parameters of interest are estimated by solving non‐smooth estimating functions with U‐statistic structure. Because the asymptotic covariances matrix of the estimator generally involves the underlying density function, resampling methods are often used to bypass the difficulty of non‐parametric density estimation. Despite its simplicity, the resultant‐covariance matrix estimator depends on the nature of resampling, and the method can be time‐consuming when the number of replications is large. Furthermore, the inferences are based on the normal approximation that may not be accurate for practical sample sizes. In this paper, we propose a jackknife empirical likelihood‐based inferential procedure for non‐smooth estimating functions. Standard chi‐square distributions are used to calculate the p‐value and to construct confidence intervals. Extensive simulation studies and two real examples are provided to illustrate its practical utilities.     

Model‐based linear clustering

The authors propose a profile likelihood approach to linear clustering which explores potential linear clusters in a data set. For each linear cluster, an errors‐in‐variables model is assumed. The optimization of the derived profile likelihood can be achieved by an EM algorithm. Its asymptotic properties and its relationships with several existing clustering methods are discussed. Methods to determine the number of components in a data set are adapted to this linear clustering setting. Several simulated and real data sets are analyzed for comparison and illustration purposes. The Canadian Journal of Statistics 38: 716–737; 2010 © 2010 Statistical Society of Canada     

A heteroscedastic structural errors-in-variables model with equation error

It is not uncommon with astrophysical and epidemiological data sets that the variances of the observations are accessible from an analytical treatment of the data collection process. Moreover, in a regression model, heteroscedastic measurement errors and equation errors are common situations when modelling such data. This article deals with the limiting distribution of the maximum-likelihood and method-of-moments estimators for the line parameters of the regression model. We use the delta method to achieve it, making it possible to build joint confidence regions and hypothesis testing. This technique produces closed expressions for the asymptotic covariance matrix of those estimators. In the moment approach we do not assign any distribution for the unobservable covariate while with the maximum-likelihood approach, we assume a normal distribution. We also conduct simulation studies of rejection rates for Wald-type statistics in order to verify the test size and power. Practical applications are reported for a data set produced by the Chandra observatory and also from the WHO MONICA Project on cardiovascular disease.     

Bayesian estimation for time-series regressions improved with exact likelihoods

We propose an estimation procedure for time-series regression models under the Bayesian inference framework. With the exact method of Wise [Wise, J. (1955). The autocorrelation function and spectral density function. Biometrika, 42, 151–159], an exact likelihood function can be obtained instead of the likelihood conditional on initial observations. The constraints on the parameter space arising from the stationarity conditions are handled by a reparametrization, which was not taken into consideration by Chib [Chib, S. (1993). Bayes regression with autoregressive errors: A Gibbs sampling approach. J. Econometrics, 58, 275–294] or Chib and Greenberg [Chib, S. and Greenberg, E. (1994). Bayes inference in regression model with ARMA(p, q) errors. J. Econometrics, 64, 183–206]. Simulation studies show that our method leads to better inferential results than their results.     

Large‐sample tests of extreme‐value dependence for multivariate copulas

Starting from the characterization of extreme‐value copulas based on max‐stability, large‐sample tests of extreme‐value dependence for multivariate copulas are studied. The two key ingredients of the proposed tests are the empirical copula of the data and a multiplier technique for obtaining approximate p‐values for the derived statistics. The asymptotic validity of the multiplier approach is established, and the finite‐sample performance of a large number of candidate test statistics is studied through extensive Monte Carlo experiments for data sets of dimension two to five. In the bivariate case, the rejection rates of the best versions of the tests are compared with those of the test of Ghoudi et al. (1998) recently revisited by Ben Ghorbal et al. (2009). The proposed procedures are illustrated on bivariate financial data and trivariate geological data. The Canadian Journal of Statistics 39: 703–720; 2011. © 2011 Statistical Society of Canada     

Comparing two treatments by decision theory

Decision theory is applied to the general problem of comparing two treatments in an experiment with subjects assigned to the treatments at random. The inferential agenda covers collection of evidence about superiority, non‐inferiority and average bioequivalence of the treatments. The proposed approach requires defining the terms ‘small’ and ‘large’ to qualify the magnitude of the treatment effect and specifying the losses (or loss functions) that quantify the consequences of the incorrect conclusions. We argue that any analysis that ignores these two inputs is deficient, and so is any ad hoc way of taking them into account. Sample size calculation for studies intended to be analysed by this approach is also discussed. Copyright © 2016 John Wiley & Sons, Ltd.     

Fast tensorial JADE

We propose a novel method for tensorial‐independent component analysis. Our approach is based on TJADE and k‐JADE, two recently proposed generalizations of the classical JADE algorithm. Our novel method achieves the consistency and the limiting distribution of TJADE under mild assumptions and at the same time offers notable improvement in computational speed. Detailed mathematical proofs of the statistical properties of our method are given and, as a special case, a conjecture on the properties of k‐JADE is resolved. Simulations and timing comparisons demonstrate remarkable gain in speed. Moreover, the desired efficiency is obtained approximately for finite samples. The method is applied successfully to large‐scale video data, for which neither TJADE nor k‐JADE is feasible. Finally, an experimental procedure is proposed to select the values of a set of tuning parameters. Supplementary material including the R‐code for running the examples and the proofs of the theoretical results is available online.     

Assessing the pattern of covariance matrices via an augmentation multiple testing procedure

This paper extends the scedasticity comparison among several groups of observations, usually complying with the homoscedastic and the heteroscedastic cases, in order to deal with data sets laying in an intermediate situation. As is well known, homoscedasticity corresponds to equality in orientation, shape and size of the group scatters. Here our attention is focused on two weaker requirements: scatters with the same orientation, but with different shape and size, or scatters with the same shape and size but different orientation. We introduce a multiple testing procedure that takes into account each of the above conditions. This approach discloses a richer information on the data underlying structure than the classical method only based on homo/heteroscedasticity. At the same time, it allows a more parsimonious parametrization, whenever the patterned model is appropriate to describe the real data. The new inferential methodology is then applied to some well-known data sets, chosen in the multivariate literature, to show the real gain in using this more informative approach. Finally, a wide simulation study illustrates and compares the performance of the proposal using data sets with gradual departure from homoscedasticity.