A generalisation of T‐optimality for discriminating between competing models with an application to pharmacokinetic studies

The T‐optimality criterion is used in optimal design to derive designs for model selection. To set up the method, it is required that one of the models is considered to be true. We term this local T‐optimality. In this work, we propose a generalisation of T‐optimality (termed robust T‐optimality) that relaxes the requirement that one of the candidate models is set as true. We then show an application to a nonlinear mixed effects model with two candidate non‐nested models and combine robust T‐optimality with robust D‐optimality. Optimal design under local T‐optimality was found to provide adequate power when the a priori assumed true model was the true model but poor power if the a priori assumed true model was not the true model. The robust T‐optimality method provided adequate power irrespective of which model was true. The robust T‐optimality method appears to have useful properties for nonlinear models, where both the parameter values and model structure are required to be known a priori, and the most likely model that would be applied to any new experiment is not known with certainty. Copyright © 2012 John Wiley & Sons, Ltd.     

Efficient circular neighbour designs for spatial interference model

We consider circular block designs for field-trials when there are two-sided spatial interference between neighbouring plots of the same blocks. The parameter of interest is total effects that is the sum of direct effect of treatment and neighbour effects, which correspond to the use of a single treatment in the whole field. We determine universally optimal approximate designs. When the number of blocks may be large, we propose efficient exact designs generated by a single sequence of treatment. We also give efficiency factors of the usual binary block neighbour balanced designs which can be used when the number of blocks is small.     

Efficient designs based on orthogonal arrays of type I and type II for experiments using units ordered over time or space

For a wide variety of applications, experiments are based on units ordered over time or space. Models for these experiments generally may include one or more of: correlations, systematic trends, carryover effects and interference effects. Since the standard optimal block designs may not be efficient in these situations, orthogonal arrays of type I and type II, which were introduced in 1961 by C.R. Rao [Combinatorial arrangements analogous to orthogonal arrays, Sankhya A 23 (1961) 283–286], have been recently used to construct optimal and efficient designs for many of these experiments. Results in this area are unified and the salient features are outlined.     

The ℓ1 oblique procrustes problem

In this paper, we reconsider the well-known oblique Procrustes problem where the usual least-squares objective function is replaced by a more robust discrepancy measure, based on the ₁ norm or smooth approximations of it.We propose two approaches to the solution of this problem. One approach is based on convex analysis and uses the structure of the problem to permit a solution to the ₁ norm problem. An alternative approach is to smooth the problem by working with smooth approximations to the ₁ norm, and this leads to a solution process based on the solution of ordinary differential equations on manifolds. The general weighted Procrustes problem (both orthogonal and oblique) can also be solved by the latter approach. Numerical examples to illustrate the algorithms which have been developed are reported and analyzed.     

Optimal designs for tumor regrowth models

Most growth curves can only be used to model the tumor growth under no intervention. To model the growth curves for treated tumor, both the growth delay due to the treatment and the regrowth of the tumor after the treatment need to be taken into account. In this paper, we consider two tumor regrowth models and determine the locally D- and c-optimal designs for these models. We then show that the locally D- and c-optimal designs are minimally supported. We also consider two equally spaced designs as alternative designs and evaluate their efficiencies.     

ROC Curves in Non‐Parametric Location‐Scale Regression Models

Abstract. The receiver operating characteristic (ROC) curve is a tool of extensive use to analyse the discrimination capability of a diagnostic variable in medical studies. In certain situations, the presence of a covariate related to the diagnostic variable can increase the discriminating power of the ROC curve. In this article, we model the effect of the covariate over the diagnostic variable by means of non‐parametric location‐scale regression models. We propose a new non‐parametric estimator of the conditional ROC curve and study its asymptotic properties. We also present some simulations and an illustration to a data set concerning diagnosis of diabetes.     

Measurement Error Correction by Exploiting Gene–Environment Independence in Family‐Based Case–Control Studies

Abstract. Family‐based case–control designs are commonly used in epidemiological studies for evaluating the role of genetic susceptibility and environmental exposure to risk factors in the etiology of rare diseases. Within this framework, it is often reasonable to assume genetic susceptibility and environmental exposure being conditionally independent of each other within families in the source population. We focus on this setting to explore the situation of measurement error affecting the assessment of the environmental exposure. We correct for measurement error through a likelihood‐based method. We exploit a conditional likelihood approach to relate the probability of disease to the genetic and the environmental risk factors. We show that this approach provides less biased and more efficient results than that based on logistic regression. Regression calibration, instead, provides severely biased estimators of the parameters. The comparison of the correction methods is performed through simulation, under common measurement error structures.     

Estimation of a Conditional Copula and Association Measures

Abstarct. This paper is concerned with studying the dependence structure between two random variables Y ₁ and Y ₂ conditionally upon a covariate X. The dependence structure is modelled via a copula function, which depends on the given value of the covariate in a general way. Gijbels et al. (Comput. Statist. Data Anal., 55, 2011, 1919) suggested two non‐parametric estimators of the ‘conditional’ copula and investigated their numerical performances. In this paper we establish the asymptotic properties of the proposed estimators as well as conditional association measures derived from them. Practical recommendations for their use are then discussed.     

Polynomial Spline Estimation for a Generalized Additive Coefficient Model

Abstract.  We study a semiparametric generalized additive coefficient model (GACM), in which linear predictors in the conventional generalized linear models are generalized to unknown functions depending on certain covariates, and approximate the non-parametric functions by using polynomial spline. The asymptotic expansion with optimal rates of convergence for the estimators of the non-parametric part is established. Semiparametric generalized likelihood ratio test is also proposed to check if a non-parametric coefficient can be simplified as a parametric one. A conditional bootstrap version is suggested to approximate the distribution of the test under the null hypothesis. Extensive Monte Carlo simulation studies are conducted to examine the finite sample performance of the proposed methods. We further apply the proposed model and methods to a data set from a human visceral Leishmaniasis study conducted in Brazil from 1994 to 1997. Numerical results outperform the traditional generalized linear model and the proposed GACM is preferable.     

Pseudo-empirical Bayes estimation of small area means under a nested error linear regression model with functional measurement errors

Small area estimation is studied under a nested error linear regression model with area level covariate subject to measurement error. Ghosh and Sinha (2007) obtained a pseudo-Bayes (PB) predictor of a small area mean and a corresponding pseudo-empirical Bayes (PEB) predictor, using the sample means of the observed covariate values to estimate the true covariate values. In this paper, we first derive an efficient PB predictor by using all the available data to estimate true covariate values. We then obtain a corresponding PEB predictor and show that it is asymptotically “optimal”. In addition, we employ a jackknife method to estimate the mean squared prediction error (MSPE) of the PEB predictor. Finally, we report the results of a simulation study on the performance of our PEB predictor and associated jackknife MSPE estimator. Our results show that the proposed PEB predictor can lead to significant gain in efficiency over the previously proposed PEB predictor. Area level models are also studied.