Effect of assay measurement error on parameter estimation in concentration–QTc interval modeling

Linear mixed‐effects models (LMEMs) of concentration–double‐delta QTc intervals (QTc intervals corrected for placebo and baseline effects) assume that the concentration measurement error is negligible, which is an incorrect assumption. Previous studies have shown in linear models that independent variable error can attenuate the slope estimate with a corresponding increase in the intercept. Monte Carlo simulation was used to examine the impact of assay measurement error (AME) on the parameter estimates of an LMEM and nonlinear MEM (NMEM) concentration–ddQTc interval model from a ‘typical’ thorough QT study. For the LMEM, the type I error rate was unaffected by assay measurement error. Significant slope attenuation ( > 10%) occurred when the AME exceeded > 40% independent of the sample size. Increasing AME also decreased the between‐subject variance of the slope, increased the residual variance, and had no effect on the between‐subject variance of the intercept. For a typical analytical assay having an assay measurement error of less than 15%, the relative bias in the estimates of the model parameters and variance components was less than 15% in all cases. The NMEM appeared to be more robust to AME error as most parameters were unaffected by measurement error. Monte Carlo simulation was then used to determine whether the simulation–extrapolation method of parameter bias correction could be applied to cases of large AME in LMEMs. For analytical assays with large AME ( > 30%), the simulation–extrapolation method could correct biased model parameter estimates to near‐unbiased levels. Copyright © 2013 John Wiley & Sons, Ltd.     

The symmetric and asymmetric Choquet integrals on finite spaces for decision making

In this paper, we give a mathematical analysis of symmetric and asymmetric Choquet integrals in the view of decision making in a finite setting. These integrals present two ways of dealing with negative integrands. The analysis is done with the aid of the Möbius and interaction transforms, this last one having an interesting interpretation in multicriteria decision making (MCDM). The last part of the paper shows the application of these two integrals in MCDM.     

On a Comparison of Several Competing Estimates of a Univariate Normal Mean by the Multiple Criteria Decision-Making Method

In this article we consider the problem of estimation of the mean of a univariate normal population with an unknown variance when uncertain nonsample prior information about the mean is available. We compare four estimators of the mean, including pretest and shrinkage estimators. The performances of the estimators are compared based on the multiple criteria decision making (MCDM) procedure in order to find the best estimator.     

Deletion residuals in the detection of heterogeneity of variances in linear regression

The heterogeneity of error variance often causes a huge interpretive problem in linear regression analysis. Before taking any remedial measures we first need to detect this problem. A large number of diagnostic plots are now available in the literature for detecting heteroscedasticity of error variances. Among them the ‘residuals’ and ‘fits’ (R–F) plot is very popular and commonly used. In the R–F plot residuals are plotted against the fitted responses, where both these components are obtained using the ordinary least squares (OLS) method. It is now evident that the OLS fits and residuals suffer a huge setback in the presence of unusual observations and hence the R–F plot may not exhibit the real scenario. The deletion residuals based on a data set free from all unusual cases should estimate the true errors in a better way than the OLS residuals. In this paper we propose ‘deletion residuals’ and the ‘deletion fits’ (DR–DF) plot for the detection of the heterogeneity of error variances in a linear regression model to get a more convincing and reliable graphical display. Examples show that this plot locates unusual observations more clearly than the R–F plot. The advantage of using deletion residuals in the detection of heteroscedasticity of error variance is investigated through Monte Carlo simulations under a variety of situations.     

Geometric aspects of deletion diagnostics in multivariate regression

In multivariate regression, a graphical diagnostic method of detecting observations that are influential in estimating regression coefficients is introduced. It is based on the principal components and their variances obtained from the covariance matrix of the probability distribution for the change in the estimator of the matrix of unknown regression coefficients due to a single-case deletion. As a result, each deletion statistic obtained in a form of matrix is transformed into a two-dimensional quantity. Its univariate version is also introduced in a little different way. No distributional form is assumed. For illustration, we provide a numerical example in which the graphical method introduced here is seen to be effective in getting information about influential observations.     

Efficient estimation in a regression model with missing responses

This article examines methods to efficiently estimate the mean response in a linear model with an unknown error distribution under the assumption that the responses are missing at random. We show how the asymptotic variance is affected by the estimator of the regression parameter, and by the imputation method. To estimate the regression parameter, the ordinary least squares is efficient only if the error distribution happens to be normal. If the errors are not normal, then we propose a one step improvement estimator or a maximum empirical likelihood estimator to efficiently estimate the parameter.To investigate the imputation’s impact on the estimation of the mean response, we compare the listwise deletion method and the propensity score method (which do not use imputation at all), and two imputation methods. We demonstrate that listwise deletion and the propensity score method are inefficient. Partial imputation, where only the missing responses are imputed, is compared to full imputation, where both missing and non-missing responses are imputed. Our results reveal that, in general, full imputation is better than partial imputation. However, when the regression parameter is estimated very poorly, the partial imputation will outperform full imputation. The efficient estimator for the mean response is the full imputation estimator that utilizes an efficient estimator of the parameter.     

Multiple deletion measures and conditional influence in regression model

The joint effect of the deletion of the ith and jih cases is given by Gray and Ling (1984), they discussed the influence measures for influential subsets in linear regression analysis. The present paper is concerned with multiple sets of deletion measures in the linear regression model. In particular we are interested in the effects of the jointly and conditional influence analysis for the detection of two influential subsets.     

Identifying multiple influential observations in linear regression

The identification of influential observations has drawn a great deal of attention in regression diagnostics. Most of these identification techniques are based on single case deletion and among them DFFITS has become very popular with the statisticians. But this technique along with all other single case diagnostics may be ineffective in the presence of multiple influential observations. In this paper we develop a generalized version of DFFITS based on group deletion and then propose a new technique to identify multiple influential observations using this. The advantage of using the proposed method in the identification of multiple influential cases is then investigated through several well-referred data sets.     

Identification of multiple influential observations in logistic regression

The identification of influential observations in logistic regression has drawn a great deal of attention in recent years. Most of the available techniques like Cook's distance and difference of fits (DFFITS) are based on single-case deletion. But there is evidence that these techniques suffer from masking and swamping problems and consequently fail to detect multiple influential observations. In this paper, we have developed a new measure for the identification of multiple influential observations in logistic regression based on a generalized version of DFFITS. The advantage of the proposed method is then investigated through several well-referred data sets and a simulation study.     

multiple and conditional deletion diagnostics for general linear models

In this paper we develop multiple case deletion statistics for the general linear model so that a residual vector and a leverage matrix are identified which have roles analogous to residuals and leverage for ordinary least squares models. We extend the notion of the conditional deletion diagnostic to general linear models. The residuals, leverage and deletion diagnostics are illustrated with data modelled by a linear growth curve.     

Identification of Multiple Outliers in Logistic Regression

The use of logistic regression modeling has seen a great deal of attention in the literature in recent years. This includes all aspects of the logistic regression model including the identification of outliers. A variety of methods for the identification of outliers, such as the standardized Pearson residuals, are now available in the literature. These methods, however, are successful only if the data contain a single outlier. In the presence of multiple outliers in the data, which is often the case in practice, these methods fail to detect the outliers. This is due to the well-known problems of masking (false negative) and swamping (false positive) effects. In this article, we propose a new method for the identification of multiple outliers in logistic regression. We develop a generalized version of standardized Pearson residuals based on group deletion and then propose a technique for identifying multiple outliers. The performance of the proposed method is then investigated through several examples.     

A Simple Derivation of Deletion Diagnostic Results for the General Linear Model with Correlated Errors

A general, simple and intuitive derivation is provided for diagnostics associated with the deletion of arbitrary subsets for the linear model with general covariance structure. These are seen to be most simply expressed, even for the well-studied case of independent and identically distributed data, in terms of a residual known variously as the conditional residual, the deletion prediction residual and the cross-validation residual. Particularly simple specializations arise when the subsets are of size 1 and of size 2, but the method is easy to apply for all subsets and to conditional deletions.     

Influence diagnostics and outlier tests for semiparametric mixed models

Summary. Semiparametric mixed models are useful in biometric and econometric applications, especially for longitudinal data. Maximum penalized likelihood estimators (MPLEs) have been shown to work well by Zhang and co-workers for both linear coefficients and nonparametric functions. This paper considers the role of influence diagnostics in the MPLE by extending the case deletion and subject deletion analysis of linear models to accommodate the inclusion of a nonparametric component. We focus on influence measures for the fixed effects and provide formulae that are analogous to those for simpler models and readily computable with the MPLE algorithm. We also establish an equivalence between the case or subject deletion model and a mean shift outlier model from which we derive tests for outliers. The influence diagnostics proposed are illustrated through a longitudinal hormone study on progesterone and a simulated example.     

Residuals from deletion in added variable plots

An added variable plot is a commonly used plot in regression diagnostics. The rationale for this plot is to provide information about the addition of a further explanatory variable to the model. In addition, an added variable plot is most often used for detecting high leverage points and influential data. So far as we know, this type of plot involves the least squares residuals which, we suspect, could produce a confusing picture when a group of unusual cases are present in the data. In this situation, added variable plots may not only fail to detect the unusual cases but also may fail to focus on the need for adding a further regressor to the model. We suggest that residuals from deletion should be more convincing and reliable in this type of plot. The usefulness of an added variable plot based on residuals from deletion is investigated through a few examples and a Monte Carlo simulation experiment in a variety of situations.     

ON CROSS-VALIDATION FOR SMOOTHING SPLINES IN THE CASE OF DEPENDENT OBSERVATIONS

Cross-validation, as a popular tool for choosing a smoothing parameter, is generalized to the case of dependent observations. A general version of the ‘deletion theorem’ for representation and simplified calculation of cross-validatory criteria is given. Finally cross-validation is discussed in terms of penalized likelihoods as a method for model choice analogous to the Akaike information criterion.     

Modeling veterans’ health benefit grants using the expectation maximization algorithm

A novel application of the expectation maximization (EM) algorithm is proposed for modeling right-censored multiple regression. Parameter estimates, variability assessment, and model selection are summarized in a multiple regression settings assuming a normal model. The performance of this method is assessed through a simulation study. New formulas for measuring model utility and diagnostics are derived based on the EM algorithm. They include reconstructed coefficient of determination and influence diagnostics based on a one-step deletion method. A real data set, provided by North Dakota Department of Veterans Affairs, is modeled using the proposed methodology. Empirical findings should be of benefit to government policy-makers.     

A multiple-case deletion approach for detecting influential points in high-dimensional regression

ABSTRACT

In high-dimensional regression, the presence of influential observations may lead to inaccurate analysis results so that it is a prime and important issue to detect these unusual points before statistical regression analysis. Most of the traditional approaches are, however, based on single-case diagnostics, and they may fail due to the presence of multiple influential observations that suffer from masking effects. In this paper, an adaptive multiple-case deletion approach is proposed for detecting multiple influential observations in the presence of masking effects in high-dimensional regression. The procedure contains two stages. Firstly, we propose a multiple-case deletion technique, and obtain an approximate clean subset of the data that is presumably free of influential observations. To enhance efficiency, in the second stage, we refine the detection rule. Monte Carlo simulation studies and a real-life data analysis investigate the effective performance of the proposed procedure.     

Effect of individual observations on the Box–Cox transformation

In this paper, we consider the influence of individual observations on inferences about the Box–Cox power transformation parameter from a Bayesian point of view. We compare Bayesian diagnostic measures with the ‘forward’ method of analysis due to Riani and Atkinson. In particular, we look at the effect of omitting observations on the inference by comparing particular choices of transformation using the conditional predictive ordinate and the k _d measure of Pettit and Young. We illustrate the methods using a designed experiment. We show that a group of masked outliers can be detected using these single deletion diagnostics. Also, we show that Bayesian diagnostic measures are simpler to use to investigate the effect of observations on transformations than the forward search method.     

Node deletion sequences in influence diagrams using genetic algorithms

Influence diagrams are powerful tools for representing and solving complex inference and decision-making problems under uncertainty. They are directed acyclic graphs with nodes and arcs that have a precise meaning. The algorithm for evaluating an influence diagram deletes nodes from the graph in a particular order given by the position of each node and its arcs with respect to the value node. In many cases, however, there is more than one possible node deletion sequence. They all lead to the optimal solution of the problem, but may involve different computational efforts, which is a primary issue when facing real-size models. Finding the optimal deletion sequence is a NP-hard problem. The proposals given in the literature have proven to require complex transformations of the influence diagram. In this paper, we present a genetic algorithm-based approach, which merely has to be added to the influence diagram evaluation algorithm we use, and whose codification is straightforward. The experiments, varying parameters like crossover and mutation operators, population sizes and mutation rates, are analysed statistically, showing favourable results over existing heuristics.     

Identification of multiple high leverage points in logistic regression

Leverage values are being used in regression diagnostics as measures of unusual observations in the X-space. Detection of high leverage observations or points is crucial due to their responsibility for masking outliers. In linear regression, high leverage points (HLP) are those that stand far apart from the center (mean) of the data and hence the most extreme points in the covariate space get the highest leverage. But Hosemer and Lemeshow [Applied logistic regression, Wiley, New York, 1980] pointed out that in logistic regression, the leverage measure contains a component which can make the leverage values of genuine HLP misleadingly very small and that creates problem in the correct identification of the cases. Attempts have been made to identify the HLP based on the median distances from the mean, but since they are designed for the identification of a single high leverage point they may not be very effective in the presence of multiple HLP due to their masking (false–negative) and swamping (false–positive) effects. In this paper we propose a new method for the identification of multiple HLP in logistic regression where the suspect cases are identified by a robust group deletion technique and they are confirmed using diagnostic techniques. The usefulness of the proposed method is then investigated through several well-known examples and a Monte Carlo simulation.