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.     

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.     

Parameter estimation from interval-valued data using the expectation-maximization algorithm

This paper investigates on the problem of parameter estimation in statistical model when observations are intervals assumed to be related to underlying crisp realizations of a random sample. The proposed approach relies on the extension of likelihood function in interval setting. A maximum likelihood estimate of the parameter of interest may then be defined as a crisp value maximizing the generalized likelihood function. Using the expectation-maximization (EM) to solve such maximizing problem therefore derives the so-called interval-valued EM algorithm (IEM), which makes it possible to solve a wide range of statistical problems involving interval-valued data. To show the performance of IEM, the following two classical problems are illustrated: univariate normal mean and variance estimation from interval-valued samples, and multiple linear/nonlinear regression with crisp inputs and interval output.     

Small-sample intervals for regression

For the general linear regression model Y = Xη + e, we construct small-sample exponentially tilted empirical confidence intervals for a linear parameter 6 = a^Tη and for nonlinear functions of η. The coverage error for the intervals is O_p(1/n), as shown in Tingley and Field (1990). The technique, though sample-based, does not require bootstrap resampling. The first step is calculation of an estimate for η. We have used a Mallows estimate. The algorithm applies whenever η is estimated as the solution of a system of equations having expected value 0. We include calculations of the relative efficiency of the estimator (compared with the classical least-squares estimate). The intervals are compared with asymptotic intervals as found, for example, in Hampel et at. (1986). We demonstrate that the procedure gives sensible intervals for small samples.     

Efficient Rank Regression with Wavelet Estimated Scores

We provide an estimate of the score function for rank regression using compactly supported wavelets. This estimate is then used to find a rank-based asymptotically efficient estimator for the slope parameter of a linear model. We also provide a consistent estimator of the asymptotic variance of the rank estimator. For related mixed models, the asymptotic relative efficiency is also discussed     

Estimation of the Variance Function in Heteroscedastic Linear Regression Models

Heteroscedasticity generally exists when a linear regression model is applied to analyzing some real-world problems. Therefore, how to accurately estimate the variance functions of the error term in a heteroscedastic linear regression model is of great importance for obtaining efficient estimates of the regression parameters and making valid statistical inferences. A method for estimating the variance function of heteroscedastic linear regression models is proposed in this article based on the variance-reduced local linear smoothing technique. Some simulations and comparisons with other method are conducted to assess the performance of the proposed method. The results demonstrate that the proposed method can accurately estimate the variance functions and therefore produce more efficient estimates of the regression parameters.     

Reducing errors-in-variables bias in linear regression using compact genetic algorithms

A new technique is devised to mitigate the errors-in-variables bias in linear regression. The procedure mimics a 2-stage least squares procedure where an auxiliary regression which generates a better behaved predictor variable is derived. The generated variable is then used as a substitute for the error-prone variable in the first-stage model. The performance of the algorithm is tested by simulation and regression analyses. Simulations suggest the algorithm efficiently captures the additive error term used to contaminate the artificial variables. Regressions provide further credit to the simulations as they clearly show that the compact genetic algorithm-based estimate of the true but unobserved regressor yields considerably better results. These conclusions are robust across different sample sizes and different variance structures imposed on both the measurement error and regression disturbances.     

Estimation in multiple linear regression Berkson model for processes with uncorrelated increments

This paper presents a method of estimating the regression and variance parameters in the multiple linear regression Berkson model for a continuous-time stochastic process with uncorrelated increments. Under minimal conditions, we establish (i) the Gauss–Markov theorem and the quadratic mean—as well as the strong consistency of the proposed estimate of the regression parameter and (ii) the weak consistency of the proposed estimate of the variance parameter.     

SEMIPARAMETRIC ESTIMATION OF THE ERROR DISTRIBUTION IN MULTIVARIATE REGRESSION USING COPULAS

A semiparametric method is developed to estimate the dependence parameter and the joint distribution of the error term in the multivariate linear regression model. The nonparametric part of the method treats the marginal distributions of the error term as unknown, and estimates them using suitable empirical distribution functions. Then the dependence parameter is estimated by either maximizing a pseudolikelihood or solving an estimating equation. It is shown that this estimator is asymptotically normal, and a consistent estimator of its large sample variance is given. A simulation study shows that the proposed semiparametric method is better than the parametric ones available when the error distribution is unknown, which is almost always the case in practice. It turns out that there is no loss of asymptotic efficiency as a result of the estimation of regression parameters. An empirical example on portfolio management is used to illustrate the method.     

Error variance estimation via least squares for small sample nonparametric regression

In this paper we explore statistical properties of some difference-based approaches to estimate an error variance for small sample based on nonparametric regression which satisfies Lipschitz condition. Our study is motivated by Tong and Wang (2005), who estimated error variance using a least squares approach. They considered the error variance as the intercept in a simple linear regression which was obtained from the expectation of their lag-k Rice estimator. Their variance estimators are highly dependent on the setting of a regressor and weight of their simple linear regression. Although this regressor and weight can be varied based on the characteristic of an unknown nonparametric mean function, Tong and Wang (2005) have used a fixed regressor and weight in a large sample and gave no indication of how to determine the regressor and the weight. In this paper, we propose a new approach via local quadratic approximation to determine this regressor and weight. Using our proposed regressor and weight, we estimate the error variance as the intercept of simple linear regression using both ordinary least squares and weighted least squares. Our approach applies to both small and large samples, while most existing difference-based methods are appropriate solely for large samples. We compare the performance of our approach with other existing approaches using extensive simulation study. The advantage of our approach is demonstrated using a real data set.     

Variance Reduction in Smoothing Splines

Abstract.  We develop a variance reduction method for smoothing splines. For a given point of estimation, we define a variance-reduced spline estimate as a linear combination of classical spline estimates at three nearby points. We first develop a variance reduction method for spline estimators in univariate regression models. We then develop an analogous variance reduction method for spline estimators in clustered/longitudinal models. Simulation studies are performed which demonstrate the efficacy of our variance reduction methods in finite sample settings. Finally, a real data analysis with the motorcycle data set is performed. Here we consider variance estimation and generate 95% pointwise confidence intervals for the unknown regression function.     

Choice of the ridge factor from the correlation matrix determinant

Ridge regression is the alternative method to ordinary least squares, which is mostly applied when a multiple linear regression model presents a worrying degree of collinearity. A relevant topic in ridge regression is the selection of the ridge parameter, and different proposals have been presented in the scientific literature. Since the ridge estimator is biased, its estimation is normally based on the calculation of the mean square error (MSE) without considering (to the best of our knowledge) whether the proposed value for the ridge parameter really mitigates the collinearity. With this goal and different simulations, this paper proposes to estimate the ridge parameter from the determinant of the matrix of correlation of the data, which verifies that the variance inflation factor (VIF) is lower than the traditionally established threshold. The possible relation between the VIF and the determinant of the matrix of correlation is also analysed. Finally, the contribution is illustrated with three real examples.     

Empirical Likelihood Based Rank Regression Inference

Rank regression procedures have been proposed and studied for numerous research applications that do not satisfy the underlying assumptions of the more common linear regression models. This article develops confidence regions for the slope parameter of rank regression using an empirical likelihood (EL) ratio method. It has the advantage of not requiring variance estimation which is required for the normal approximation method. The EL method is also range respecting and results in asymmetric confidence intervals. Simulation studies are used to compare and evaluate normal approximation versus EL inference methods for various conditions such as different sample size or error distribution. The simulation study demonstrates our proposed EL method almost outperforms the traditional method in terms of coverage probability, lower-tail side error, and upper-tail side error. An application of stability analysis also shows the EL method results in shorter confidence intervals for real life data.     

AN EXAMINATION OF ESTIMATED RESIDUALS IN A REGRESSION WITH AN INFINITE ORDER PARAMETRIC MODEL

We consider a linear regression with the error term that obeys an autoregressive model of infinite order and estimate parameters of the models. The parameters of the autoregressive model should be estimated based on estimated residuals obtained by means of the method of ordinary least squares, because the errors are unobservable. The consistency of the coefficients, variance and spectral density of the model obeyed by the error term is shown. Further, we estimate the coefficients of the linear regression by means of the method of estimated generalized least squares. We also show the consistency of the estimator.

     

The effects of model mis-specifications in linear measurement error models

In the literature, there are many results on the consequences of mis-specified models for linear models with error in the response only, see, e.g., Seber(1977). There are also discussions of estimation for the model writh errors both in the response and in the predictor variables (called measurement error models; see, e.g., Fuller(1987)). In this paper, we consider the problem of model mis-specification for measurement error models. Only a few special cases have been tackled in the past (Edland, 1996; Carroll and Ruppert, 1996 and Lakshminarayanan Amp; Gunst, 1984); we deal with the situation here in some generality. Results have been obtained as follows: (a) When a model is under-fitted, the estimate of the variance of the measurement error will be asymptotically biased, as will the regression coefficients, and the asymptotic biases in the estimates of the regression coefficients will always exist for under-fitted models. Even orthogonality of the variables in the model will not make the biases vanish. (b)For over-fitting, the estimates of the variances of measurement errors and of the regression coefficients are asymptotically unbiased. However, the variance of the estimated regression coefficients will increase. Over-fitting will cause larger changes in the variances of the estimated parameters in measurement error models than in no measurement error models.     

A comparison of estimators for regression models with change points

We consider two problems concerning locating change points in a linear regression model. One involves jump discontinuities (change-point) in a regression model and the other involves regression lines connected at unknown points. We compare four methods for estimating single or multiple change points in a regression model, when both the error variance and regression coefficients change simultaneously at the unknown point(s): Bayesian, Julious, grid search, and the segmented methods. The proposed methods are evaluated via a simulation study and compared via some standard measures of estimation bias and precision. Finally, the methods are illustrated and compared using three real data sets. The simulation and empirical results overall favor both the segmented and Bayesian methods of estimation, which simultaneously estimate the change point and the other model parameters, though only the Bayesian method is able to handle both continuous and dis-continuous change point problems successfully. If it is known that regression lines are continuous then the segmented method ranked first among methods.     

Semiparametric jump-preserving estimation for single-index models

Estimation of the single-index model with a discontinuous unknown link function is considered in this paper. Existed refined minimum average variance estimation (rMAVE) method can estimate the single-index parameter and unknown link function simultaneously by minimising the average pointwise conditional variance, where the conditional variance can be estimated using the local linear fit method with centred kernel function. When there are jumps in the link function, big biases around jumps can appear. For this reason, we embed the jump-preserving technique in the rMAVE method, then propose an adaptive jump-preserving estimation procedure for the single-index model. Concretely speaking, the conditional variance is obtained by the one among local linear fits with centred, left-sided and right-sided kernel functions who has minimum weighted residual mean squares. The resulting estimators can preserve the jumps well and also give smooth estimates of the continuity parts. Asymptotic properties are established under some mild conditions. Simulations and real data analysis show the proposed method works well.     

Confidence Sets Based on Thresholding Estimators in High-Dimensional Gaussian Regression Models

We study confidence intervals based on hard-thresholding, soft-thresholding, and adaptive soft-thresholding in a linear regression model where the number of regressors k may depend on and diverge with sample size n. In addition to the case of known error variance, we define and study versions of the estimators when the error variance is unknown. In the known-variance case, we provide an exact analysis of the coverage properties of such intervals in finite samples. We show that these intervals are always larger than the standard interval based on the least-squares estimator. Asymptotically, the intervals based on the thresholding estimators are larger even by an order of magnitude when the estimators are tuned to perform consistent variable selection. For the unknown-variance case, we provide nontrivial lower bounds and a small numerical study for the coverage probabilities in finite samples. We also conduct an asymptotic analysis where the results from the known-variance case can be shown to carry over asymptotically if the number of degrees of freedom n ? k tends to infinity fast enough in relation to the thresholding parameter.     

Estimation of regression parameters in generalized linear models for cluster correlated data with measurement error

Liang and Zeger (1986) introduced a class of estimating equations that gives consistent estimates of regression parameters and of their asymptotic variances in the class of generalized linear models for cluster correlated data. When the independent variables or covariates in such models are subject to measurement errors, the parameter estimates obtained from these estimating equations are no longer consistent. To correct for the effect of measurement errors, an estimator with smaller asymptotic bias is constructed along the lines of Stefanski (1985), assuming that the measurement error variance is either known or estimable. The asymptotic distribution of the bias-corrected estimator and a consistent estimator of its asymptotic variance are also given. The special case of a binary logistic regression model is studied in detail. For this case, methods based on conditional scores and quasilikelihood are also extended to cluster correlated data. Results of a small simulation study on the performance of the proposed estimators and associated tests of hypotheses are reported.