Estimation of Some Nonlinear Panel Data Models With Both Time-Varying and Time-Invariant Explanatory Variables

The so-called “fixed effects” approach to the estimation of panel data models suffers from the limitation that it is not possible to estimate the coefficients on explanatory variables that are time-invariant. This is in contrast to a “random effects” approach, which achieves this by making much stronger assumptions on the relationship between the explanatory variables and the individual-specific effect. In a linear model, it is possible to obtain the best of both worlds by making random effects-type assumptions on the time-invariant explanatory variables while maintaining the flexibility of a fixed effects approach when it comes to the time-varying covariates. This article attempts to do the same for some popular nonlinear models.     

Nonlinear mixed‐effects models with misspecified random‐effects distribution

Nonlinear mixed‐effects models are being widely used for the analysis of longitudinal data, especially from pharmaceutical research. They use random effects which are latent and unobservable variables so the random‐effects distribution is subject to misspecification in practice. In this paper, we first study the consequences of misspecifying the random‐effects distribution in nonlinear mixed‐effects models. Our study is focused on Gauss‐Hermite quadrature, which is now the routine method for calculation of the marginal likelihood in mixed models. We then present a formal diagnostic test to check the appropriateness of the assumed random‐effects distribution in nonlinear mixed‐effects models, which is very useful for real data analysis. Our findings show that the estimates of fixed‐effects parameters in nonlinear mixed‐effects models are generally robust to deviations from normality of the random‐effects distribution, but the estimates of variance components are very sensitive to the distributional assumption of random effects. Furthermore, a misspecified random‐effects distribution will either overestimate or underestimate the predictions of random effects. We illustrate the results using a real data application from an intensive pharmacokinetic study.     

A flexible semiparametric regression model for bimodal,asymmetric and censored data

In this paper, we propose a new semiparametric heteroscedastic regression model allowing for positive and negative skewness and bimodal shapes using the B-spline basis for nonlinear effects. The proposed distribution is based on the generalized additive models for location, scale and shape framework in order to model any or all parameters of the distribution using parametric linear and/or nonparametric smooth functions of explanatory variables. We motivate the new model by means of Monte Carlo simulations, thus ignoring the skewness and bimodality of the random errors in semiparametric regression models, which may introduce biases on the parameter estimates and/or on the estimation of the associated variability measures. An iterative estimation process and some diagnostic methods are investigated. Applications to two real data sets are presented and the method is compared to the usual regression methods.     

Path analysis and determining the distribution of indirect effects via simulation

The difference between a path analysis and the other multivariate analyses is that the path analysis has the ability to compute the indirect effects apart from the direct effects. The aim of this study is to investigate the distribution of indirect effects that is one of the components of path analysis via generated data. To realize this, a simulation study has been conducted with four different sample sizes, three different numbers of explanatory variables and with three different correlation matrices. A replication of 1000 has been applied for every single combination. According to the results obtained, it is found that irrespective of the sample size path coefficients tend to be stable. Moreover, path coefficients are not affected by correlation types either. Since the replication number is 1000, which is fairly large, the indirect effects from the path models have been treated as normal and their confidence intervals have been presented as well. It is also found that the path analysis should not be used with three explanatory variables. We think that this study would help scientists who are working in both natural and social sciences to determine sample size and different number of variables in the path analysis.     

A statistical model for orientation mechanism

A variance components model with response variable depending on both fixed effects of explanatory variables and random components is specified to model longitudinal circular data, in order to study the directional behaviour of small animals, as insects, crustaceans, amphipods, etc. Unknown parameter estimators are obtained using a simulated maximum likelihood approach. Issues concerning log-likelihood variability and the related problems in the optimization algorithm are also addressed. The procedure is applied to the analysis of directional choices under full natural conditions ofTalitrus saltator from Castiglione della Pescaia (Italy) beaches.     

Deconvolution methods for non-parametric inference in two-level mixed models

Summary.  We develop a general non-parametric approach to the analysis of clustered data via random effects. Assuming only that the link function is known, the regression functions and the distributions of both cluster means and observation errors are treated non-parametrically. Our argument proceeds by viewing the observation error at the cluster mean level as though it were a measurement error in an errors-in-variables problem, and using a deconvolution argument to access the distribution of the cluster mean. A Fourier deconvolution approach could be used if the distribution of the error-in-variables were known. In practice it is unknown, of course, but it can be estimated from repeated measurements, and in this way deconvolution can be achieved in an approximate sense. This argument might be interpreted as implying that large numbers of replicates are necessary for each cluster mean distribution, but that is not so; we avoid this requirement by incorporating statistical smoothing over values of nearby explanatory variables. Empirical rules are developed for the choice of smoothing parameter. Numerical simulations, and an application to real data, demonstrate small sample performance for this package of methodology. We also develop theory establishing statistical consistency.     

Approximate bounded influence estimation for longitudinal data with outliers and measurement errors

Mixed effects models or random effects models are popular for the analysis of longitudinal data. In practice, longitudinal data are often complex since there may be outliers in both the response and the covariates and there may be measurement errors. The likelihood method is a common approach for these problems but it can be computationally very intensive and sometimes may even be computationally infeasible. In this article, we consider approximate robust methods for nonlinear mixed effects models to simultaneously address outliers and measurement errors. The approximate methods are computationally very efficient. We show the consistency and asymptotic normality of the approximate estimates. The methods can also be extended to missing data problems. An example is used to illustrate the methods and a simulation is conducted to evaluate the methods.     

Nonlinear measures of association with kernel canonical correlation analysis and applications

Measures of association between two sets of random variables have long been of interest to statisticians. The classical canonical correlation analysis (LCCA) can characterize, but also is limited to, linear association. This article introduces a nonlinear and nonparametric kernel method for association study and proposes a new independence test for two sets of variables. This nonlinear kernel canonical correlation analysis (KCCA) can also be applied to the nonlinear discriminant analysis. Implementation issues are discussed. We place the implementation of KCCA in the framework of classical LCCA via a sequence of independent systems in the kernel associated Hilbert spaces. Such a placement provides an easy way to carry out the KCCA. Numerical experiments and comparison with other nonparametric methods are presented.     

High dimensional variable selection with clustered data: an application of random multivariate survival forests for detection of outlier medical device components

In many medical studies patients are nested or clustered within doctor. With many explanatory variables, variable selection with clustered data can be challenging. We propose a method for variable selection based on random forest that addresses clustered data through stratified binary splits. Our motivating example involves the detection orthopedic device components from a large pool of candidates, where each patient belongs to a surgeon. Simulations compare the performance of survival forests grown using the stratified logrank statistic to conventional and robust logrank statistics, as well as a method to select variables using a threshold value based on a variable's empirical null distribution. The stratified logrank test performs superior to conventional and robust methods when data are generated to have cluster-specific effects, and when cluster sizes are sufficiently large, perform comparably to the splitting alternatives in the absence of cluster-specific effects. Thresholding was effective at distinguishing between important and unimportant variables.     

Residual-based specification of the random-effects distribution for cluster data

We propose a method for specifying the distribution of random effects included in a model for cluster data. The class of models we consider includes mixed models and frailty models whose random effects and explanatory variables are constant within clusters. The method is based on cluster residuals obtained by assuming that the random effects are equal between clusters. We exhibit an asymptotic relationship between the cluster residuals and variations of the random effects as the number of observations increases and the variance of the random effects decreases. The asymptotic relationship is used to specify the random-effects distribution. The method is applied to a frailty model and a model used to describe the spread of plant diseases.     

Resampling m-Dependent Random Variables with Applications to Forecasting

Resampling methods are proposed to estimate the distributions of sums of m -dependent possibly differently distributed real-valued random variables. The random variables are allowed to have varying mean values. A non parametric resampling method based on the moving blocks bootstrap is proposed for the case in which the mean values are smoothly varying or 'asymptotically equal'. The idea is to resample blocks in pairs. It is also confirmed that a 'circular' block resampling scheme can be used in the case where the mean values are 'asymptotically equal'. A central limit resampling theorem for each of the two cases is proved. The resampling methods have a potential application to time series analysis, to distinguish between two different forecasting models. This is illustrated with an example using Swedish export prices of coated paper products.     

A unified approach to estimation of nonlinear mixed effects and Berkson measurement error models

Mixed effects models and Berkson measurement error models are widely used. They share features which the author uses to develop a unified estimation framework. He deals with models in which the random effects (or measurement errors) have a general parametric distribution, whereas the random regression coefficients (or unobserved predictor variables) and error terms have nonparametric distributions. He proposes a second-order least squares estimator and a simulation-based estimator based on the first two moments of the conditional response variable given the observed covariates. He shows that both estimators are consistent and asymptotically normally distributed under fairly general conditions. The author also reports Monte Carlo simulation studies showing that the proposed estimators perform satisfactorily for relatively small sample sizes. Compared to the likelihood approach, the proposed methods are computationally feasible and do not rely on the normality assumption for random effects or other variables in the model.     

Regression models for Boolean random sets

In this paper we consider the regression problem for random sets of the Boolean-model type. Regression modeling of the Boolean random sets using some explanatory variables are classified according to the type of these variables as propagation, growth or propagation-growth models. The maximum likelihood estimation of the parameters for the propagation model is explained in detail for some specific link functions using three methods. These three methods of estimation are also compared in a simulation study.     

Ordering and selecting components in multivariate or functional data linear prediction

Summary.  The problem of component choice in regression-based prediction has a long history. The main cases where important choices must be made are functional data analysis, and problems in which the explanatory variables are relatively high dimensional vectors. Indeed, principal component analysis has become the basis for methods for functional linear regression. In this context the number of components can also be interpreted as a smoothing parameter, and so the viewpoint is a little different from that for standard linear regression. However, arguments for and against conventional component choice methods are relevant to both settings and have received significant recent attention. We give a theoretical argument, which is applicable in a wide variety of settings, justifying the conventional approach. Although our result is of minimax type, it is not asymptotic in nature; it holds for each sample size. Motivated by the insight that is gained from this analysis, we give theoretical and numerical justification for cross-validation choice of the number of components that is used for prediction. In particular we show that cross-validation leads to asymptotic minimization of mean summed squared error, in settings which include functional data analysis.     

Score test of homogeneity for survival data

If follow-up is made for subjects which are grouped into units, such as familial or spatial units then it may be interesting to test whether the groups are homogeneous (or independent for given explanatory variables). The effect of the groups is modelled as random and we consider a frailty proportional hazards model which allows to adjust for explanatory variables. We derive the score test of homogeneity from the marginal partial likelihood and it turns out to be the sum of a pairwise correlation term of martingale residuals and an overdispersion term. In the particular case where the sizes of the groups are equal to one, this statistic can be used for testing overdispersion. The asymptotic variance of this statistic is derived using counting process arguments. An extension to the case of several strata is given. The resulting test is computationally simple; its use is illustrated using both simulated and real data. In addition a decomposition of the score statistic is proposed as a sum of a pairwise correlation term and an overdispersion term. The pairwise correlation term can be used for constructing a statistic more robust to departure from the proportional hazard model, and the overdispesion term for constructing a test of fit of the proportional hazard model.     

Generalized additive models for location, scale and shape

Summary.  A general class of statistical models for a univariate response variable is presented which we call the generalized additive model for location, scale and shape (GAMLSS). The model assumes independent observations of the response variable y given the parameters, the explanatory variables and the values of the random effects. The distribution for the response variable in the GAMLSS can be selected from a very general family of distributions including highly skew or kurtotic continuous and discrete distributions. The systematic part of the model is expanded to allow modelling not only of the mean (or location) but also of the other parameters of the distribution of y , as parametric and/or additive nonparametric (smooth) functions of explanatory variables and/or random-effects terms. Maximum (penalized) likelihood estimation is used to fit the (non)parametric models. A Newton–Raphson or Fisher scoring algorithm is used to maximize the (penalized) likelihood. The additive terms in the model are fitted by using a backfitting algorithm. Censored data are easily incorporated into the framework. Five data sets from different fields of application are analysed to emphasize the generality of the GAMLSS class of models.     

Gaussian Markov random field spatial models in GAMLSS

This paper describes the modelling and fitting of Gaussian Markov random field spatial components within a Generalized AdditiveModel for Location, Scale and Shape (GAMLSS) model. This allows modelling of any or all the parameters of the distribution for the response variable using explanatory variables and spatial effects. The response variable distribution is allowed to be a non-exponential family distribution. A new package developed in R to achieve this is presented. We use Gaussian Markov random fields to model the spatial effect in Munich rent data and explore some features and characteristics of the data. The potential of using spatial analysis within GAMLSS is discussed. We argue that the flexibility of parametric distributions, ability to model all the parameters of the distribution and diagnostic tools of GAMLSS provide an ideal environment for modelling spatial features of data.     

Functional Partial Linear Single‐index Model

This paper deals with the problem of predicting the real‐valued response variable using explanatory variables containing both multivariate random variable and random curve. The proposed functional partial linear single‐index model treats the multivariate random variable as linear part and the random curve as functional single‐index part, respectively. To estimate the non‐parametric link function, the functional single‐index and the parameters in the linear part, a two‐stage estimation procedure is proposed. Compared with existing semi‐parametric methods, the proposed approach requires no initial estimation and iteration. Asymptotical properties are established for both the parameters in the linear part and the functional single‐index. The convergence rate for the non‐parametric link function is also given. In addition, asymptotical normality of the error variance is obtained that facilitates the construction of confidence region and hypothesis testing for the unknown parameter. Numerical experiments including simulation studies and a real‐data analysis are conducted to evaluate the empirical performance of the proposed method.     

Errors-in-variables beta regression models

Beta regression models provide an adequate approach for modeling continuous outcomes limited to the interval (0, 1). This paper deals with an extension of beta regression models that allow for explanatory variables to be measured with error. The structural approach, in which the covariates measured with error are assumed to be random variables, is employed. Three estimation methods are presented, namely maximum likelihood, maximum pseudo-likelihood and regression calibration. Monte Carlo simulations are used to evaluate the performance of the proposed estimators and the naïve estimator. Also, a residual analysis for beta regression models with measurement errors is proposed. The results are illustrated in a real data set.     

A Bayesian approach for generalized linear models with explanatory biomarker measurement variables subject to detection limit: an application to acute lung injury

Biomarkers have the potential to improve our understanding of disease diagnosis and prognosis. Biomarker levels that fall below the assay detection limits (DLs), however, compromise the application of biomarkers in research and practice. Most existing methods to handle non-detects focus on a scenario in which the response variable is subject to the DL; only a few methods consider explanatory variables when dealing with DLs. We propose a Bayesian approach for generalized linear models with explanatory variables subject to lower, upper, or interval DLs. In simulation studies, we compared the proposed Bayesian approach to four commonly used methods in a logistic regression model with explanatory variable measurements subject to the DL. We also applied the Bayesian approach and other four methods in a real study, in which a panel of cytokine biomarkers was studied for their association with acute lung injury (ALI). We found that IL8 was associated with a moderate increase in risk for ALI in the model based on the proposed Bayesian approach.