Mixed-effects models for censored data with autoregressive errors.

Mixed-effects models, with modifications to accommodate censored observations (LMEC/NLMEC), are routinely used to analyze measurements, collected irregularly over time, which are often subject to some upper and lower detection limits. This paper presents a likelihood-based approach for fitting LMEC/NLMEC models with autoregressive of order p dependence of the error term. An EM-type algorithm is developed for computing the maximum likelihood estimates, obtaining as a byproduct the standard errors of the fixed effects and the likelihood value. Moreover, the constraints on the parameter space that arise from the stationarity conditions for the autoregressive parameters in the EM algorithm are handled by a reparameterization scheme, as discussed in Lin and Lee (2007). To examine the performance of the proposed method, we present some simulation studies and analyze a real AIDS case study. The proposed algorithm and methods are implemented in the new R package ARpLMEC.

Inference and diagnostics for heteroscedastic nonlinear regression models under skew scale mixtures of normal distributions.

The heteroscedastic nonlinear regression model (HNLM) is an important tool in data modeling. In this paper we propose a HNLM considering skew scale mixtures of normal (SSMN) distributions, which allows fitting asymmetric and heavy-tailed data simultaneously. Maximum likelihood (ML) estimation is performed via the expectation-maximization (EM) algorithm. The observed information matrix is derived analytically to account for standard errors. In addition, diagnostic analysis is developed using case-deletion measures and the local influence approach. A simulation study is developed to verify the empirical distribution of the likelihood ratio statistic, the power of the homogeneity of variances test and a study for misspecification of the structure function. The method proposed is also illustrated by analyzing a real dataset.

Censored linear regression models for irregularly observed longitudinal data using the multivariate- t distribution.

In acquired immunodeficiency syndrome (AIDS) studies it is quite common to observe viral load measurements collected irregularly over time. Moreover, these measurements can be subjected to some upper and/or lower detection limits depending on the quantification assays. A complication arises when these continuous repeated measures have a heavy-tailed behavior. For such data structures, we propose a robust structure for a censored linear model based on the multivariate Student's t-distribution. To compensate for the autocorrelation existing among irregularly observed measures, a damped exponential correlation structure is employed. An efficient expectation maximization type algorithm is developed for computing the maximum likelihood estimates, obtaining as a by-product the standard errors of the fixed effects and the log-likelihood function. The proposed algorithm uses closed-form expressions at the E-step that rely on formulas for the mean and variance of a truncated multivariate Student's t-distribution. The methodology is illustrated through an application to an Human Immunodeficiency Virus-AIDS (HIV-AIDS) study and several simulation studies.

Heteroscedastic nonlinear regression models based on scale mixtures of skew-normal distributions.

An extension of some standard likelihood based procedures to heteroscedastic nonlinear regression models under scale mixtures of skew-normal (SMSN) distributions is developed. We derive a simple EM-type algorithm for iteratively computing maximum likelihood (ML) estimates and the observed information matrix is derived analytically. Simulation studies demonstrate the robustness of this flexible class against outlying and influential observations, as well as nice asymptotic properties of the proposed EM-type ML estimates. Finally, the methodology is illustrated using an ultrasonic calibration data.