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In many biomedical studies that involve correlated data, an outcome is often repeatedly measured for each individual subject along with the number of these measurements, which is also treated as an observed outcome. This type of data has been referred as multivariate random length data by Barnhart and Sampson (1995). A common approach to handling such type of data is to jointly model the multiple measurements and the random length. In previous literature, a key assumption is the multivariate normality for the multiple measurements. Motivated by a reproductive study, we propose a new copula-based joint model which relaxes the normality assumption. Specifically, we adopt the Clayton-Oakes model for multiple measurements with flexible marginal distributions specified as semi-parametric transformation models. The random length is modeled via a generalized linear model. We develop an approximate EM algorithm to derive parameter estimators and standard errors of the estimators are obtained through bootstrapping procedures and the finite-sample performance of the proposed method is investigated using simulation studies. We apply our method to the Mount Sinai Study of Women Office Workers (MSSWOW), where women were prospectively followed for 1 year for studying fertility.

Nonlinear mixed effects models have received a great deal of attention in the statistical literature in recent years because of their flexibility in handling longitudinal studies, including human immunodeficiency virus viral dynamics, pharmacokinetic analyses, and studies of growth and decay. A standard assumption in nonlinear mixed effects models for continuous responses is that the random effects and the within-subject errors are normally distributed, making the model sensitive to outliers. We present a novel class of asymmetric nonlinear mixed effects models that provides efficient parameters estimation in the analysis of longitudinal data. We assume that, marginally, the random effects follow a multivariate scale mixtures of skew-normal distribution and that the random errors follow a symmetric scale mixtures of normal distribution, providing an appealing robust alternative to the usual normal distribution. We propose an approximate method for maximum likelihood estimation based on an EM-type algorithm that produces approximate maximum likelihood estimates and significantly reduces the numerical difficulties associated with the exact maximum likelihood estimation. Techniques for prediction of future responses under this class of distributions are also briefly discussed. The methodology is illustrated through an application to Theophylline kinetics data and through some simulating studies.

The Expectation Maximisation (EM) algorithm is widely used to optimise non-convex likelihood functions with latent variables. Many authors modified its simple design to fit more specific situations. For instance, the Expectation (E) step has been replaced by Monte Carlo (MC), Markov Chain Monte Carlo or tempered approximations, etc. Most of the well-studied approximations belong to the stochastic class. By comparison, the literature is lacking when it comes to deterministic approximations. In this paper, we introduce a theoretical framework, with state-of-the-art convergence guarantees, for any deterministic approximation of the E step. We analyse theoretically and empirically several approximations that fit into this framework. First, for intractable E-steps, we introduce a deterministic version of MC-EM using Riemann sums. A straightforward method, not requiring any hyper-parameter fine-tuning, useful when the low dimensionality does not warrant a MC-EM. Then, we consider the tempered approximation, borrowed from the Simulated Annealing literature and used to escape local extrema. We prove that the tempered EM verifies the convergence guarantees for a wider range of temperature profiles than previously considered. We showcase empirically how new non-trivial profiles can more successfully escape adversarial initialisations. Finally, we combine the Riemann and tempered approximations into a method that accomplishes both their purposes.

In linear mixed models, the assumption of normally distributed random effects is often inappropriate and unnecessarily restrictive. The proposed approximate Dirichlet process mixture assumes a hierarchical Gaussian mixture that is based on the truncated version of the stick breaking presentation of the Dirichlet process. In addition to the weakening of distributional assumptions, the specification allows to identify clusters of observations with a similar random effects structure. An Expectation-Maximization algorithm is given that solves the estimation problem and that, in certain respects, may exhibit advantages over Markov chain Monte Carlo approaches when modelling with Dirichlet processes. The method is evaluated in a simulation study and applied to the dynamics of unemployment in Germany as well as lung function growth data.

Resampling techniques have the potential to provide useful information about the sampling distribution of estimators of many population characteristics. Ambitious schemes such as the bootstrap and iterated bootstrap imply a substantial increase in computational effort. For some iterative procedures, such as generalized least squares or the EM algorithm, it is possible to avoid fully iterating each bootstrap replication to convergence. By analysing expansions of the defining equation, we can extract asymptotically correct bootstrap estimates from a single step for each replication. In this paper we demonstrate the large sample validity of this computationally efficient approach and illustrate its small sample applicability. Whether or not the adjustment represents an adequate replacement for full iteration depends on the nature of the problem and the desired accuracy for the bootstrap quantiles. If subsequent iterations are adjusted, then greater enhancement of the rate is achieved and the practical increase in accuracy is significant.

We consider the problem of developing a simple approximation to a posterior distribution arising from incomplete data sampling. We compare approximations based on the normal distribution and upon conjugate distributions, theoretically where feasible and in some numerical examples. Two general conclusions can be made on the basis of our numerical work. First, when there is missing data, approximations which fail to take loss of information into account give overly concentrated posterior distributions. Second, the Gaussian approximation matching mode and observed Fisher information is quite good with large sample sizes and true posteriors which are not highly skewed. Further work delimiting these conditions more precisely will be useful. Finally, the use of a conjugate posterior which matches both mode and information performs well in all of our examples, and is decidedly superior to the Gaussian approximation with small samples.