Semiparametric Bayesian hierarchical models for heterogeneous population in nonlinear mixed effect model: application to gastric emptying studies

Gastric emptying studies are frequently used in medical research, both human and animal, when evaluating the effectiveness and determining the unintended side-effects of new and existing medications, diets, and procedures or interventions. It is essential that gastric emptying data be appropriately summarized before making comparisons between study groups of interest and to allow study the comparisons. Since gastric emptying data have a nonlinear emptying curve and are longitudinal data, nonlinear mixed effect (NLME) models can accommodate both the variation among measurements within individuals and the individual-to-individual variation. However, the NLME model requires strong assumptions that are often not satisfied in real applications that involve a relatively small number of subjects, have heterogeneous measurement errors, or have large variation among subjects. Therefore, we propose three semiparametric Bayesian NLMEs constructed with Dirichlet process priors, which automatically cluster sub-populations and estimate heterogeneous measurement errors. To compare three semiparametric models with the parametric model we propose a penalized posterior Bayes factor. We compare the performance of our semiparametric hierarchical Bayesian approaches with that of the parametric Bayesian hierarchical approach. Simulation results suggest that our semiparametric approaches are more robust and flexible. Our gastric emptying studies from equine medicine are used to demonstrate the advantage of our approaches.     

A Spline‐Based Semiparametric Maximum Likelihood Estimation Method for the Cox Model with Interval‐Censored Data

Abstract. We propose a spline‐based semiparametric maximum likelihood approach to analysing the Cox model with interval‐censored data. With this approach, the baseline cumulative hazard function is approximated by a monotone B‐spline function. We extend the generalized Rosen algorithm to compute the maximum likelihood estimate. We show that the estimator of the regression parameter is asymptotically normal and semiparametrically efficient, although the estimator of the baseline cumulative hazard function converges at a rate slower than root‐n. We also develop an easy‐to‐implement method for consistently estimating the standard error of the estimated regression parameter, which facilitates the proposed inference procedure for the Cox model with interval‐censored data. The proposed method is evaluated by simulation studies regarding its finite sample performance and is illustrated using data from a breast cosmesis study.     

Efficiency in estimation of memory

We study the efficiency of semiparametric estimates of memory parameter. We propose a class of shift invariant tapers of order (p,q). For a fixed p, the variance inflation factor of the new tapers approaches 1 as q   goes to infinity. We show that for d∈(−1/2,p+1/2)$d\in (-1/2,p+1/2)$, the proposed tapered Gaussian semiparametric estimator has the same limiting distribution as the nontapered version for d∈(−1/2,1/2)$d\in (-1/2,1/2)$. The new estimator is mean and polynomial trend invariant, and is computationally advantageous in comparison to the recently proposed exact local Whittle estimator. The simulation study shows that our estimator has comparable or better mean squared error in finite samples for a variety of models.     

Uniformly adaptive estimation for models with arma errors

A semiparametric estimator based on an unknown density isuniformly adaptive if the expected loss of the estimator converges to the asymptotic expected loss of the maximum liklihood estimator based on teh true density (MLE), and if convergence does not depend on either the parameter values or the form of the unknown density. Without uniform adaptivity, the asymptotic expected loss of the MLE need not approximate the expected loss of a semiparametric estimator for any finite sample I show that a two step semiparametric estimator is uniformly adaptive for the parameters of nonlinear regression models with autoregressive moving average errors.     

Computing nonparametric functional estimates in semiparametric problems

The purpose of this note is to provide a brief account of available FORTRAN Routines for computing nonparametric functional estimates, Frequently used in semiparametric problems, evaluated at each data point. Then semiparametric estimates can be computed employing the use-favored economic software.     

Estimation in Semiparametric Marginal Shared Gamma Frailty Models

The semiparametric marginal shared frailty models in survival analysis have the non–parametric hazard functions multiplied by a random frailty in each cluster, and the survival times conditional on frailties are assumed to be independent. In addition, the marginal hazard functions have the same form as in the usual Cox proportional hazard models. In this paper, an approach based on maximum likelihood and expectation–maximization is applied to semiparametric marginal shared gamma frailty models, where the frailties are assumed to be gamma distributed with mean 1 and variance θ. The estimates of the fixed–effect parameters and their standard errors obtained using this approach are compared in terms of both bias and efficiency with those obtained using the extended marginal approach. Similarly, the standard errors of our frailty variance estimates are found to compare favourably with those obtained using other methods. The asymptotic distribution of the frailty variance estimates is shown to be a 50–50 mixture of a point mass at zero and a truncated normal random variable on the positive axis for θ₀ = 0. Simulations demonstrate that, for θ₀ < 0, it is approximately an x −(100 − x )%, 0 ≤ x ≤ 50, mixture between a point mass at zero and a truncated normal random variable on the positive axis for small samples and small values of θ₀; otherwise, it is approximately normal.     

Semiparametric estimation in copula models

The author recalls the limiting behaviour of the empirical copula process and applies it to prove some asymptotic properties of a minimum distance estimator for a Euclidean parameter in a copula model. The estimator in question is semiparametric in that no knowledge of the marginal distributions is necessary. The author also proposes another semiparametric estimator which he calls “rank approximate Z‐estimator” and whose asymptotic normality he derives. He further presents Monte Carlo simulation results for the comparison of various estimators in four well‐known bivariate copula models.     

Parameter estimation for semiparametric ordinary differential equation models

Abstract

We propose a new class of two-stage parameter estimation methods for semiparametric ordinary differential equation (ODE) models. In the first stage, state variables are estimated using a penalized spline approach; In the second stage, form of numerical discretization algorithms for an ODE solver is used to formulate estimating equations. Estimated state variables from the first stage are used to obtain more data points for the second stage. Asymptotic properties for the proposed estimators are established. Simulation studies show that the method performs well, especially for small sample. Real life use of the method is illustrated using Influenza specific cell-trafficking study.     

Variable selection for semiparametric errors-in-variables regression model with longitudinal data

In this paper, we focus on the variable selection for the semiparametric regression model with longitudinal data when some covariates are measured with errors. A new bias-corrected variable selection procedure is proposed based on the combination of the quadratic inference functions and shrinkage estimations. With appropriate selection of the tuning parameters, we establish the consistency and asymptotic normality of the resulting estimators. Extensive Monte Carlo simulation studies are conducted to examine the finite sample performance of the proposed variable selection procedure. We further illustrate the proposed procedure with an application.     

Testing the linearity of negative binomial regression models

The negative binomial (NB) is frequently used to model overdispersed Poisson count data. To study the effect of a continuous covariate of interest in an NB model, a flexible procedure is used to model the covariate effect by fixed-knot cubic basis-splines or B-splines with a second-order difference penalty on the adjacent B-spline coefficients to avoid undersmoothing. A penalized likelihood is used to estimate parameters of the model. A penalized likelihood ratio test statistic is constructed for the null hypothesis of the linearity of the continuous covariate effect. When the number of knots is fixed, its limiting null distribution is the distribution of a linear combination of independent chi-squared random variables, each with one degree of freedom. The smoothing parameter value is determined by setting a specified value equal to the asymptotic expectation of the test statistic under the null hypothesis. The power performance of the proposed test is studied with simulation experiments.