ASYMPTOTIC LIKELIHOOD APPROXIMATIONS USING A PARTIAL LAPLACE APPROXIMATION

Elimination of a nuisance variable is often non‐trivial and may involve the evaluation of an intractable integral. One approach to evaluate these integrals is to use the Laplace approximation. This paper concentrates on a new approximation, called the partial Laplace approximation, that is useful when the integrand can be partitioned into two multiplicative disjoint functions. The technique is applied to the linear mixed model and shows that the approximate likelihood obtained can be partitioned to provide a conditional likelihood for the location parameters and a marginal likelihood for the scale parameters equivalent to restricted maximum likelihood (REML). Similarly, the partial Laplace approximation is applied to the t‐distribution to obtain an approximate REML for the scale parameter. A simulation study reveals that, in comparison to maximum likelihood, the scale parameter estimates of the t‐distribution obtained from the approximate REML show reduced bias.     

Shape Constrained Non‐parametric Estimators of the Baseline Distribution in Cox Proportional Hazards Model

Abstract. We investigate non‐parametric estimation of a monotone baseline hazard and a decreasing baseline density within the Cox model. Two estimators of a non‐decreasing baseline hazard function are proposed. We derive the non‐parametric maximum likelihood estimator and consider a Grenander type estimator, defined as the left‐hand slope of the greatest convex minorant of the Breslow estimator. We demonstrate that the two estimators are strongly consistent and asymptotically equivalent and derive their common limit distribution at a fixed point. Both estimators of a non‐increasing baseline hazard and their asymptotic properties are obtained in a similar manner. Furthermore, we introduce a Grenander type estimator for a non‐increasing baseline density, defined as the left‐hand slope of the least concave majorant of an estimator of the baseline cumulative distribution function, derived from the Breslow estimator. We show that this estimator is strongly consistent and derive its asymptotic distribution at a fixed point.     

Estimating the variance for heterogeneity in arm‐based network meta‐analysis

Network meta‐analysis can be implemented by using arm‐based or contrast‐based models. Here we focus on arm‐based models and fit them using generalized linear mixed model procedures. Full maximum likelihood (ML) estimation leads to biased trial‐by‐treatment interaction variance estimates for heterogeneity. Thus, our objective is to investigate alternative approaches to variance estimation that reduce bias compared with full ML. Specifically, we use penalized quasi‐likelihood/pseudo‐likelihood and hierarchical (h) likelihood approaches. In addition, we consider a novel model modification that yields estimators akin to the residual maximum likelihood estimator for linear mixed models. The proposed methods are compared by simulation, and 2 real datasets are used for illustration. Simulations show that penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood reduce bias and yield satisfactory coverage rates. Sum‐to‐zero restriction and baseline contrasts for random trial‐by‐treatment interaction effects, as well as a residual ML‐like adjustment, also reduce bias compared with an unconstrained model when ML is used, but coverage rates are not quite as good. Penalized quasi‐likelihood/pseudo‐likelihood and h‐likelihood are therefore recommended.     

Empirical Likelihood Local Polynomial Regression Analysis of Clustered Data

Abstract. In this article, a naive empirical likelihood ratio is constructed for a non‐parametric regression model with clustered data, by combining the empirical likelihood method and local polynomial fitting. The maximum empirical likelihood estimates for the regression functions and their derivatives are obtained. The asymptotic distributions for the proposed ratio and estimators are established. A bias‐corrected empirical likelihood approach to inference for the parameters of interest is developed, and the residual‐adjusted empirical log‐likelihood ratio is shown to be asymptotically chi‐squared. These results can be used to construct a class of approximate pointwise confidence intervals and simultaneous bands for the regression functions and their derivatives. Owing to our bias correction for the empirical likelihood ratio, the accuracy of the obtained confidence region is not only improved, but also a data‐driven algorithm can be used for selecting an optimal bandwidth to estimate the regression functions and their derivatives. A simulation study is conducted to compare the empirical likelihood method with the normal approximation‐based method in terms of coverage accuracies and average widths of the confidence intervals/bands. An application of this method is illustrated using a real data set.     

Enhancements of Non‐parametric Generalized Likelihood Ratio Test: Bias Correction and Dimension Reduction

Non‐parametric generalized likelihood ratio test is a popular method of model checking for regressions. However, there are two issues that may be the barriers for its powerfulness: existing bias term and curse of dimensionality. The purpose of this paper is thus twofold: a bias reduction is suggested and a dimension reduction‐based adaptive‐to‐model enhancement is recommended to promote the power performance. The proposed test statistic still possesses the Wilks phenomenon and behaves like a test with only one covariate. Thus, it converges to its limit at a much faster rate and is much more sensitive to alternative models than the classical non‐parametric generalized likelihood ratio test. As a by‐product, we also prove that the bias‐corrected test is more efficient than the one without bias reduction in the sense that its asymptotic variance is smaller. Simulation studies and a real data analysis are conducted to evaluate of proposed tests.     

Inference on Survival Data with Covariate Measurement Error – An Imputation-based Approach

Abstract.  We propose a new method for fitting proportional hazards models with error-prone covariates. Regression coefficients are estimated by solving an estimating equation that is the average of the partial likelihood scores based on imputed true covariates. For the purpose of imputation, a linear spline model is assumed on the baseline hazard. We discuss consistency and asymptotic normality of the resulting estimators, and propose a stochastic approximation scheme to obtain the estimates. The algorithm is easy to implement, and reduces to the ordinary Cox partial likelihood approach when the measurement error has a degenerate distribution. Simulations indicate high efficiency and robustness. We consider the special case where error-prone replicates are available on the unobserved true covariates. As expected, increasing the number of replicates for the unobserved covariates increases efficiency and reduces bias. We illustrate the practical utility of the proposed method with an Eastern Cooperative Oncology Group clinical trial where a genetic marker, c- myc expression level, is subject to measurement error.     

Simplex Mixed‐Effects Models for Longitudinal Proportional Data

Abstract. Continuous proportional outcomes are collected from many practical studies, where responses are confined within the unit interval (0,1). Utilizing Barndorff‐Nielsen and Jørgensen's simplex distribution, we propose a new type of generalized linear mixed‐effects model for longitudinal proportional data, where the expected value of proportion is directly modelled through a logit function of fixed and random effects. We establish statistical inference along the lines of Breslow and Clayton's penalized quasi‐likelihood (PQL) and restricted maximum likelihood (REML) in the proposed model. We derive the PQL/REML using the high‐order multivariate Laplace approximation, which gives satisfactory estimation of the model parameters. The proposed model and inference are illustrated by simulation studies and a data example. The simulation studies conclude that the fourth order approximate PQL/REML performs satisfactorily. The data example shows that Aitchison's technique of the normal linear mixed model for logit‐transformed proportional outcomes is not robust against outliers.     

Empirical likelihood for the varying‐coefficient single‐index model

In this article the author investigates the application of the empirical‐likelihood‐based inference for the parameters of varying‐coefficient single‐index model (VCSIM). Unlike the usual cases, if there is no bias correction the asymptotic distribution of the empirical likelihood ratio cannot achieve the standard chi‐squared distribution. To this end, a bias‐corrected empirical likelihood method is employed to construct the confidence regions (intervals) of regression parameters, which have two advantages, compared with those based on normal approximation, that is, (1) they do not impose prior constraints on the shape of the regions; (2) they do not require the construction of a pivotal quantity and the regions are range preserving and transformation respecting. A simulation study is undertaken to compare the empirical likelihood with the normal approximation in terms of coverage accuracies and average areas/lengths of confidence regions/intervals. A real data example is given to illustrate the proposed approach. The Canadian Journal of Statistics 38: 434–452; 2010 © 2010 Statistical Society of Canada     

A Cox‐Aalen Model for Interval‐censored Data

The Cox‐Aalen model, obtained by replacing the baseline hazard function in the well‐known Cox model with a covariate‐dependent Aalen model, allows for both fixed and dynamic covariate effects. In this paper, we examine maximum likelihood estimation for a Cox‐Aalen model based on interval‐censored failure times with fixed covariates. The resulting estimator globally converges to the truth slower than the parametric rate, but its finite‐dimensional component is asymptotically efficient. Numerical studies show that estimation via a constrained Newton method performs well in terms of both finite sample properties and processing time for moderate‐to‐large samples with few covariates. We conclude with an application of the proposed methods to assess risk factors for disease progression in psoriatic arthritis.     

Empirical likelihood confidence regions in the single-index model with growing dimensions

This paper investigates statistical inference for the single-index model when the number of predictors grows with sample size. Empirical likelihood method for constructing confidence region for the index vector, which does not require a multivariate non parametric smoothing, is employed. However, the classical empirical likelihood ratio for this model does not remain valid because plug-in estimation of an infinite-dimensional nuisance parameter causes a non negligible bias and the diverging number of parameters/predictors makes the limit not chi-squared any more. To solve these problems, we define an empirical likelihood ratio based on newly proposed weighted estimating equations and show that it is asymptotically normal. Also we find that different weights used in the weighted residuals require, for asymptotic normality, different diverging rate of the number of predictors. However, the rate n^1/3, which is a possible fastest rate when there are no any other conditions assumed in the setting under study, is still attainable. A simulation study is carried out to assess the performance of our method.     

Fitting Cox Models with Doubly Censored Data Using Spline‐Based Sieve Marginal Likelihood

In some applications, the failure time of interest is the time from an originating event to a failure event while both event times are interval censored. We propose fitting Cox proportional hazards models to this type of data using a spline‐based sieve maximum marginal likelihood, where the time to the originating event is integrated out in the empirical likelihood function of the failure time of interest. This greatly reduces the complexity of the objective function compared with the fully semiparametric likelihood. The dependence of the time of interest on time to the originating event is induced by including the latter as a covariate in the proportional hazards model for the failure time of interest. The use of splines results in a higher rate of convergence of the estimator of the baseline hazard function compared with the usual non‐parametric estimator. The computation of the estimator is facilitated by a multiple imputation approach. Asymptotic theory is established and a simulation study is conducted to assess its finite sample performance. It is also applied to analyzing a real data set on AIDS incubation time.     

A hybrid method to estimate the full parametric hazard model

Abstract

In this paper, we propose a hybrid method to estimate the baseline hazard for Cox proportional hazard model. In the proposed method, the nonparametric estimate of the survival function by Kaplan Meier, and the parametric estimate of the logistic function in the Cox proportional hazard by partial likelihood method are combined to estimate a parametric baseline hazard function. We compare the estimated baseline hazard using the proposed method and the Cox model. The results show that the estimated baseline hazard using hybrid method is improved in comparison with estimated baseline hazard using the Cox model. The performance of each method is measured based on the estimated parameters of the baseline distribution as well as goodness of fit of the model. We have used real data as well as simulation studies to compare performance of both methods. Monte Carlo simulations carried out in order to evaluate the performance of the proposed method. The results show that the proposed hybrid method provided better estimate of the baseline in comparison with the estimated values by the Cox model.     

Estimation and prediction for spatial generalized linear mixed models using high order Laplace approximation

Estimation and prediction in generalized linear mixed models are often hampered by intractable high dimensional integrals. This paper provides a framework to solve this intractability, using asymptotic expansions when the number of random effects is large. To that end, we first derive a modified Laplace approximation when the number of random effects is increasing at a lower rate than the sample size. Second, we propose an approximate likelihood method based on the asymptotic expansion of the log-likelihood using the modified Laplace approximation which is maximized using a quasi-Newton algorithm. Finally, we define the second order plug-in predictive density based on a similar expansion to the plug-in predictive density and show that it is a normal density. Our simulations show that in comparison to other approximations, our method has better performance. Our methods are readily applied to non-Gaussian spatial data and as an example, the analysis of the rhizoctonia root rot data is presented.     

Likelihood inference for small variance components

The authors explore likelihood‐based methods for making inferences about the components of variance in a general normal mixed linear model. In particular, they use local asymptotic approximations to construct confidence intervals for the components of variance when the components are close to the boundary of the parameter space. In the process, they explore the question of how to profile the restricted likelihood (REML). Also, they show that general REML estimates are less likely to fall on the boundary of the parameter space than maximum‐likelihood estimates and that the likelihood‐ratio test based on the local asymptotic approximation has higher power than the likelihood‐ratio test based on the usual chi‐squared approximation. They examine the finite‐sample properties of the proposed intervals by means of a simulation study.     

The Two-Piece Normal-Laplace Distribution

This article considers the two-piece normal-Laplace (TPNL) distribution, a split skew distribution consisting of a normal part, and a Laplace part. The distribution is indexed by three parameters, representing location, scale, and shape. As illustrated with several examples, the TPNL family of distributions provides a useful alternative to other families of asymmetric distributions on the real line. However, because the likelihood function is not well behaved, standard theory of maximum-likelihood (ML) estimation does not apply to the TPNL family. In particular, the likelihood function can have multiple local maxima. We provide a procedure for computing ML estimators, and prove consistency and asymptotic normality of ML estimators, using non standard methods.     

On maximum likelihood estimation of the semi-parametric Cox model with time-varying covariates

Including time-varying covariates is a popular extension to the Cox model and a suitable approach for dealing with non-proportional hazards. However, partial likelihood (PL) estimation of this model has three shortcomings: (i) estimated regression coefficients can be less accurate in small samples with heavy censoring; (ii) the baseline hazard is not directly estimated and (iii) a covariance matrix for both the regression coefficients and the baseline hazard is not easily produced.We address these by developing a maximum likelihood (ML) approach to jointly estimate regression coefficients and baseline hazard using a constrained optimisation ensuring the latter''s non-negativity. We demonstrate asymptotic properties of these estimates and show via simulation their increased accuracy compared to PL estimates in small samples and show our method produces smoother baseline hazard estimates than the Breslow estimator.Finally, we apply our method to two examples, including an important real-world financial example to estimate time to default for retail home loans. We demonstrate using our ML estimate for the baseline hazard can give much clearer corroboratory evidence of the ‘humped hazard’, whereby the risk of loan default rises to a peak and then later falls.     

Approximate Bayesian Inference for Survival Models

Abstract. Bayesian analysis of time‐to‐event data, usually called survival analysis, has received increasing attention in the last years. In Cox‐type models it allows to use information from the full likelihood instead of from a partial likelihood, so that the baseline hazard function and the model parameters can be jointly estimated. In general, Bayesian methods permit a full and exact posterior inference for any parameter or predictive quantity of interest. On the other side, Bayesian inference often relies on Markov chain Monte Carlo (MCMC) techniques which, from the user point of view, may appear slow at delivering answers. In this article, we show how a new inferential tool named integrated nested Laplace approximations can be adapted and applied to many survival models making Bayesian analysis both fast and accurate without having to rely on MCMC‐based inference.     

Generalised quasi‐likelihood inference in a semi‐parametric binary dynamic mixed logit model

There exists a recent study where dynamic mixed‐effects regression models for count data have been extended to a semi‐parametric context. However, when one deals with other discrete data such as binary responses, the results based on count data models are not directly applicable. In this paper, we therefore begin with existing binary dynamic mixed models and generalise them to the semi‐parametric context. For inference, we use a new semi‐parametric conditional quasi‐likelihood (SCQL) approach for the estimation of the non‐parametric function involved in the semi‐parametric model, and a semi‐parametric generalised quasi‐likelihood (SGQL) approach for the estimation of the main regression, dynamic dependence and random effects variance parameters. A semi‐parametric maximum likelihood (SML) approach is also used as a comparison to the SGQL approach. The properties of the estimators are examined both asymptotically and empirically. More specifically, the consistency of the estimators is established and finite sample performances of the estimators are examined through an intensive simulation study.     

Exploring Parameter Relations for Multi‐Stage Models in Stage‐Wise Constant and Time Dependent Hazard Rates

Single cohort stage‐frequency data are considered when assessing the stage reached by individuals through destructive sampling. For this type of data, when all hazard rates are assumed constant and equal, Laplace transform methods have been applied in the past to estimate the parameters in each stage‐duration distribution and the overall hazard rates. If hazard rates are not all equal, estimating stage‐duration parameters using Laplace transform methods becomes complex. In this paper, two new models are proposed to estimate stage‐dependent maturation parameters using Laplace transform methods where non‐trivial hazard rates apply. The first model encompasses hazard rates that are constant within each stage but vary between stages. The second model encompasses time‐dependent hazard rates within stages. Moreover, this paper introduces a method for estimating the hazard rate in each stage for the stage‐wise constant hazard rates model. This work presents methods that could be used in specific types of laboratory studies, but the main motivation is to explore the relationships between stage maturation parameters that, in future work, could be exploited in applying Bayesian approaches. The application of the methodology in each model is evaluated using simulated data in order to illustrate the structure of these models.     

On Nonsmooth Estimating Functions via Jackknife Empirical Likelihood

In many applications, the parameters of interest are estimated by solving non‐smooth estimating functions with U‐statistic structure. Because the asymptotic covariances matrix of the estimator generally involves the underlying density function, resampling methods are often used to bypass the difficulty of non‐parametric density estimation. Despite its simplicity, the resultant‐covariance matrix estimator depends on the nature of resampling, and the method can be time‐consuming when the number of replications is large. Furthermore, the inferences are based on the normal approximation that may not be accurate for practical sample sizes. In this paper, we propose a jackknife empirical likelihood‐based inferential procedure for non‐smooth estimating functions. Standard chi‐square distributions are used to calculate the p‐value and to construct confidence intervals. Extensive simulation studies and two real examples are provided to illustrate its practical utilities.