A comparison of nonparametric priors in hierarchical mixture modelling for AFT regression

We will pursue a Bayesian nonparametric approach in the hierarchical mixture modelling of lifetime data in two situations: density estimation, when the distribution is a mixture of parametric densities with a nonparametric mixing measure, and accelerated failure time (AFT) regression modelling, when the same type of mixture is used for the distribution of the error term. The Dirichlet process is a popular choice for the mixing measure, yielding a Dirichlet process mixture model for the error; as an alternative, we also allow the mixing measure to be equal to a normalized inverse-Gaussian prior, built from normalized inverse-Gaussian finite dimensional distributions, as recently proposed in the literature. Markov chain Monte Carlo techniques will be used to estimate the predictive distribution of the survival time, along with the posterior distribution of the regression parameters. A comparison between the two models will be carried out on the grounds of their predictive power and their ability to identify the number of components in a given mixture density.     

Copula-based regression models: A survey

In this review paper we collect several results about copula-based models, especially concerning regression models, by focusing on some insurance applications.     

A simple two-stage design for quantitative responses with application to a study in diabetic neuropathic pain

Two-stage designs offer substantial advantages for early phase II studies. The interim analysis following the first stage allows the study to be stopped for futility, or more positively, it might lead to early progression to the trials needed for late phase II and phase III. If the study is to continue to its second stage, then there is an opportunity for a revision of the total sample size. Two-stage designs have been implemented widely in oncology studies in which there is a single treatment arm and patient responses are binary. In this paper the case of two-arm comparative studies in which responses are quantitative is considered. This setting is common in therapeutic areas other than oncology. It will be assumed that observations are normally distributed, but that there is some doubt concerning their standard deviation, motivating the need for sample size review. The work reported has been motivated by a study in diabetic neuropathic pain, and the development of the design for that trial is described in detail.     

Models for the analysis of C-reactive protein in statin trials

Elevation in C-reactive protein (CRP) is an independent risk factor for cardiovascular disease progression and levels are reduced by treatment with statins. However, on-treatment CRP, given baseline CRP and treatment, is not normally distributed and outliers exist even when transformations are applied. Although classical non-parametric tests address some of these issues, they do not enable straightforward inclusion of covariate information. The aims of this study were to produce a model that improved efficiency and accuracy of analysis of CRP data. Estimation of treatment effects and identification of outliers were addressed using controlled trials of rosuvastatin. The robust statistical technique of MM-estimation was used to fit models to data in the presence of outliers and was compared with least-squares estimation. To develop the model, appropriate transformations of the response and baseline variables were selected. The model was used to investigate how on-treatment CRP related to baseline CRP and estimated treatment effects with rosuvastatin. On comparing least-squares and MM-estimation, MM-estimation was superior to least-squares estimation in that parameter estimates were more efficient and outliers were clearly identified. Relative reductions in CRP were higher at higher baseline CRP levels. There was also evidence of a dose-response relationship between CRP reductions from baseline and rosuvastatin. Several large outliers were identified, although there did not appear to be any relationships between the incidence of outliers and treatments. In conclusion, using robust estimation to model CRP data is superior to least-squares estimation and non-parametric tests in terms of efficiency, outlier identification and the ability to include covariate information.     

Missing item imputation for quality-of-life instruments with application to asthma quality-of-life questionnaires

There has been increasing use of quality-of-life (QoL) instruments in drug development. Missing item values often occur in QoL data. A common approach to solve this problem is to impute the missing values before scoring. Several imputation procedures, such as imputing with the most correlated item and imputing with a row/column model or an item response model, have been proposed. We examine these procedures using data from two clinical trials, in which the original asthma quality-of-life questionnaire (AQLQ) and the miniAQLQ were used. We propose two modifications to existing procedures: truncating the imputed values to eliminate outliers and using the proportional odds model as the item response model for imputation. We also propose a novel imputation method based on a semi-parametric beta regression so that the imputed value is always in the correct range and illustrate how this approach can easily be implemented in commonly used statistical software. To compare these approaches, we deleted 5% of item values in the data according to three different missingness mechanisms, imputed them using these approaches and compared the imputed values with the true values. Our comparison showed that the row/column-model-based imputation with truncation generally performed better, whereas our new approach had better performance under a number scenarios.     

Nonparametric estimation of waiting time distributions in a Markov model based on current status data

We construct nonparametric estimators of state waiting time distribution functions in a Markov multistate model using current status data. This is a particularly difficult problem since neither the entry nor the exit times of a given state are directly observed. These estimators are obtained, using the Markov property, from estimators of counting processes of state entry and exit times, as well as, the size of “at risk” sets of state entry and transitions out of that state. Consistency of our estimators is established. Finite-sample behavior of our estimators is studied by simulation, in which we show that our estimators based on current status data compare well with those based on complete data. We also illustrate our method using a pubertal development data set obtained from the NHANES III [1997. NHANES III Reference Manuals and Reports (CD-ROM). Analytic and Reporting Guidelines: The Third National Health and Nutrition Examination Survey (1988–94). National Center for Health Statistics, Centers for Disease Control and Prevention, Hyattsville, MD] study.     

A copula-based Markov chain model for the analysis of binary longitudinal data

A fully parametric first-order autoregressive (AR(1)) model is proposed to analyse binary longitudinal data. By using a discretized version of a copula, the modelling approach allows one to construct separate models for the marginal response and for the dependence between adjacent responses. In particular, the transition model that is focused on discretizes the Gaussian copula in such a way that the marginal is a Bernoulli distribution. A probit link is used to take into account concomitant information in the behaviour of the underlying marginal distribution. Fixed and time-varying covariates can be included in the model. The method is simple and is a natural extension of the AR(1) model for Gaussian series. Since the approach put forward is likelihood-based, it allows interpretations and inferences to be made that are not possible with semi-parametric approaches such as those based on generalized estimating equations. Data from a study designed to reduce the exposure of children to the sun are used to illustrate the methods.     

Forecast mean squared error reductionin the VAR(1) process

When VAR models are used to predict future outcomes, the forecast error can be substantial. Through imposition of restrictions on the off-diagonal elements of the parameter matrix, however, the information in the process may be condensed to the marginal processes. In particular, if the cross-autocorrelations in the system are small and only a small sample is available, then such a restriction may reduce the forecast mean squared error considerably.

In this paper, we propose three different techniques to decide whether to use the restricted or unrestricted model, i.e. the full VAR(1) model or only marginal AR(1) models. In a Monte Carlo simulation study, all three proposed tests have been found to behave quite differently depending on the parameter setting. One of the proposed tests stands out, however, as the preferred one and is shown to outperform other estimators for a wide range of parameter settings.     

Nonparametric estimation of the shape function in a Gamma process for degradation data

The author considers estimation under a Gamma process model for degradation data. The setting for degradation data is one in which n independent units, each with a Gamma process with a common shape function and scale parameter, are observed at several possibly different times. Covariates can be incorporated into the model by taking the scale parameter as a function of the covariates. The author proposes using the maximum pseudo‐likelihood method to estimate the unknown parameters. The method requires usage of the Pool Adjacent Violators Algorithm. Asymptotic properties, including consistency, convergence rate and asymptotic distribution, are established. Simulation studies are conducted to validate the method and its application is illustrated by using bridge beams data and carbon‐film resistors data. The Canadian Journal of Statistics 37: 102‐118; 2009 © 2009 Statistical Society of Canada     

Variance estimation when donor imputation is used to fill in missing values

Donor imputation is frequently used in surveys. However, very few variance estimation methods that take into account donor imputation have been developed in the literature. This is particularly true for surveys with high sampling fractions using nearest donor imputation, often called nearest‐neighbour imputation. In this paper, the authors develop a variance estimator for donor imputation based on the assumption that the imputed estimator of a domain total is approximately unbiased under an imputation model; that is, a model for the variable requiring imputation. Their variance estimator is valid, irrespective of the magnitude of the sampling fractions and the complexity of the donor imputation method, provided that the imputation model mean and variance are accurately estimated. They evaluate its performance in a simulation study and show that nonparametric estimation of the model mean and variance via smoothing splines brings robustness with respect to imputation model misspecifications. They also apply their variance estimator to real survey data when nearest‐neighbour imputation has been used to fill in the missing values. The Canadian Journal of Statistics 37: 400–416; 2009 © 2009 Statistical Society of Canada