Marginal regression models with a time to event outcome and discrete multiple source predictors

Information from multiple informants is frequently used to assess psychopathology. We consider marginal regression models with multiple informants as discrete predictors and a time to event outcome. We fit these models to data from the Stirling County Study; specifically, the models predict mortality from self report of psychiatric disorders and also predict mortality from physician report of psychiatric disorders. Previously, Horton et al. found little relationship between self and physician reports of psychopathology, but that the relationship of self report of psychopathology with mortality was similar to that of physician report of psychopathology with mortality. Generalized estimating equations (GEE) have been used to fit marginal models with multiple informant covariates; here we develop a maximum likelihood (ML) approach and show how it relates to the GEE approach. In a simple setting using a saturated model, the ML approach can be constructed to provide estimates that match those found using GEE. We extend the ML technique to consider multiple informant predictors with missingness and compare the method to using inverse probability weighted (IPW) GEE. Our simulation study illustrates that IPW GEE loses little efficiency compared with ML in the presence of monotone missingness. Our example data has non-monotone missingness; in this case, ML offers a modest decrease in variance compared with IPW GEE, particularly for estimating covariates in the marginal models. In more general settings, e.g., categorical predictors and piecewise exponential models, the likelihood parameters from the ML technique do not have the same interpretation as the GEE. Thus, the GEE is recommended to fit marginal models for its flexibility, ease of interpretation and comparable efficiency to ML in the presence of missing data.     

Generalized Estimating Equations to Binary Probit Model

Inference in generalized linear mixed models with multivariate random effects is often made cumbersome by the high-dimensional intractable integrals involved in the marginal likelihood. This article presents an inferential methodology based on the generalized estimating equations for the probit latent traits models. This method belonging to the broad class of semi parametric approaches involves marginal joint moments of order 1 and 2, which has analytical expression. The different results are illustrated with a simulation study.     

The robustness of the quasilikelihood estimator

The quasilikelihood estimator is widely used in data analysis where a likelihood is not available. We illustrate that with a given variance function it is not only conservative, in minimizing a maximum risk, but also robust against a possible misspecification of either the likelihood or cumulants of the model. In examples it is compared with estimators based on maximum likelihood and quadratic estimating functions.     

Semiparametric estimation of treatment effect with density ratio model

In this study we propose a unified semiparametric approach to estimate various indices of treatment effect under the density ratio model, which connects two density functions by an exponential tilt. For each index, we construct two estimating functions based on the model and apply the generalized method of moments to improve the estimates. The estimating functions are allowed to be non smooth with respect to parameters and hence make the proposed method more flexible. We establish the asymptotic properties of the proposed estimators and illustrate the application with several simulations and two real data sets.     

EM algorithm-based likelihood estimation for a generalized Gompertz regression model in presence of survival data with long-term survivors: an application to uterine cervical cancer data

In this paper we develop a regression model for survival data in the presence of long-term survivors based on the generalized Gompertz distribution introduced by El-Gohary et al. [The generalized Gompertz distribution. Appl Math Model. 2013;37:13–24] in a defective version. This model includes as special case the Gompertz cure rate model proposed by Gieser et al. [Modelling cure rates using the Gompertz model with covariate information. Stat Med. 1998;17:831–839]. Next, an expectation maximization algorithm is then developed for determining the maximum likelihood estimates (MLEs) of the parameters of the model. In addition, we discuss the construction of confidence intervals for the parameters using the asymptotic distributions of the MLEs and the parametric bootstrap method, and assess their performance through a Monte Carlo simulation study. Finally, the proposed methodology was applied to a database on uterine cervical cancer.     

The sensitivity of estimates of the change in population behaviour to realistic changes in bias in repeated surveys

Summary.  The first British National Survey of Sexual Attitudes and Lifestyles (NATSAL) was conducted in 1990–1991 and the second in 1999–2001. When surveys are repeated, the changes in population parameters are of interest and are generally estimated from a comparison of the data between surveys. However, since all surveys may be subject to bias, such comparisons may partly reflect a change in bias. Typically limited external data are available to estimate the change in bias directly. However, one approach, which is often possible, is to define in each survey a sample of participants who are eligible for both surveys, and then to compare the reporting of selected events that occurred before the earlier survey time point. A difference in reporting suggests a change in overall survey bias between time points, although other explanations are possible. In NATSAL, changes in bias are likely to be similar for groups of sexual experiences. The grouping of experiences allows the information that is derived from the selected events to be incorporated into inference concerning population changes in other sexual experiences. We use generalized estimating equations, which incorporate weighting for differential probabilities of sampling and non-response in a relatively straightforward manner. The results, combined with estimates of the change in reporting, are used to derive minimum established population changes, based on NATSAL data. For some key population parameters, the change in reporting is seen to be consistent with a change in bias alone. Recommendations are made for the design of future surveys.     

A comparison of models for clustered binary outcomes: analysis of a designed immunology experiment

The lymphocyte proliferative assay (LPA) of immune competence was conducted on 52 subjects, with up to 36 processing conditions per subject, to evaluate whether samples could be shipped or stored overnight, rather than being processed on fresh blood as currently required. The LPA study resulted in clustered binary data, with both cluster level and cluster-varying covariates. Two modelling strategies for the analysis of such clustered binary data are through the cluster-specific and population-averaged approaches. Whereas most research in this area has focused on the analysis of matched pairs data, in many situations, such as the LPA study, cluster sizes are naturally larger. Through considerations of interpretation and efficiency of these models when applied to large clusters, the mixed effect cluster-specific model was selected as most appropriate for the analysis of the LPA data. The model confirmed that the LPA response is significantly impaired in individuals infected with the human immunodeficiency virus (HIV). The LPA response was found to be significantly lower for shipped and overnight samples than for fresh samples, and this effect was significantly stronger among HIV-infected individuals. Surprisingly, an anticoagulant effect was not detected.     

Numerical solution of likelihood equations for a first-order response surface model for mixture paired comparisons

Summary A simple procedure for numerical solution of the likelihood equations for estimating the regression parameters of a first-order response surface model for the treatment parameters of mixture paired comparison experiments is developed. It is demonstrated that, for defined rotatable designs, those regression parameters are simple functions of the main effect parameters of a corresponding factorial model with no interactions. The maximum likelihood estimators of those main effect parameters, and hence of their corresponding regression parameters, are obtained through using procedures of treatment contrasts, factorial and iterations. A numerical example is given to illustrate applications of the procedures developed in this paper.     

A generalized estimating equation approach to modelling foetal response in developmental toxicity studies when the number of implants is dose dependent

Summary. In developmental toxicity studies with exposure before implantation, the toxin that is used may interfere with the early reproductive process and prevent the implantation of some foetuses that would otherwise have been formed. A manifestation of this effect is a decreasing trend in the number of implants per dam as the dose level increases. Because unformed foetuses are not observable, Dunson proposed a multiple-imputation approach to estimate the number of missing foetuses. We propose instead to build a model for observable quantities only, namely the observed litter sizes and the observed numbers of deaths or malformations within litters. Using the probabilistic concept of thinning, we express the probability that a foetus fails to implant in terms of the parameters of the litter size distribution. Estimation is by means of generalized estimating equations and takes into account underdispersion of the observed litter sizes and overdispersion of the numbers of foetal deaths or malformations. A combined risk measure that takes into account not just post-implantation death or malformation but also the possibility of failure to implant is proposed and used to determine the virtually safe dose VSD. It is demonstrated numerically and graphically that ignoring the possibility of unformed foetuses leads to estimates of VSD that are too liberal. The proposed generalized estimating equation approach to estimating VSD and finding lower confidence limits is found to work well in a simulation study. We apply the proposed method to two data sets and compare the results that are obtained with those of existing studies.     

The pseudo‐GEE approach to the analysis of longitudinal surveys

Longitudinal surveys have emerged in recent years as an important data collection tool for population studies where the primary interest is to examine population changes over time at the individual level. Longitudinal data are often analyzed through the generalized estimating equations (GEE) approach. The vast majority of existing literature on the GEE method; however, is developed under non‐survey settings and are inappropriate for data collected through complex sampling designs. In this paper the authors develop a pseudo‐GEE approach for the analysis of survey data. They show that survey weights must and can be appropriately accounted in the GEE method under a joint randomization framework. The consistency of the resulting pseudo‐GEE estimators is established under the proposed framework. Linearization variance estimators are developed for the pseudo‐GEE estimators when the finite population sampling fractions are small or negligible, a scenario often held for large‐scale surveys. Finite sample performances of the proposed estimators are investigated through an extensive simulation study using data from the National Longitudinal Survey of Children and Youth. The results show that the pseudo‐GEE estimators and the linearization variance estimators perform well under several sampling designs and for both continuous and binary responses. The Canadian Journal of Statistics 38: 540–554; 2010 © 2010 Statistical Society of Canada