A semiparametric additive rates model for the weighted composite endpoint of recurrent and terminal events.

Recurrent event data with a terminal event commonly arise in longitudinal follow-up studies. We use a weighted composite endpoint of all recurrent and terminal events to assess the overall effects of covariates on the two types of events. A semiparametric additive rates model is proposed to analyze the weighted composite event process and the dependence structure among recurrent and terminal events is left unspecified. An estimating equation approach is developed for inference, and the asymptotic properties of the resulting estimators are established. The finite-sample behavior of the proposed estimators is evaluated through simulation studies, and an application to a bladder cancer study is illustrated.

A semiparametric additive rate model for a modulated renewal process.

Recurrent event data from a long single realization are widely encountered in point process applications. Modeling and analyzing such data are different from those for independent and identical short sequences, and the development of statistical methods requires careful consideration of the underlying dependence structure of the long single sequence. In this paper, we propose a semiparametric additive rate model for a modulated renewal process, and develop an estimating equation approach for the model parameters. The asymptotic properties of the resulting estimators are established by applying the limit theory for stationary mixing sequences. A block-based bootstrap procedure is presented for the variance estimation. Simulation studies are conducted to assess the finite-sample performance of the proposed estimators. An application to a data set from a cardiovascular mortality study is provided.

Additive mixed effect model for recurrent gap time data.

Gap times between recurrent events are often of primary interest in medical and observational studies. The additive hazards model, focusing on risk differences rather than risk ratios, has been widely used in practice. However, the marginal additive hazards model does not take the dependence among gap times into account. In this paper, we propose an additive mixed effect model to analyze gap time data, and the proposed model includes a subject-specific random effect to account for the dependence among the gap times. Estimating equation approaches are developed for parameter estimation, and the asymptotic properties of the resulting estimators are established. In addition, some graphical and numerical procedures are presented for model checking. The finite sample behavior of the proposed methods is evaluated through simulation studies, and an application to a data set from a clinic study on chronic granulomatous disease is provided.

Recent progresses in outcome-dependent sampling with failure time data.

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case-cohort design, generalized case-cohort design, stratified case-cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design.

Estimating effect of environmental contaminants on women's subfecundity for the MoBa study data with an outcome-dependent sampling scheme.

Motivated by the need from our on-going environmental study in the Norwegian Mother and Child Cohort (MoBa) study, we consider an outcome-dependent sampling (ODS) scheme for failure-time data with censoring. Like the case-cohort design, the ODS design enriches the observed sample by selectively including certain failure subjects. We present an estimated maximum semiparametric empirical likelihood estimation (EMSELE) under the proportional hazards model framework. The asymptotic properties of the proposed estimator were derived. Simulation studies were conducted to evaluate the small-sample performance of our proposed method. Our analyses show that the proposed estimator and design is more efficient than the current default approach and other competing approaches. Applying the proposed approach with the data set from the MoBa study, we found a significant effect of an environmental contaminant on fecundability.

Joint regression analysis of clustered current status data with latent variables.

Clustered current status data frequently occur in many fields of survival studies. Some potential factors related to the hazards of interest cannot be directly observed but are characterized through multiple correlated observable surrogates. In this article, we propose a joint modeling method for regression analysis of clustered current status data with latent variables and potentially informative cluster sizes. The proposed models consist of a factor analysis model to characterize latent variables through their multiple surrogates and an additive hazards frailty model to investigate covariate effects on the failure time and incorporate intra-cluster correlations. We develop an estimation procedure that combines the expectation-maximization algorithm and the weighted estimating equations. The consistency and asymptotic normality of the proposed estimators are established. The finite-sample performance of the proposed method is assessed via a series of simulation studies. This procedure is applied to analyze clustered current status data from the National Toxicology Program on a tumorigenicity study given by the United States Department of Health and Human Services.