Using threshold regression to analyze survival data from complex surveys: With application to mortality linked NHANES III Phase II genetic data.

The Cox proportional hazards (PH) model is a common statistical technique used for analyzing time-to-event data. The assumption of PH, however, is not always appropriate in real applications. In cases where the assumption is not tenable, threshold regression (TR) and other survival methods, which do not require the PH assumption, are available and widely used. These alternative methods generally assume that the study data constitute simple random samples. In particular, TR has not been studied in the setting of complex surveys that involve (1) differential selection probabilities of study subjects and (2) intracluster correlations induced by multistage cluster sampling. In this paper, we extend TR procedures to account for complex sampling designs. The pseudo-maximum likelihood estimation technique is applied to estimate the TR model parameters. Computationally efficient Taylor linearization variance estimators that consider both the intracluster correlation and the differential selection probabilities are developed. The proposed methods are evaluated by using simulation experiments with various complex designs and illustrated empirically by using mortality-linked Third National Health and Nutrition Examination Survey Phase II genetic data.

Analysis of counts with two latent classes, with application to risk assessment based on physician-visit records of cancer survivors.

Motivated by a cancer survivorship program, this paper explores event counts from two categories of individuals with unobservable membership. We formulate the counts using a latent class model and consider two likelihood-based inference procedures, the maximum likelihood estimation (MLE) and a pseudo-MLE procedure. The pseudo-MLE utilizes additional information on one of the latent classes. It yields reduced computational intensity and potentially increased estimation efficiency. We establish the consistency and asymptotic normality of the proposed pseudo-MLE, and we present an extended Huber sandwich estimator as a robust variance estimator for the pseudo-MLE. The finite-sample properties of the two-parameter estimators along with their variance estimators are examined by simulation. The proposed methodology is illustrated by physician-claim data from the cancer program.

Conditional modeling of longitudinal data with terminal event.

We consider a random effects model for longitudinal data with the occurrence of an informative terminal event that is subject to right censoring. Existing methods for analyzing such data include the joint modeling approach using latent frailty and the marginal estimating equation approach using inverse probability weighting; in both cases the effect of the terminal event on the response variable is not explicit and thus not easily interpreted. In contrast, we treat the terminal event time as a covariate in a conditional model for the longitudinal data, which provides a straight-forward interpretation while keeping the usual relationship of interest between the longitudinally measured response variable and covariates for times that are far from the terminal event. A two-stage semiparametric likelihood-based approach is proposed for estimating the regression parameters; first, the conditional distribution of the right-censored terminal event time given other covariates is estimated and then the likelihood function for the longitudinal event given the terminal event and other regression parameters is maximized. The method is illustrated by numerical simulations and by analyzing medical cost data for patients with end-stage renal disease. Desirable asymptotic properties are provided.

Two-Step Estimation of Models Between Latent Classes and External Variables.

We consider models which combine latent class measurement models for categorical latent variables with structural regression models for the relationships between the latent classes and observed explanatory and response variables. We propose a two-step method of estimating such models. In its first step, the measurement model is estimated alone, and in the second step the parameters of this measurement model are held fixed when the structural model is estimated. Simulation studies and applied examples suggest that the two-step method is an attractive alternative to existing one-step and three-step methods. We derive estimated standard errors for the two-step estimates of the structural model which account for the uncertainty from both steps of the estimation, and show how the method can be implemented in existing software for latent variable modelling.