The estimation of gross flows in the presence of measurement error using auxiliary variables

Classification error can lead to substantial biases in the estimation of gross flows from longitudinal data. We propose a method to adjust flow estimates for bias, based on fitting separate multinomial logistic models to the classification error probabilities and the true state transition probabilities using values of auxiliary variables. Our approach has the advantages that it does not require external information on misclassification rates, it permits the identification of factors that are related to misclassification and true transitions and it does not assume independence between classification errors at successive points in time. Constraining the prediction of the stocks to agree with the observed stocks protects against model misspecification. We apply the approach to data on women from the Panel Study of Income Dynamics with three categories of labour force status. The model fitted is shown to have interpretable coefficient estimates and to provide a good fit. Simulation results indicate good performance of the model in predicting the true flows and robustness against departures from the model postulated.     

Flexible semi-parametric regression of state occupational probabilities in a multistate model with right-censored data

Inference for the state occupation probabilities, given a set of baseline covariates, is an important problem in survival analysis and time to event multistate data. We introduce an inverse censoring probability re-weighted semi-parametric single index model based approach to estimate conditional state occupation probabilities of a given individual in a multistate model under right-censoring. Besides obtaining a temporal regression function, we also test the potential time varying effect of a baseline covariate on future state occupation. We show that the proposed technique has desirable finite sample performances and its performance is competitive when compared with three other existing approaches. We illustrate the proposed methodology using two different data sets. First, we re-examine a well-known data set dealing with leukemia patients undergoing bone marrow transplant with various state transitions. Our second illustration is based on data from a study involving functional status of a set of spinal cord injured patients undergoing a rehabilitation program.     

Latent class models for longitudinal studies of the elderly with data missing at random

The elderly population in the USA is expected to double in size by the year 2025, making longitudinal health studies of this population of increasing importance. The degree of loss to follow-up in studies of the elderly, which is often because elderly people cannot remain in the study, enter a nursing home or die, make longitudinal studies of this population problematic. We propose a latent class model for analysing multiple longitudinal binary health outcomes with multiple-cause non-response when the data are missing at random and a non-likelihood-based analysis is performed. We extend the estimating equations approach of Robins and co-workers to latent class models by reweighting the multiple binary longitudinal outcomes by the inverse probability of being observed. This results in consistent parameter estimates when the probability of non-response depends on observed outcomes and covariates (missing at random) assuming that the model for non-response is correctly specified. We extend the non-response model so that institutionalization, death and missingness due to failure to locate, refusal or incomplete data each have their own set of non-response probabilities. Robust variance estimates are derived which account for the use of a possibly misspecified covariance matrix, estimation of missing data weights and estimation of latent class measurement parameters. This approach is then applied to a study of lower body function among a subsample of the elderly participating in the 6-year Longitudinal Study of Aging.     

A continuous-time Markov chain approach with the analytic likelihood in studies of behavioral changes

Abstract

We develop an analytic likelihood approach for a four-state CTMC by solving the backwards Kolmogorov differential equations, reducing this bias in transition rate estimates. A simulation study is performed to assess the performance of this new method and confirms that it achieves good coverage probabilities with low bias and standard errors. Finally, we analyzed data from Project SUCCESS to estimate the study each participant’s transitions among behavioral stage, consisting of risky drinking and possible ineffective using of contraception, which comprise the primary endpoint of risk of an alcohol-exposed pregnancy.     

Failure time studies with intermittent observation and losses to follow-up

In health research interest often lies in modeling a failure time process but in many cohort studies failure status is only determined at scheduled assessment times. While the assessment times may be fixed upon study entry, individuals may become lost to follow-up and miss visits subsequent to the time of loss to follow-up. We consider a three-state model to characterize a joint failure and loss to follow-up process, and use it to investigate the impact of dependent loss to follow-up on standard parametric, nonparametric, and semiparametric analysis. The effect of dependent loss to follow-up is mitigated by fitting the joint model. The performance of standard methods is studied using the asymptotic theory of misspecified models, and the finite sample performance is examined for the standard and joint analyses through simulation studies. An application to data from a youth smoking prevention study is presented for illustration.     

Semiparametric log-linear regression for longitudinal measurements subject to outcome-dependent follow-up

A common problem for longitudinal data analyses is that subjects follow-up is irregular, often related to the past outcome or other factors associated with the outcome measure that are not included in the regression model. Analyses unadjusted for outcome-dependent follow-up yield biased estimates. We propose a longitudinal data analysis that can provide consistent estimates in regression models that are subject to outcome-dependent follow-up. We focus on semiparametric marginal log-link regression with arbitrary unspecified baseline function. Based on estimating equations, the proposed class of estimators are root n consistent and asymptotically normal. We present simulation studies that assess the performance of the estimators under finite samples. We illustrate our approach using data from a health services research study.     

Prediction of disease status: A regressive model approach for repeated measures

In this paper, regressive models are proposed for modeling a sequence of transitions in longitudinal data. These models are employed to predict the future status of the outcome variable of the individuals on the basis of their underlying background characteristics or risk factors. The estimation of parameters and also estimates of conditional and unconditional probabilities are shown for repeated measures. The goodness of fit tests are extended in this paper on the basis of the deviance and the Hosmer–Lemeshow procedures and generalized to repeated measures. In addition, to measure the suitability of the proposed models for predicting the disease status, we have extended the ROC curve approach to repeated measures. The procedure is shown for the conditional models for any order as well as for the unconditional model, to predict the outcome at the end of the study. The test procedures are also suggested. For testing the differences between areas under the ROC curves in subsequent follow-ups, two different test procedures are employed, one of which is based on permutation test. In this paper, an unconditional model is proposed on the basis of conditional models for the disease progression of depression among the elderly population in the USA on the basis of the Health and Retirement Survey data collected longitudinally. The illustration shows that the disease progression observed conditionally can be employed to predict the outcome and the role of selected variables and the previous outcomes can be utilized for predictive purposes. The results show that the percentage of correct predictions of a disease is quite high and the measures of sensitivity and specificity are also reasonably impressive. The extended measures of area under the ROC curve show that the models provide a reasonably good fit in terms of predicting the disease status during a long period of time. This procedure will have extensive applications in the field of longitudinal data analysis where the objective is to obtain estimates of unconditional probabilities on the basis of series of conditional transitional models.     

A Bayesian Approach in Estimating Transition Probabilities of a Discrete-time Markov Chain for Ignorable Intermittent Missing Data

This article focuses on data analyses under the scenario of missing at random within discrete-time Markov chain models. The naive method, nonlinear (NL) method, and Expectation-Maximization (EM) algorithm are discussed. We extend the NL method into a Bayesian framework, using an adjusted rejection algorithm to sample the posterior distribution, and estimating the transition probabilities with a Monte Carlo algorithm. We compare the Bayesian nonlinear (BNL) method with the naive method and the EM algorithm with various missing rates, and comprehensively evaluate estimators in terms of biases, variances, mean square errors, and coverage probabilities (CPs). Our simulation results show that the EM algorithm usually offers smallest variances but with poorest CP, while the BNL method has smaller variances and better/similar CP as compared to the naive method. When the missing rate is low (about 9%, MAR), the three methods are comparable. Whereas when the missing rate is high (about 25%, MAR), overall, the BNL method performs slightly but consistently better than the naive method regarding variances and CP. Data from a longitudinal study of stress level among caregivers of individuals with Alzheimer’s disease is used to illustrate these methods.     

Prior distributions for stratified capture-recapture models

We consider the Arnason-Schwarz model, usually used to estimate survival and movement probabilities from capture-recapture data. A missing data structure of this model is constructed which allows a clear separation of information relative to capture and relative to movement. Extensions of the Arnason-Schwarz model are considered. For example, we consider a model that takes into account both the individual migration history and the individual reproduction history. Biological assumptions of these extensions are summarized via a directed graph. Owing to missing data, the posterior distribution of parameters is numerically intractable. To overcome those computational difficulties we advocate a Gibbs sampling algorithm that takes advantage of the missing data structure inherent in capture-recapture models. Prior information on survival, capture and movement probabilities typically consists of a prior mean and of a prior 95% credible confidence interval. Dirichlet distributions are used to incorporate some prior information on capture, survival probabilities, and movement probabilities. Finally, the influence of the prior on the Bayesian estimates of movement probabilities is examined.     

Prior distributions for stratified capture-recapture models

We consider the Arnason-Schwarz model, usually used to estimate survival and movement probabilities from capture-recapture data. A missing data structure of this model is constructed which allows a clear separation of information relative to capture and relative to movement. Extensions of the Arnason-Schwarz model are considered. For example, we consider a model that takes into account both the individual migration history and the individual reproduction history. Biological assumptions of these extensions are summarized via a directed graph. Owing to missing data, the posterior distribution of parameters is numerically intractable. To overcome those computational difficulties we advocate a Gibbs sampling algorithm that takes advantage of the missing data structure inherent in capture-recapture models. Prior information on survival, capture and movement probabilities typically consists of a prior mean and of a prior 95% credible confidence interval. Dirichlet distributions are used to incorporate some prior information on capture, survival probabilities, and movement probabilities. Finally, the influence of the prior on the Bayesian estimates of movement probabilities is examined.     

Joint analysis of nonlinear heterogeneous longitudinal data and binary outcome: an application to AIDS clinical studies

Finite mixture models are currently used to analyze heterogeneous longitudinal data. By releasing the homogeneity restriction of nonlinear mixed-effects (NLME) models, finite mixture models not only can estimate model parameters but also cluster individuals into one of the pre-specified classes with class membership probabilities. This clustering may have clinical significance, which might be associated with a clinically important binary outcome. This article develops a joint modeling of a finite mixture of NLME models for longitudinal data in the presence of covariate measurement errors and a logistic regression for a binary outcome, linked by individual latent class indicators, under a Bayesian framework. Simulation studies are conducted to assess the performance of the proposed joint model and a naive two-step model, in which finite mixture model and logistic regression are fitted separately, followed by an application to a real data set from an AIDS clinical trial, in which the viral dynamics and dichotomized time to the first decline of CD4/CD8 ratio are analyzed jointly.     

A three-state continuous time Markov chain model for HIV disease burden

Plasma HIV viral load (VL) is the clinical indicator used to evaluate disease burden for HIV-infected patients. We developed a covariate-adjusted, three-state, homogenous continuous time Markov chain model for HIV/AIDS disease burden among subgroups. We defined Detectable and Undetectable HIV VL levels as two transient states and Death as the third absorbing state. We implemented the exact maximum likelihood method to estimate the parameters with related asymptotic distribution to conduct hypothesis testing. We evaluated the proposed model using HIV-infected individuals from South Carolina (SC) HIV surveillance data. Using the developed model, we estimated and compared the transition hazards, transition probabilities, and the state-specific duration for HIV-infected individuals. We examined gender, race/ethnicity, age, CD4 count, place of residence, and antiretroviral treatment regimen prescribed at the beginning of the study period. We found that patients with a higher CD4 count, increased age, heterosexual orientation, white, and single tablet regimen users were associated with reduced risk of transitioning to a Detectable VL from an Undetectable VL, whereas shorter time since diagnosis, being male, and injection drug use increased the risk of the same transition.     

Zero-Inflated Poisson Regression for Longitudinal Data

Medical and public health research often involve the analysis of repeated or longitudinal count data that exhibit excess zeros such as the number of yearly doctor visits by a group of individuals over a number of years. Zero-inflated Poisson (ZIP) regression models can be used to account for excess zeros in count data. We propose an extension of the ZIP model that is appropriate for longitudinal data. Our extension includes a non stationary, observation-driven time series model based correlation structure. We discuss estimation of the model parameters and the inefficiency of the estimators when the correlation structure is mis-specified. The model's application to the analysis of health care utilization data is also discussed.     

Inference in Semi‐Parametric Dynamic Models for Repeated Count Data

This paper deals with a longitudinal semi‐parametric regression model in a generalised linear model setup for repeated count data collected from a large number of independent individuals. To accommodate the longitudinal correlations, we consider a dynamic model for repeated counts which has decaying auto‐correlations as the time lag increases between the repeated responses. The semi‐parametric regression function involved in the model contains a specified regression function in some suitable time‐dependent covariates and a non‐parametric function in some other time‐dependent covariates. As far as the inference is concerned, because the non‐parametric function is of secondary interest, we estimate this function consistently using the independence assumption‐based well‐known quasi‐likelihood approach. Next, the proposed longitudinal correlation structure and the estimate of the non‐parametric function are used to develop a semi‐parametric generalised quasi‐likelihood approach for consistent and efficient estimation of the regression effects in the parametric regression function. The finite sample performance of the proposed estimation approach is examined through an intensive simulation study based on both large and small samples. Both balanced and unbalanced cluster sizes are incorporated in the simulation study. The asymptotic performances of the estimators are given. The estimation methodology is illustrated by reanalysing the well‐known health care utilisation data consisting of counts of yearly visits to a physician by 180 individuals for four years and several important primary and secondary covariates.     

Empirical likelihood for parameters in an additive partially linear errors-in-variables model with longitudinal data

Empirical likelihood inferences for the parameter component in an additive partially linear errors-in-variables model with longitudinal data are investigated in this article. A corrected-attenuation block empirical likelihood procedure is used to estimate the regression coefficients, a corrected-attenuation block empirical log-likelihood ratio statistic is suggested and its asymptotic distribution is obtained. Compared with the method based on normal approximations, our proposed method does not require any consistent estimator for the asymptotic variance and bias. Simulation studies indicate that our proposed method performs better than the method based on normal approximations in terms of relatively higher coverage probabilities and smaller confidence regions. Furthermore, an example of an air pollution and health data set is used to illustrate the performance of the proposed method.     

Generalised Linear Models Incorporating Population Level Information: An Empirical Likelihood Based Approach

In many situations information from a sample of individuals can be supplemented by population level information on the relationship between a dependent variable and explanatory variables. Inclusion of the population level information can reduce bias and increase the efficiency of the parameter estimates.Population level information can be incorporated via constraints on functions of the model parameters. In general the constraints are nonlinear making the task of maximum likelihood estimation harder. In this paper we develop an alternative approach exploiting the notion of an empirical likelihood. It is shown that within the framework of generalised linear models, the population level information corresponds to linear constraints, which are comparatively easy to handle. We provide a two-step algorithm that produces parameter estimates using only unconstrained estimation. We also provide computable expressions for the standard errors. We give an application to demographic hazard modelling by combining panel survey data with birth registration data to estimate annual birth probabilities by parity.     

Prediction of transplant-free survival in idiopathic pulmonary fibrosis patients using joint models for event times and mixed multivariate longitudinal data

We implement a joint model for mixed multivariate longitudinal measurements, applied to the prediction of time until lung transplant or death in idiopathic pulmonary fibrosis. Specifically, we formulate a unified Bayesian joint model for the mixed longitudinal responses and time-to-event outcomes. For the longitudinal model of continuous and binary responses, we investigate multivariate generalized linear mixed models using shared random effects. Longitudinal and time-to-event data are assumed to be independent conditional on available covariates and shared parameters. A Markov chain Monte Carlo algorithm, implemented in OpenBUGS, is used for parameter estimation. To illustrate practical considerations in choosing a final model, we fit 37 different candidate models using all possible combinations of random effects and employ a deviance information criterion to select a best-fitting model. We demonstrate the prediction of future event probabilities within a fixed time interval for patients utilizing baseline data, post-baseline longitudinal responses, and the time-to-event outcome. The performance of our joint model is also evaluated in simulation studies.     

Estimating the prevalence of male clients of prostitute women in Vancouver with a simple capture–recapture method

Summary.  Capture–recapture techniques are widely used to estimate the size of difficult-to-count human populations. Applications often focus on the overlap between two or more samples, but another type of data that is encountered in human studies involves only the number of times that particular individuals were encountered in the study period. We present a method for estimating the population size in this situation. This method is simple and technically accessible and allows for entries and exits by individuals and for a difference between probabilities of initial and subsequent contacts. We apply the method to arrest data on male clients of prostitute women in Vancouver.     

Slope Estimation for Bivariate Longitudinal Outcomes Adjusting for Informative Right Censoring Using Discrete Survival Model: Application to the Renal Transplant Cohort

Patients undergoing renal transplantation are prone to graft failure which causes lost of follow-up measures on their blood urea nitrogen and serum creatinine levels. These two outcomes are measured repeatedly over time to assess renal function following transplantation. Loss of follow-up on these bivariate measures results in informative right censoring, a common problem in longitudinal data that should be adjusted for so that valid estimates are obtained. In this study, we propose a bivariate model that jointly models these two longitudinal correlated outcomes and generates population and individual slopes adjusting for informative right censoring using a discrete survival approach. The proposed approach is applied to the clinical dataset of patients who had undergone renal transplantation. A simulation study validates the effectiveness of the approach.     

Bias in transition-specific survival and movement probabilities estimated using capture-recapture data

Transition probabilities can be estimated when capture-recapture data are available from each stratum on every capture occasion using a conditional likelihood approach with the Arnason-Schwarz model. To decompose the fundamental transition probabilities into derived parameters, all movement probabilities must sum to 1 and all individuals in stratum r at time i must have the same probability of survival regardless of which stratum the individual is in at time i + 1. If movement occurs among strata at the end of a sampling interval, survival rates of individuals from the same stratum are likely to be equal. However, if movement occurs between sampling periods and survival rates of individuals from the same stratum are not the same, estimates of stratum survival can be confounded with estimates of movement causing both estimates to be biased. Monte Carlo simulations were made of a three-sample model for a population with two strata using SURVIV. When differences were created in transition-specific survival rates for survival rates from the same stratum, relative bias was <2% in estimates of stratum survival and capture rates but relative bias in movement rates was much higher and varied. The magnitude of the relative bias in the movement estimate depended on the relative difference between the transition-specific survival rates and the corresponding stratum survival rate. The direction of the bias in movement rate estimates was opposite to the direction of this difference. Increases in relative bias due to increasing heterogeneity in probabilities of survival, movement and capture were small except when survival and capture probabilities were positively correlated within individuals.