Search

Dynamic prediction uses patient information collected during follow-up to produce individualized survival predictions at given time points beyond treatment or diagnosis. This allows clinicians to obtain updated predictions of a patient's prognosis that can be used in making personalized treatment decisions. Two commonly used approaches for dynamic prediction are landmarking and joint modeling. Landmarking does not constitute a comprehensive probability model, and joint modeling often requires strong distributional assumptions and computationally intensive methods for estimation. We introduce an alternative approximate approach for dynamic prediction that aims to overcome the limitations of both methods while achieving good predictive performance. We separately specify the marker and failure time distributions conditional on surviving up to a prediction time of interest and use standard variable selection and goodness-of-fit techniques to identify the best-fitting models. Taking advantage of its analytic tractability and easy two-stage estimation, we use a Gaussian copula to link the marginal distributions smoothly at each prediction time with an association function. With simulation studies, we examine the proposed method's performance. We illustrate its use for dynamic prediction in an application to predicting death for heart valve transplant patients using longitudinal left ventricular mass index information. [ABSTRACT FROM AUTHOR]

This research is motivated by discovering and underpinning genetic causes for the progression of a bilateral eye disease, age-related macular degeneration (AMD), of which the primary outcomes, progression times to late-AMD, are bivariate and interval-censored due to intermittent assessment times. We propose a novel class of copula-based semiparametric transformation models for bivariate data under general interval censoring, which includes the case 1 interval censoring (current status data) and case 2 interval censoring. Specifically, the joint likelihood is modeled through a two-parameter Archimedean copula, which can flexibly characterize the dependence between the two margins in both tails. The marginal distributions are modeled through semiparametric transformation models using sieves, with the proportional hazards or odds model being a special case. We develop a computationally efficient sieve maximum likelihood estimation procedure for the unknown parameters, together with a generalized score test for the regression parameter(s). For the proposed sieve estimators of finite-dimensional parameters, we establish their asymptotic normality and efficiency. Extensive simulations are conducted to evaluate the performance of the proposed method in finite samples. Finally, we apply our method to a genome-wide analysis of AMD progression using the Age-Related Eye Disease Study data, to successfully identify novel risk variants associated with the disease progression. We also produce predicted joint and conditional progression-free probabilities, for patients with different genetic characteristics. [ABSTRACT FROM AUTHOR]

This article proposes a modeling strategy to infer the impact of a covariate on the dependence structure of right-censored clustered event time data. The joint survival function of the event times is modeled using a conditional copula whose parameter depends on a cluster-level covariate in a functional way. We use a local likelihood approach to estimate the form of the copula parameter and outline a generalized likelihood ratio-type test strategy to formally test its constancy. A bootstrap procedure is employed to obtain an approximate $p$-value for the test. The performance of the proposed estimation and testing methods is evaluated in simulations under different rates of right-censoring and for various parametric copula families, considering both parametrically and nonparametrically estimated margins. We apply the methods to data from the Diabetic Retinopathy Study to assess the impact of age at diabetes onset on the time to loss of visual acuity. [ABSTRACT FROM AUTHOR]

The heritability of chronic diseases can be effectively studied by examining the nature and extent of within-family associations in disease onset times. Families are typically accrued through a biased sampling scheme in which affected individuals are identified and sampled along with their relatives who may provide right-censored or current status data on their disease onset times. We develop likelihood and composite likelihood methods for modeling the within-family association in these times through copula models in which dependencies are characterized by Kendall's [Formula: see text] Auxiliary data from independent individuals are exploited by augmentating composite likelihoods to increase precision of marginal parameter estimates and consequently increase efficiency in dependence parameter estimation. An application to a motivating family study in psoriatic arthritis illustrates the method and provides some evidence of excessive paternal transmission of risk. [ABSTRACT FROM AUTHOR]

A copula-based model is described which enables joint analysis of multiple progressive multistate processes. Unlike intensity-based or frailty-based approaches to joint modeling, the copula formulation proposed herein ensures that a wide range of marginal multistate processes can be specified and the joint model will retain these marginal features. The copula formulation also facilitates a variety of approaches to estimation and inference including composite likelihood and two-stage estimation procedures. We consider processes with Markov margins in detail, which are often suitable when chronic diseases are progressive in nature. We give special attention to the setting in which individuals are examined intermittently and transition times are consequently interval-censored. Simulation studies give empirical insight into the different methods of analysis and an application involving progression in joint damage in psoriatic arthritis provides further illustration. [ABSTRACT FROM AUTHOR]

We discuss sample size determination for clinical trials evaluating the joint effects of an intervention on two potentially correlated co-primary time-to-event endpoints. For illustration, we consider the most common case, a comparison of two randomized groups, and use typical copula families to model the bivariate endpoints. A correlation structure of the bivariate logrank statistic is specified to account for the correlation among the endpoints, although the between-group comparison is performed using the univariate logrank statistic. We propose methods to calculate the required sample size to compare the two groups and evaluate the performance of the methods and the behavior of required sample sizes via simulation. [ABSTRACT FROM AUTHOR]

There are copula-based statistical models in the literature for regression with dependent data such as clustered and longitudinal overdispersed counts, for which parameter estimation and inference are straightforward. For situations where the main interest is in the regression and other univariate parameters and not the dependence, we propose a “weighted scores method”, which is based on weighting score functions of the univariate margins. The weight matrices are obtained initially fitting a discretized multivariate normal distribution, which admits a wide range of dependence. The general methodology is applied to negative binomial regression models. Asymptotic and small-sample efficiency calculations show that our method is robust and nearly as efficient as maximum likelihood for fully specified copula models. An illustrative example is given to show the use of our weighted scores method to analyze utilization of health care based on family characteristics. [ABSTRACT FROM PUBLISHER]