This paper proposes a modelling 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 modelled using a parametric 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 are 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 disease onset age on the loss of visual acuity.
When facing multivariate covariates, general semiparametric regression techniques come at hand to propose flexible models that are unexposed to the curse of dimensionality. In this work a semiparametric copula-based estimator for conditional quantiles is investigated for complete or right-censored data. In spirit, the methodology is extending the recent work of Noh et al. (2013) and Noh et al. (2015), as the main idea consists in appropriately defining the quantile regression in terms of a multivariate copula and marginal distributions. Prior estimation of the latter and simple plug-in lead to…
In medical studies, the collected covariates usually contain underlying outliers. For clustered /longitudinal data with censored observations, the traditional Gehan-type estimator is robust to outliers existing in response but sensitive to outliers in the covariate domain, and it also ignores the within-cluster correlations. To take account of within-cluster correlations, varying cluster sizes, and outliers in covariates, we propose weighted Gehan-type estimating functions for parameter estimation in the accelerated failure time model for clustered data. We provide the asymptotic properties of…
A bivariate cure copula model with zero-inflated gamma frailty for right-censored data
Graduate Institute for Advanced Studies, SOKENDAI（SOKENDAI 高级研究研究生院）；Institute of Statistical Mathematics（统计数学研究所）；School of Informatics and Data Science, Hiroshima University（广岛大学信息科学与数据科学学院）
Copula modeling has gained much attention in many fields recently with the advantage of separating dependence structure from marginal distributions. In real data, however, serious ties are often present in one or multiple margins, which cause problems to many rank-based statistical methods developed under the assumption of continuous data with no ties. Simple methods such as breaking the ties at random or using average rank introduce independence into the data and, hence, lead to biased estimation. We propose an estimation method that treats the ranks of tied data as being interval censored an…
For the analysis of clustered survival data, two different types of models that take the association into account, are commonly used: frailty models and copula models. Frailty models assume that conditional on a frailty term for each cluster, the hazard functions of individuals within that cluster are independent. These unknown frailty terms with their imposed distribution are used to express the association between the different individuals in a cluster. Copula models on the other hand assume that the joint survival function of the individuals within a cluster is given by a copula function, e…
This paper extends the analysis of bivariate seemingly unrelated regression (SUR) Tobit model by modeling its nonlinear dependence structure through the Clayton copula. The ability in capturing/modeling the lower tail dependence of the SUR Tobit model where some data are censored (generally, at zero point) is an additionally useful feature of the Clayton copula. We propose a modified version of the inference function for margins (IFM) method (Joe and Xu, 1996), which we refer to as MIFM method, to obtain the estimates of the marginal parameters and a better (satisfactory) estimate of the copul…
In statistics, time-to-event analysis methods traditionally focus on the estimation of hazards. In recent years, machine learning methods have been proposed to directly predict the event times. We propose a method based on vine copula models to make point and interval predictions for a right-censored response variable given mixed discrete-continuous explanatory variables. Extensive experiments on simulated and real datasets show that our proposed vine copula approach provides a decent approximation to other time-to-event analysis models including Cox proportional hazards and Accelerate Failure…
We introduce a flexible individual frailty model for clustered right-censored data, in which covariate effects can be marginally interpreted as log failure odds ratios. Flexible correlation structures can be imposed by introducing multivariate exponential distributed frailties, constructed from a set of multivariate Gaussian random variables. Finite and infinite dimensional parameters are consistently estimated by maximizing a composite contributing marginal likelihood and a consistent estimate for their asymptotic covariance is proposed. Parameter estimation is implemented through a hybrid ex…
In many time-to-event studies, the event of interest is recurrent. Here, the data for each sample unit corresponds to a series of gap times between the subsequent events. Given a limited follow-up period, the last gap time might be right-censored. In contrast to classical analysis, gap times and censoring times cannot be assumed independent, i.e. the sequential nature of the data induces dependent censoring. Also, the recurrences typically vary between sample units leading to unbalanced data. To model the association pattern between gap times, so far only parametric margins combined with the r…
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 Arc…
A case-control family study is a study where individuals with a disease of interest (case probands) and individuals without the disease (control probands) are randomly sampled from a well-defined population. Possibly right-censored age at onset and disease status are observed for both probands and their relatives. Correlation among the outcomes within a family is induced by factors such as inherited genetic susceptibility, shared environment, and common behavior patterns. For this setting, we present a nonparametric estimator of the marginal survival function, based on local linear estimation …
A characteristic feature of time-to-event data analysis is possible censoring of the event time. Most of the statistical learning methods for handling censored data are limited by the assumption of independent censoring, even if this can lead to biased predictions when the assumption does not hold. This paper introduces Clayton-boost, a boosting approach built upon the accelerated failure time model, which uses a Clayton copula to handle the dependency between the event and censoring distributions. By taking advantage of a copula, the independent censoring assumption is not needed any more. Du…
A new method for clustered survival data]{A new method for clustered survival data: Estimation of treatment effect heterogeneity and variable selection
Data with uncertain, missing, censored, and correlated values are commonplace in many research fields including astronomy. Unfortunately, such data are often treated in an ad hoc way in the astronomical literature potentially resulting in inconsistent parameter estimates. Furthermore, in a realistic setting, the variables of interest or their errors may have non-normal distributions which complicates the modeling. I present a novel approach to compute the likelihood function for such data sets. This approach employs Gaussian copulas to decouple the correlation structure of variables and their …
Frequently, clinical trials and observational studies involve complex event history data with multiple events. When the observations are independent, the analysis of such studies can be based on standard methods for multi-state models. However, the independence assumption is often violated, such as in multicenter studies, which makes the use of standard methods improper. In this work we address the issue of nonparametric estimation and two-sample testing for the population-averaged transition and state occupation probabilities under general multi-state models based on right-censored, left-trun…
Since the inception of Bitcoin in 2008, cryptocurrencies have played an increasing role in the world of e-commerce, but the recent turbulence in the cryptocurrency market in 2018 has raised some concerns about their stability and associated risks. For investors, it is crucial to uncover the dependence relationships between cryptocurrencies for a more resilient portfolio diversification. Moreover, the stochastic behavior in both tails is important, as long positions are sensitive to a decrease in prices (lower tail), while short positions are sensitive to an increase in prices (upper tail). In …
