Some recent developments for regression analysis of multivariate failure time data

Cox's seminal 1972 paper on regression methods for possibly censored failure time data popularized the use of time to an event as a primary response in prospective studies. But one key assumption of this and other regression methods is that observations are independent of one another. In many problems, failure times are clustered into small groups where outcomes within a group are correlated. Examples include failure times for two eyes from one person or for members of the same family.This paper presents a survey of models for multivariate failure time data. Two distinct classes of models are considered: frailty and marginal models. In a frailty model, the correlation is assumed to derive from latent variables (frailties) common to observations from the same cluster. Regression models are formulated for the conditional failure time distribution given the frailties. Alternatively, marginal models describe the marginal failure time distribution of each response while separately modelling the association among responses from the same cluster.We focus on recent extensions of the proportional hazards model for multivariate failure time data. Model formulation, parameter interpretation and estimation procedures are considered.     

Building marginal models for multiple ordinal measurements

Biomedical and psychosocial researchers increasingly utilize multiple indicators to assess an outcome of interest. We apply the ordinal estimating equations model for analysing this kind of measurement. We detail the special complexities of using this model to analyse clustered non-identical items and propose a workable model building strategy. Three graphical methods— cumulative log-odds, partial residual and Pearson residual plotting—are developed to diagnose the adequacy of models. The benefit of incorporating interitem associations and the trade-off between simple versus complex models are evaluated. Throughout the paper, an analysis to determine how measured impairments affect visual disability is used for illustration.     

A Diagnostic for Association in Bivariate Survival Models

We propose exploratory, easily implemented methods for diagnosing the appropriateness of an underlying copula model for bivariate failure time data, allowing censoring in either or both failure times. It is found that the proposed approach effectively distinguishes gamma from positive stable copula models when the sample is moderately large or the association is strong. Data from the Womens Health and Aging Study (WHAS, Guralnik et al., The Womenss Health and Aging Study: Health and Social Characterisitics of Older Women with Disability. National Institute on Aging: Bethesda, Mayland, 1995) are analyzed to demonstrate the proposed diagnostic methodology. The positive stable model gives a better overall fit to these data than the gamma frailty model, but it tends to underestimate association at the later time points. The finding is consistent with recent theory differentiating catastrophic from progressive disability onset in older adults. The proposed methods supply an interpretable quantity for copula diagnosis. We hope that they will usefully inform practitioners as to the reasonableness of their modeling choices.     

Adjusted variable plots for Cox's proportional hazards regression model

Adjusted variable plots are useful in linear regression for outlier detection and for qualitative evaluation of the fit of a model. In this paper, we extend adjusted variable plots to Cox's proportional hazards model for possibly censored survival data. We propose three different plots: a risk level adjusted variable (RLAV) plot in which each observation in each risk set appears, a subject level adjusted variable (SLAV) plot in which each subject is represented by one point, and an event level adjusted variable (ELAV) plot in which the entire risk set at each failure event is represented by a single point. The latter two plots are derived from the RLAV by combining multiple points. In each point, the regression coefficient and standard error from a Cox proportional hazards regression is obtained by a simple linear regression through the origin fit to the coordinates of the pictured points. The plots are illustrated with a reanalysis of a dataset of 65 patients with multiple myeloma.     

Parametric estimation of association in bivariate failure-time data subject to competing risks: sensitivity to underlying assumptions

Lifetime Data Analysis - There has arisen a considerable body of research addressing the estimation of association between paired failure times in the presence of competing risks. In a 2002 paper,...     

Semicompeting risks in aging research: methods,issues and needs

A semicompeting risks problem involves two-types of events: a nonterminal and a terminal event (death). Typically, the nonterminal event is the focus of the study, but the terminal event can preclude the occurrence of the nonterminal event. Semicompeting risks are ubiquitous in studies of aging. Examples of semicompeting risk dyads include: dementia and death, frailty syndrome and death, disability and death, and nursing home placement and death. Semicompeting risk models can be divided into two broad classes: models based only on observables quantities (class \(\mathcal {O}\) ) and those based on potential (latent) failure times (class \(\mathcal {L}\) ). The classical illness-death model belongs to class \(\mathcal {O}\) . This model is a special case of the multistate models, which has been an active area of methodology development. During the past decade and a half, there has also been a flurry of methodological activity on semicompeting risks based on latent failure times ( \(\mathcal {L}\) models). These advances notwithstanding, the semicompeting risks methodology has not penetrated biomedical research, in general, and gerontological research, in particular. Some possible reasons for this lack of uptake are: the methods are relatively new and sophisticated, conceptual problems associated with potential failure time models are difficult to overcome, paucity of expository articles aimed at educating practitioners, and non-availability of readily usable software. The main goals of this review article are: (i) to describe the major types of semicompeting risks problems arising in aging research, (ii) to provide a brief survey of the semicompeting risks methods, (iii) to suggest appropriate methods for addressing the problems in aging research, (iv) to highlight areas where more work is needed, and (v) to suggest ways to facilitate the uptake of the semicompeting risks methodology by the broader biomedical research community.