Choice of Parametric Accelerated Life and Proportional Hazards Models for Survival Data: Asymptotic Results

We discuss the impact of misspecifying fully parametric proportional hazards and accelerated life models. For the uncensored case, misspecified accelerated life models give asymptotically unbiased estimates of covariate effect, but the shape and scale parameters depend on the misspecification. The covariate, shape and scale parameters differ in the censored case. Parametric proportional hazards models do not have a sound justification for general use: estimates from misspecified models can be very biased, and misleading results for the shape of the hazard function can arise. Misspecified survival functions are more biased at the extremes than the centre. Asymptotic and first order results are compared. If a model is misspecified, the size of Wald tests will be underestimated. Use of the sandwich estimator of standard error gives tests of the correct size, but misspecification leads to a loss of power. Accelerated life models are more robust to misspecification because of their log-linear form. In preliminary data analysis, practitioners should investigate proportional hazards and accelerated life models; software is readily available for several such models.     

Chi-Squared Goodness-of-Fit Tests for Parametric Accelerated Failure Time Models

We give chi-squared goodness-of fit tests for parametric regression models such as accelerated failure time, proportional hazards, generalized proportional hazards, frailty models, transformation models, and models with cross-effects of survival functions. Random right censored data are used. Choice of random grouping intervals as data functions is considered.     

A Semiparametric Approach for Accelerated Failure Time Models with Covariates Subject to Measurement Error

There are relatively few discussions about measurement error in the accelerated failure time (AFT) model, particularly for the semiparametric AFT model. In this article, we propose an adjusted estimation procedure for the semiparametric AFT model with covariates subject to measurement error, based on the profile likelihood approach and simulation and exploration (SIMEX) method. The simulation studies show that the proposed semiparametric SIMEX approach performs well. The proposed approach is applied to a coronary heart disease dataset from the Busselton Health study for illustration.     

Proportional Hazards Model for Multivariate Failure Time Data

Multivariate failure time data also referred to as correlated or clustered failure time data, often arise in survival studies when each study subject may experience multiple events. Statistical analysis of such data needs to account for intracluster dependence. In this article, we consider a bivariate proportional hazards model using vector hazard rate, in which the covariates under study have different effect on two components of the vector hazard rate function. Estimation of the parameters as well as base line hazard function are discussed. Properties of the estimators are investigated. We illustrated the method using two real life data. A simulation study is reported to assess the performance of the estimator.     

Robust Smoothed Rank Estimation Methods for Accelerated Failure Time Model Allowing Clusters

Smoothed Gehan rank estimation methods are widely used in accelerated failure time (AFT) models with/without clusters. However, most methods are sensitive to outliers in the covariates. In order to solve this problem, we propose robust approaches based on the smoothed Gehan rank estimation methods for the AFT model, allowing for clusters by employing two different weight functions. Simulation studies show that the proposed methods outperform existing smoothed rank estimation methods regarding their biases and standard deviations when there are outliers in the covariates. The proposed methods are also applied to a real dataset from the “Major cardiovascular interventions” study.     

Accelerated Recurrence Time Models

Abstract.  For the analysis with recurrent events, we propose a generalization of the accelerated failure time model to allow for evolving covariate effects. These so-called accelerated recurrence time models postulate that the time to expected recurrence frequency, upon transformation, is a linear function of covariates with frequency-dependent coefficients. This modelling strategy shares the same spirit as quantile regression. An estimation and inference procedure is developed by generalizing the celebrated Powell's ( J. Econometrics 25, 1984, 303; J. Econometrics 32, 1986, 143) estimator for censored quantile regression. Consistency and asymptotic normality of the proposed estimator are established. An algorithm is devised to attain good computational efficiency. Simulations demonstrate that this proposal performs well under practical settings. This methodology is illustrated in an application to the well-known bladder cancer study.     

Testing Goodness of Fit of Parametric AFT and PH Models with Residuals

In this article, we consider the problems of testing the goodness of fit of the parametric accelerated failure time model and the Cox proportional hazards model. We consider omnibus test statistics based on residuals. The statistical distributions of Kolmogorov, Cramer-von Mises–Smirnov, and Anderson–Darling statistics are all investigated by means of Monte Carlo simulations. Type-I, Type-II, and independent random censoring situations are all considered in this study. A Monte Carlo power study has also been carried out for these tests to distinguish between various baseline models, which reveals that the Anderson–Darling test performs better than the others.     

An Alternative Estimation Method for the Semiparametric Accelerated Failure Time Mixture Cure Model

We propose an alternative estimation method for the semiparametric accelerated failure time mixture cure model by incorporating the profile likelihood into the M-step of the EM algorithm. The proposed method performs as well as the existing methods when the censoring is light and better than the existing methods when the censoring is moderate from the simulation studies. Regarding to the computational time, the proposed method runs faster than the existing methods.     

Bayesian Model Selection and Averaging in Additive and Proportional Hazards Models

Although Cox proportional hazards regression is the default analysis for time to event data, there is typically uncertainty about whether the effects of a predictor are more appropriately characterized by a multiplicative or additive model. To accommodate this uncertainty, we place a model selection prior on the coefficients in an additive-multiplicative hazards model. This prior assigns positive probability, not only to the model that has both additive and multiplicative effects for each predictor, but also to sub-models corresponding to no association, to only additive effects, and to only proportional effects. The additive component of the model is constrained to ensure non-negative hazards, a condition often violated by current methods. After augmenting the data with Poisson latent variables, the prior is conditionally conjugate, and posterior computation can proceed via an efficient Gibbs sampling algorithm. Simulation study results are presented, and the methodology is illustrated using data from the Framingham heart study.     

The Influence of Random Effects on Univariate and Bivariate Discrete Proportional Hazards Models

The random effects survival model has been widely used in the recent literature as a generalization of the continuous proportional hazards model. When a random effect is present, it is known that the hazard rates are generally underestimated in the context of continuous proportional hazards models. This article establishes theorems for the influence of random effects on both univariate and bivariate discrete proportional hazards models.     

Estimating Marginal Effects in Accelerated Failure Time Models for Serial Sojourn Times Among Repeated Events

Recurrent event data are commonly encountered in longitudinal studies when events occur repeatedly over time for each study subject. An accelerated failure time (AFT) model on the sojourn time between recurrent events is considered in this article. This model assumes that the covariate effect and the subject-specific frailty are additive on the logarithm of sojourn time, and the covariate effect maintains the same over distinct episodes, while the distributions of the frailty and the random error in the model are unspecified. With the ordinal nature of recurrent events, two scale transformations of the sojourn times are derived to construct semiparametric methods of log-rank type for estimating the marginal covariate effects in the model. The proposed estimation approaches/inference procedures also can be extended to the bivariate events, which alternate themselves over time. Examples and comparisons are presented to illustrate the performance of the proposed methods.     

Alternative Time Scales and Failure Time Models

In many reliability applications, there may not be a unique plausible scale in which to measure time to failure or assess performance. This is especially the case when several measures of usage are available on each unit. For example, the age, the total number of flight hours, and the number of landings are usage measures that are often considered important in aircraft reliability. Similarly, in medical or biological applications of survival analysis there are often alternative scales (e.g., Oakes, 1995). This paper considers the definition of a "good" time scale, along with methods of determining a time scale.     

Causal Proportional Hazards Models and Time-constant Exposure in Randomized Clinical Trials

The last decade saw enormous progress in the development of causal inference tools to account for noncompliance in randomized clinical trials. With survival outcomes, structural accelerated failure time (SAFT) models enable causal estimation of effects of observed treatments without making direct assumptions on the compliance selection mechanism. The traditional proportional hazards model has however rarely been used for causal inference. The estimator proposed by Loeys and Goetghebeur (2003, Biometrics vol. 59 pp. 100–105) is limited to the setting of all or nothing exposure. In this paper, we propose an estimation procedure for more general causal proportional hazards models linking the distribution of potential treatment-free survival times to the distribution of observed survival times via observed (time-constant) exposures. Specifically, we first build models for observed exposure-specific survival times. Next, using the proposed causal proportional hazards model, the exposure-specific survival distributions are backtransformed to their treatment-free counterparts, to obtain – after proper mixing – the unconditional treatment-free survival distribution. Estimation of the parameter(s) in the causal model is then based on minimizing a test statistic for equality in backtransformed survival distributions between randomized arms.     

Choice of parametric models in survival analysis: applications to monotherapy for epilepsy and cerebral palsy

Summary. In the analysis of medical survival data, semiparametric proportional hazards models are widely used. When the proportional hazards assumption is not tenable, these models will not be suitable. Other models for covariate effects can be useful. In particular, we consider accelerated life models, in which the effect of covariates is to scale the quantiles of the base-line distribution. Solomon and Hutton have suggested that there is some robustness to misspecification of survival regression models. They showed that the relative importance of covariates is preserved under misspecification with assumptions of small coefficients and orthogonal transformation of covariates. We elucidate these results by applications to data from five trials which compare two common anti-epileptic drugs (carbamazepine versus sodium valporate monotherapy for epilepsy) and to survival of a cohort of people with cerebral palsy. Results on the robustness against model misspecification depend on the assumptions of small coefficients and on the underlying distribution of the data. These results hold in cerebral palsy but do not hold in epilepsy data which have early high hazard rates. The orthogonality of coefficients is not important. However, the choice of model is important for an estimation of the magnitude of effects, particularly if the base-line shape parameter indicates high initial hazard rates.     

Power-Law Adjusted Survival Models

A simple adjustment to parametric failure-time distributions, which allows for much greater flexibility in the shape of the hazard-rate function, is considered. Analytical expressions for the distributions of the power-law adjusted Weibull, gamma, log-gamma, generalized gamma, lognormal, and Pareto distributions are given. Most of these allow for bathtub-shaped and other multi-modal forms of the hazard rate. The new distributions are fitted to real failure-time data which exhibit a multi-modal hazard-rate function and the fits are compared.     

Methods for Bivariate Survival Data with Mismeasured Covariates Under an Accelerated Failure Time Model

Accelerated failure time models are useful in survival data analysis, but such models have received little attention in the context of measurement error. In this paper we discuss an accelerated failure time model for bivariate survival data with covariates subject to measurement error. In particular, methods based on the marginal and joint models are considered. Consistency and efficiency of the resultant estimators are investigated. Simulation studies are carried out to evaluate the performance of the estimators as well as the impact of ignoring the measurement error of covariates. As an illustration we apply the proposed methods to analyze a data set arising from the Busselton Health Study (Knuiman et al., 1994 Knuiman , M. W. , Cullent , K. J. , Bulsara , M. K. , Welborn , T. A. , Hobbs , M. S. T. ( 1994 ). Mortality trends, 1965 to 1989, in Busselton, the site of repeated health surveys and interventions . Austral. J. Public Health 18 : 129 – 135 . [CSA] [Crossref], [PubMed] , [Google Scholar]).     

Marginal Analysis For Clustered Failure Time Data

Clustered failure time data are commonly encountered in biomedical research where the study subjects from the same cluster (e.g., family) share the common genetic and/or environmental factors such that the failure times within the same cluster are correlated. Two approaches that are commonly used to account for the intra-cluster association are frailty models and marginal models. In this paper, we study the marginal proportional hazards model, where the structure of dependence between individuals within a cluster is unspecified. An estimation procedure is developed based on a pseudo-likelihood approach, and a risk set sampling method is proposed for the formulation of the pseudo-likelihood. The asymptotic properties of the proposed estimators are studied, and the related issues regarding the statistical efficiencies are discussed. The performances of the proposed estimator are demonstrated by the simulation studies. A data example from a child vitamin A supplementation trial in Nepal (Nepal Nutrition Intervention Project-Sarlahi, or NNIPS) is used to illustrate this methodology.     

Weighted Estimator for the Linear Transformation Models with Multivariate Failure Time Data

In this article, a simple and efficient weighted method is proposed to improve the estimation efficiency for the linear transformation models with multivariate failure time data. Asymptotic properties of the estimators with a closed-form variance-covariance matrix are established. In addition, a goodness-of-fit test is developed to evaluate the adequacy of the model. The performance of proposed method and the comparison on the efficiency between the proposed method and the working independence method (Lu, 2005) are conducted in finite-sample situation by simulation studies. Finally a real data set from the Busselton Population Health Surveys is illustrated to validate the proposed methodology. The related proofs of the theorems are given in the Appendix.     

Laws of the Iterated Logarithm and a Moderate Deviation of MLE for the Proportional Hazards Model with Incomplete Information

In this paper, we obtain a law of iterated logarithm, a Chung-type law of iterated logarithm, and a moderate deviation result of the maximum likelihood estimator (MLE) for the unknown regression parameter vector in a proportional hazards model with incomplete information.     

Proportional hazards estimate of the conditional survival function

We introduce a new estimator of the conditional survival function given some subset of the covariate values under a proportional hazards regression. The new estimate does not require estimating the base-line cumulative hazard function. An estimate of the variance is given and is easy to compute, involving only those quantities that are routinely calculated in a Cox model analysis. The asymptotic normality of the new estimate is shown by using a central limit theorem for Kaplan–Meier integrals. We indicate the straightforward extension of the estimation procedure under models with multiplicative relative risks, including non-proportional hazards, and to stratified and frailty models. The estimator is applied to a gastric cancer study where it is of interest to predict patients' survival based only on measurements obtained before surgery, the time at which the most important prognostic variable, stage, becomes known.