Tests of association between survival time and a continuous covariate

Proportional hazards model(Cox, 1972) is reviewed for the case of grouped data with one continuously measured covariate. This leads to a logit-rank procedure for tied data which is reduced to the test proposed by O’Brien(1978) and studied by O’Quigley and Prentice(1991) in the absence of ties. The proposed test is then applied to a special ranking method in order to study non-monotonic associations.     

LIKELIHOOD APPROXIMATIONS AND DISCRETE MODELS FOR TIED SURVIVAL DATA

ABSTRACT

Ties among event times are often recorded in survival studies. For example, in a two week laboratory study where event times are measured in days, ties are very likely to occur. The proportional hazards model might be used in this setting using an approximated partial likelihood function. This approximation works well when the number of ties is small. On the other hand, discrete regression models are suggested when the data are heavily tied. However, in many situations it is not clear which approach should be used in practice. In this work, empirical guidelines based on Monte Carlo simulations are provided. These recommendations are based on a measure of the amount of tied data present and the mean square error. An example illustrates the proposed criterion.     

A Frailty Model in Crossover Studies with Time-to-Event Response Variable

In this article, we develop a model to study treatment, period, carryover, and other applicable effects in a crossover design with a time-to-event response variable. Because time-to-event outcomes on different treatment regimens within the crossover design are correlated for an individual, we adopt a proportional hazards frailty model. If the frailty is assumed to have a gamma distribution, and the hazard rates are piecewise constant, then the likelihood function can be determined via closed-form expressions. We illustrate the methodology via an application to a data set from an asthma clinical trial and run simulations that investigate sensitivity of the model to data generated from different distributions.     

Estimation of Main Effect When Covariates Have Non-Proportional Hazards

The Cox proportional hazards (PH) regression model has been widely used to analyze survival data in clinical trials and observational studies. In addition to estimating the main treatment or exposure group effect, it is common to adjust for additional covariates using the Cox model. It is well known that violation of the PH assumption can lead to estimates that are biased and difficult to interpret, and model checking has become a routine procedure. However, such checking might focus on the primary group comparisons, and the assumption can still be violated when adjusting for many of the potential covariates. We study the effect of violation of the PH assumption of the covariates on the estimation of the main group effect in the Cox model. The results are summarized in terms of the bias and the coverage properties of the confidence intervals. Overall in randomized clinical trials, the bias caused by misspecifying the PH assumption on the covariates is no more than 15% in absolute value regardless of sample size. In observational studies where the covariates are likely correlated with the group variable, however, the bias can be very severe. The coverage properties largely depend on sample size, as expected, as bias becomes dominating with increasing sample size. These findings should serve as cautionary notes when adjusting for potential confounders in observational studies, as the violation of PH assumption on the confounders can lead to erroneous results.     

Small sample study on estimators of life distributions and of mean survival times using randomly censored data

Whereas large-sample properties of the estimators of survival distributions using censored data have been studied by many authors, exact results for small samples have been difficult to obtain. In this paper we obtain the exact expression for the ath moment (a > 0) of the Bayes estimator of survival distribution using the censored data under proportional hazard model. Using the exact expression we compute the exact mean, variance and MSE of the Bayes estimator. Also two estimators ofthe mean survival time based on the Kaplan-Meier estimator and the Bayes estimator are compared for small samples under proportional hazards.     

ASYMPTOTIC AND SMALL SAMPLE STATISTICAL PROPERTIES OF RANDOM FRAILTY VARIANCE ESTIMATES FOR SHARED GAMMA FRAILTY MODELS

This paper concerns maximum likelihood estimation for the semiparametric shared gamma frailty model; that is the Cox proportional hazards model with the hazard function multiplied by a gamma random variable with mean 1 and variance θ. A hybrid ML-EM algorithm is applied to 26 400 simulated samples of 400 to 8000 observations with Weibull hazards. The hybrid algorithm is much faster than the standard EM algorithm, faster than standard direct maximum likelihood (ML, Newton Raphson) for large samples, and gives almost identical results to the penalised likelihood method in S-PLUS 2000. When the true value θ₀ of θ is zero, the estimates of θ are asymptotically distributed as a 50–50 mixture between a point mass at zero and a normal random variable on the positive axis. When θ₀ > 0, the asymptotic distribution is normal. However, for small samples, simulations suggest that the estimates of θ are approximately distributed as an x ? (100 ? x)% mixture, 0 ≤ x ≤ 50, between a point mass at zero and a normal random variable on the positive axis even for θ₀ > 0. In light of this, p-values and confidence intervals need to be adjusted accordingly. We indicate an approximate method for carrying out the adjustment.     

Analyzing Cohort Mortality Data

Several methods for analyzing data from mortality studies of occupationally or environmentally exposed cohorts are shown to be special cases of a single procedure. The procedure assumes a proportional hazards model for exposure effects and represents the log-likelihood kernel for the data as that of N independent Poisson variates, where N is the total number of person-units of mortality observation time in the study. It formalizes and justifies the epidemiological techniques of classifying deaths and person-months of study time into categories defined by exposure and other covariates, and of computing standardized mortality ratios and indirectly standardized death rates. Parameters representing exposure effects can be estimated by using standard software packages. Special cases and applications are described in the context of lung cancer mortality among U.S. uranium miners.     

Estimation of the additive hazards model with interval-censored data and missing covariates

The additive hazards model is one of the most commonly used regression models in the analysis of failure time data and many methods have been developed for its inference in various situations. However, no established estimation procedure exists when there are covariates with missing values and the observed responses are interval-censored; both types of complications arise in various settings including demographic, epidemiological, financial, medical and sociological studies. To address this deficiency, we propose several inverse probability weight-based and reweighting-based estimation procedures for the situation where covariate values are missing at random. The resulting estimators of regression model parameters are shown to be consistent and asymptotically normal. The numerical results that we report from a simulation study suggest that the proposed methods work well in practical situations. An application to a childhood cancer survival study is provided. The Canadian Journal of Statistics 48: 499–517; 2020 © 2020 Statistical Society of Canada     

An Optimization‐Based Framework for the Identification of Vulnerabilities in Electric Power Grids Exposed to Natural Hazards

This article proposes a novel mathematical optimization framework for the identification of the vulnerabilities of electric power infrastructure systems (which is a paramount example of critical infrastructure) due to natural hazards. In this framework, the potential impacts of a specific natural hazard on an infrastructure are first evaluated in terms of failure and recovery probabilities of system components. Then, these are fed into a bi‐level attacker–defender interdiction model to determine the critical components whose failures lead to the largest system functionality loss. The proposed framework bridges the gap between the difficulties of accurately predicting the hazard information in classical probability‐based analyses and the over conservatism of the pure attacker–defender interdiction models. Mathematically, the proposed model configures a bi‐level max‐min mixed integer linear programming (MILP) that is challenging to solve. For its solution, the problem is casted into an equivalent one‐level MILP that can be solved by efficient global solvers. The approach is applied to a case study concerning the vulnerability identification of the georeferenced RTS24 test system under simulated wind storms. The numerical results demonstrate the effectiveness of the proposed framework for identifying critical locations under multiple hazard events and, thus, for providing a useful tool to help decisionmakers in making more‐informed prehazard preparation decisions.     

Risk Perception: Reflections on 40 Years of Research

Numerous studies and practical experiences with risk have demonstrated the importance of risk perceptions for people's behavior. In this narrative review, we describe and reflect upon some of the lines of research that we feel have been important in helping us understand the factors and processes that shape people's risk perceptions. In our review, we propose that much of the research on risk perceptions to date can be grouped according to three dominant perspectives and, thus, approaches to study design; they are: the characteristics of hazards, the characteristics of risk perceivers, and the application of heuristics to inform risk judgments. In making these distinctions, we also highlight what we see as outstanding challenges for researchers and practitioners. We also highlight a few new research questions that we feel warrant attention.