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.     

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.     

Combined multiple testing of multivariate survival times by censored empirical likelihood

In each study testing the survival experience of one or more populations, one must not only choose an appropriate class of tests, but further an appropriate weight function. As the optimal choice depends on the true shape of the hazard ratio, one is often not capable of getting the best results with respect to a specific dataset. For the univariate case several methods were proposed to conquer this problem. However, most of the interesting datasets contain multivariate observations nowadays. In this work we propose a multivariate version of a method based on multiple constrained censored empirical likelihood where the constraints are formulated as linear functionals of the cumulative hazard functions. By considering the conditional hazards, we take the correlation between the components into account with the goal of obtaining a test that exhibits a high power irrespective of the shape of the hazard ratio under the alternative hypothesis.     

Regression analysis of case-cohort studies in the presence of dependent interval censoring

The case-cohort design is widely used as a means of reducing the cost in large cohort studies, especially when the disease rate is low and covariate measurements may be expensive, and has been discussed by many authors. In this paper, we discuss regression analysis of case-cohort studies that produce interval-censored failure time with dependent censoring, a situation for which there does not seem to exist an established approach. For inference, a sieve inverse probability weighting estimation procedure is developed with the use of Bernstein polynomials to approximate the unknown baseline cumulative hazard functions. The proposed estimators are shown to be consistent and the asymptotic normality of the resulting regression parameter estimators is established. A simulation study is conducted to assess the finite sample properties of the proposed approach and indicates that it works well in practical situations. The proposed method is applied to an HIV/AIDS case-cohort study that motivated this investigation.     

Assessing Major Accident Risks to Support Land‐Use Planning Using a Severity‐Vulnerability Combination Method: A Case Study in Dagushan Peninsula,China

Major accident risks posed by chemical hazards have raised major social concerns in today's China. Land‐use planning has been adopted by many countries as one of the essential elements for accident prevention. This article aims at proposing a method to assess major accident risks to support land‐use planning in the vicinity of chemical installations. This method is based on the definition of risk by the Accidental Risk Assessment Methodology for IndustrieS (ARAMIS) project and it is an expansion application of severity and vulnerability assessment tools. The severity and vulnerability indexes from the ARAMIS methodology are employed to assess both the severity and vulnerability levels, respectively. A risk matrix is devised to support risk ranking and compatibility checking. The method consists of four main steps and is presented in geographical information‐system‐based maps. As an illustration, the proposed method is applied in Dagushan Peninsula, China. The case study indicated that the method could not only aid risk regulations on existing land‐use planning, but also support future land‐use planning by offering alternatives or influencing the plans at the development stage, and thus further enhance the roles and influence of land‐use planning in the accident prevention activities in China.     

Semiparametric Efficient Estimation in the Generalized Odds-Rate Class of Regression Models for Right-Censored Time-to-Event Data

The generalized odds-rate class of regression models for time to event data is indexed by a non-negative constant and assumes thatg(S(t|Z)) = (t) + Zwhere g(s) = log(^-1(s-) for > 0, g₀(s) = log(- log s), S(t|Z) is the survival function of the time to event for an individual with qx1 covariate vector Z, is a qx1 vector of unknown regression parameters, and (t) is some arbitrary increasing function of t. When =0, this model is equivalent to the proportional hazards model and when =1, this model reduces to the proportional odds model. In the presence of right censoring, we construct estimators for and exp((t)) and show that they are consistent and asymptotically normal. In addition, we show that the estimator for is semiparametric efficient in the sense that it attains the semiparametric variance bound.