An improved two-stage procedure to compare hazard curves

Qiu and Sheng has proposed a powerful and robust two-stage procedure to compare two hazard rate functions. In this paper we improve their method by using the Fisher test to combine the asymptotically independent p-values obtained from the two stages of their procedure. In addition, we extend the procedure to situations with multiple hazard rate functions. Our comprehensive simulation study shows that the proposed method has a good performance in terms of controlling the type I error rate and of detecting power. Three real data applications are considered for illustrating the use of the new method.     

Generalizing the standardized hazard ratio to multivariate proportional hazards regression,with an application to clinical~genomic studies

The standardized hazard ratio for univariate proportional hazards regression is generalized as a scalar to multivariate proportional hazards regression. Estimators of the standardized log hazard ratio are developed, with corrections for bias and for regression to the mean in high-dimensional analyses. Tests of point and interval null hypotheses and confidence intervals are constructed. Cohort sampling study designs, commonly used in prospective–retrospective clinical genomic studies, are accommodated.     

Using In Vitro High‐Throughput Screening Data for Predicting Benzo[k]Fluoranthene Human Health Hazards

Today there are more than 80,000 chemicals in commerce and the environment. The potential human health risks are unknown for the vast majority of these chemicals as they lack human health risk assessments, toxicity reference values, and risk screening values. We aim to use computational toxicology and quantitative high‐throughput screening (qHTS) technologies to fill these data gaps, and begin to prioritize these chemicals for additional assessment. In this pilot, we demonstrate how we were able to identify that benzo[k]fluoranthene may induce DNA damage and steatosis using qHTS data and two separate adverse outcome pathways (AOPs). We also demonstrate how bootstrap natural spline‐based meta‐regression can be used to integrate data across multiple assay replicates to generate a concentration–response curve. We used this analysis to calculate an in vitro point of departure of 0.751 μM and risk‐specific in vitro concentrations of 0.29 μM and 0.28 μM for 1:1,000 and 1:10,000 risk, respectively, for DNA damage. Based on the available evidence, and considering that only a single HSD17B4 assay is available, we have low overall confidence in the steatosis hazard identification. This case study suggests that coupling qHTS assays with AOPs and ontologies will facilitate hazard identification. Combining this with quantitative evidence integration methods, such as bootstrap meta‐regression, may allow risk assessors to identify points of departure and risk‐specific internal/in vitro concentrations. These results are sufficient to prioritize the chemicals; however, in the longer term we will need to estimate external doses for risk screening purposes, such as through margin of exposure methods.     

Is prenatal sex selection associated with lower female child mortality?

I examine whether prenatal sex selection has substituted postnatal excess female mortality by analysing the dynamics of child sex ratios between 1980 and 2015 using country-level life table data. I decompose changes in child sex ratios into a ‘fertility’ component attributable to prenatal sex selection and a ‘mortality’ component attributable to sex differentials in postnatal survival. Although reductions in numbers of excess female deaths have accompanied increases in missing female births in all countries experiencing the emergence of prenatal sex selection, relative excess female mortality has persisted in some countries but not others. In South Korea, Armenia, and Azerbaijan, mortality reductions favouring girls accompanied increases in prenatal sex selection. In India, excess female mortality was much higher and largely stable as prenatal sex selection emerged, but slight reductions were seen in the 2000s. In China, although absolute measures showed reductions, relative excess female mortality persisted as prenatal sex selection increased.     

Early stopping in seamless phase I/II clinical trials

In recent years, seamless phase I/II clinical trials have drawn much attention, as they consider both toxicity and efficacy endpoints in finding an optimal dose (OD). Engaging an appropriate number of patients in a trial is a challenging task. This paper attempts a dynamic stopping rule to save resources in phase I/II trials. That is, the stopping rule aims to save patients from unnecessary toxic or subtherapeutic doses. We allow a trial to stop early when widths of the confidence intervals for the dose-response parameters become narrower or when the sample size is equal to a predefined size, whichever comes first. The simulation study of dose-response scenarios in various settings demonstrates that the proposed stopping rule can engage an appropriate number of patients. Therefore, we suggest its use in clinical trials.     

Elasticity function of a discrete random variable and its properties

Elasticity (or elasticity function) is a new concept that allows us to characterize the probability distribution of any random variable in the same way as characteristic functions and hazard and reverse hazard functions do. Initially defined for continuous variables, it was necessary to extend the definition of elasticity and study its properties in the case of discrete variables. A first attempt to define discrete elasticity is seen in Veres-Ferrer and Pavía (2014a). This paper develops this definition and makes a comparative study of its properties, relating them to the properties shown by discrete hazard and reverse hazard, as both defined in Chechile (2011). Similar to continuous elasticity, one of the most interesting properties of discrete elasticity focuses on the rate of change that this undergoes throughout its support. This paper centers on the study of the rate of change and develops a set of properties that allows us to carry out a detailed analysis. Finally, it addresses the calculation of the elasticity for the resulting variable obtained from discretizing a continuous random variable, distinguishing whether its domain is in real positives or negatives.     

Hypothesis Testing in a Rayleigh Diffusion Model

Applying the large and moderate deviations for the log-likelihood ratio of the Rayleigh diffusion model, we give the negative regions in testing Rayleigh diffusion model and obtain the decay rates of the error probabilities.     

Tail Behavior and Limit Distribution of Maximum of Logarithmic General Error Distribution

Logarithmic general error distribution, an extension of the log-normal distribution, is proposed. Some interesting properties of the log GED are derived. These properties are applied to establish the asymptotic behavior of the ratio of probability densities and the ratio of the tails of the logarithmic general error and log-normal distributions, and to derive the asymptotic distribution of the partial maximum of an independent and identically distributed sequence obeying the log GED.     

Optimal design of repetitive group sampling plans for Weibull and gamma distributions with applications and comparison to the Birnbaum–Saunders distribution

In this paper, we propose a multiple deferred state repetitive group sampling plan which is a new sampling plan developed by incorporating the features of both multiple deferred state sampling plan and repetitive group sampling plan, for assuring Weibull or gamma distributed mean life of the products. The quality of the product is represented by the ratio of true mean life and specified mean life of the products. Two points on the operating characteristic curve approach is used to determine the optimal parameters of the proposed plan. The plan parameters are determined by formulating an optimization problem for various combinations of producer's risk and consumer's risk for both distributions. The sensitivity analysis of the proposed plan is discussed. The implementation of the proposed plan is explained using real-life data and simulated data. The proposed plan under Weibull distribution is compared with the existing sampling plans. The average sample number (ASN) of the proposed plan and failure probability of the product are obtained under Weibull, gamma and Birnbaum–Saunders distributions for a specified value of shape parameter and compared with each other. In addition, a comparative study is made between the ASN of the proposed plan under Weibull and gamma distributions.