Group sequential monitoring based on the weighted log‐rank test statistic with the Fleming–Harrington class of weights in cancer vaccine studies

In recent years, immunological science has evolved, and cancer vaccines are now approved and available for treating existing cancers. Because cancer vaccines require time to elicit an immune response, a delayed treatment effect is expected and is actually observed in drug approval studies. Accordingly, we propose the evaluation of survival endpoints by weighted log‐rank tests with the Fleming–Harrington class of weights. We consider group sequential monitoring, which allows early efficacy stopping, and determine a semiparametric information fraction for the Fleming–Harrington family of weights, which is necessary for the error spending function. Moreover, we give a flexible survival model in cancer vaccine studies that considers not only the delayed treatment effect but also the long‐term survivors. In a Monte Carlo simulation study, we illustrate that when the primary analysis is a weighted log‐rank test emphasizing the late differences, the proposed information fraction can be a useful alternative to the surrogate information fraction, which is proportional to the number of events. Copyright © 2016 John Wiley & Sons, Ltd.     

A Proportional Hazards Regression Model for the Subdistribution with Covariates‐adjusted Censoring Weight for Competing Risks Data

With competing risks data, one often needs to assess the treatment and covariate effects on the cumulative incidence function. Fine and Gray proposed a proportional hazards regression model for the subdistribution of a competing risk with the assumption that the censoring distribution and the covariates are independent. Covariate‐dependent censoring sometimes occurs in medical studies. In this paper, we study the proportional hazards regression model for the subdistribution of a competing risk with proper adjustments for covariate‐dependent censoring. We consider a covariate‐adjusted weight function by fitting the Cox model for the censoring distribution and using the predictive probability for each individual. Our simulation study shows that the covariate‐adjusted weight estimator is basically unbiased when the censoring time depends on the covariates, and the covariate‐adjusted weight approach works well for the variance estimator as well. We illustrate our methods with bone marrow transplant data from the Center for International Blood and Marrow Transplant Research. Here, cancer relapse and death in complete remission are two competing risks.     

Combining Inverse Probability Weighting and Multiple Imputation to Improve Robustness of Estimation

Inverse probability weighting (IPW) and multiple imputation are two widely adopted approaches dealing with missing data. The former models the selection probability, and the latter models data distribution. Consistent estimation requires correct specification of corresponding models. Although the augmented IPW method provides an extra layer of protection on consistency, it is usually not sufficient in practice as the true data‐generating process is unknown. This paper proposes a method combining the two approaches in the same spirit of calibration in sampling survey literature. Multiple models for both the selection probability and data distribution can be simultaneously accounted for, and the resulting estimator is consistent if any model is correctly specified. The proposed method is within the framework of estimating equations and is general enough to cover regression analysis with missing outcomes and/or missing covariates. Results on both theoretical and numerical investigation are provided.     

Inference on a progressive type I interval-censored truncated normal distribution

In this paper, we consider the problem of making statistical inference for a truncated normal distribution under progressive type I interval censoring. We obtain maximum likelihood estimators of unknown parameters using the expectation-maximization algorithm and in sequel, we also compute corresponding midpoint estimates of parameters. Estimation based on the probability plot method is also considered. Asymptotic confidence intervals of unknown parameters are constructed based on the observed Fisher information matrix. We obtain Bayes estimators of parameters with respect to informative and non-informative prior distributions under squared error and linex loss functions. We compute these estimates using the importance sampling procedure. The highest posterior density intervals of unknown parameters are constructed as well. We present a Monte Carlo simulation study to compare the performance of proposed point and interval estimators. Analysis of a real data set is also performed for illustration purposes. Finally, inspection times and optimal censoring plans based on the expected Fisher information matrix are discussed.     

Outlier detection and robust variable selection via the penalized weighted LAD-LASSO method

This paper studies the outlier detection and robust variable selection problem in the linear regression model. The penalized weighted least absolute deviation (PWLAD) regression estimation method and the adaptive least absolute shrinkage and selection operator (LASSO) are combined to simultaneously achieve outlier detection, and robust variable selection. An iterative algorithm is proposed to solve the proposed optimization problem. Monte Carlo studies are evaluated the finite-sample performance of the proposed methods. The results indicate that the finite sample performance of the proposed methods performs better than that of the existing methods when there are leverage points or outliers in the response variable or explanatory variables. Finally, we apply the proposed methodology to analyze two real datasets.     

Semiparametric regression of clustered current status data

This paper discusses regression analysis of clustered current status data under semiparametric additive hazards models. In particular, we consider the situation when cluster sizes can be informative about correlated failure times from the same cluster. To address the problem, we present estimating equation-based estimation procedures and establish asymptotic properties of the resulting estimates. Finite sample performance of the proposed method is assessed through an extensive simulation study, which indicates the procedure works well. The method is applied to a motivating data set from a lung tumorigenicity study.     

Toward an integrated Bayesian network approach to measurement error detection and correction

In this article, the quality of data produced by national statistical institutes and by governmental institutions is considered. In particular, the problem of measurement error is analyzed and an integrated Bayesian network decision support system based on non-parametric Bayesian networks is proposed for its detection and correction. Non-parametric Bayesian networks are graphical models expressing dependence structure via bivariate copulas associated to the edges of the graph. The network structure and the misreport probability are estimated using a validation sample. The Bayesian network model is proposed to decide: (i) which records have to be corrected; (ii) the kind and amount of correction to be adopted. The proposed correction procedure is applied to the Banca d’Italia Survey on Household Income and Wealth and, specifically, the bond amounts are analyzed. Finally, the sensitivity of the conditional distribution of the true value random variable given the observed one to different evidence configurations is studied.     

An improved cluster two-stage randomized response model

In this paper, Abdelfatah and Mazloum's (2015) two-stage randomized response model is extended to unequal probability sampling and stratified unequal probability sampling, both with and without replacement. The extended models result in more efficient estimators than Lee et al.'s (2014) estimators of the proportion of the population having a sensitive attribute.     

MSE performance of the weighted average estimators consisting of shrinkage estimators when each individual regression coefficient is estimated

In this paper, we analytically derive the exact formula for the mean squared error (MSE) of two weighted average (WA) estimators for each individual regression coefficient. Further, we execute numerical evaluations to investigate small sample properties of the WA estimators, and compare the MSE performance of the WA estimators with the other shrinkage estimators and the usual OLS estimator. Our numerical results show that (1) the WA estimators have smaller MSE than the other shrinkage estimators and the OLS estimator over a wide region of parameter space; (2) the range where the relative MSE of the WA estimator is smaller than that of the OLS estimator gets narrower as the number of explanatory variables k increases.