Development of predictive signatures for treatment selection in precision medicine with survival outcomes

For survival endpoints in subgroup selection, a score conversion model is often used to convert the set of biomarkers for each patient into a univariate score and using the median of the univariate scores to divide the patients into biomarker‐positive and biomarker‐negative subgroups. However, this may lead to bias in patient subgroup identification regarding the 2 issues: (1) treatment is equally effective for all patients and/or there is no subgroup difference; (2) the median value of the univariate scores as a cutoff may be inappropriate if the sizes of the 2 subgroups are differ substantially. We utilize a univariate composite score method to convert the set of patient's candidate biomarkers to a univariate response score. We propose applying the likelihood ratio test (LRT) to assess homogeneity of the sampled patients to address the first issue. In the context of identification of the subgroup of responders in adaptive design to demonstrate improvement of treatment efficacy (adaptive power), we suggest that subgroup selection is carried out if the LRT is significant. For the second issue, we utilize a likelihood‐based change‐point algorithm to find an optimal cutoff. Our simulation study shows that type I error generally is controlled, while the overall adaptive power to detect treatment effects sacrifices approximately 4.5% for the simulation designs considered by performing the LRT; furthermore, the change‐point algorithm outperforms the median cutoff considerably when the subgroup sizes differ substantially.     

Bayesian estimation of reliability using time-to-failure distribution of parametric degradation models

This paper focusses on computing the Bayesian reliability of components whose performance characteristics (degradation – fatigue and cracks) are observed during a specified period of time. Depending upon the nature of degradation data collected, we fit a monotone increasing or decreasing function for the data. Since the components are supposed to have different lifetimes, the rate of degradation is assumed to be a random variable. At a critical level of degradation, the time to failure distribution is obtained. The exponential and power degradation models are studied and exponential density function is assumed for the random variable representing the rate of degradation. The maximum likelihood estimator and Bayesian estimator of the parameter of exponential density function, predictive distribution, hierarchical Bayes approach and robustness of the posterior mean are presented. The Gibbs sampling algorithm is used to obtain the Bayesian estimates of the parameter. Illustrations are provided for the train wheel degradation data.     

Mixtures of regression models with incomplete and noisy data

The estimation of the mixtures of regression models is usually based on the normal assumption of components and maximum likelihood estimation of the normal components is sensitive to noise, outliers, or high-leverage points. Missing values are inevitable in many situations and parameter estimates could be biased if the missing values are not handled properly. In this article, we propose the mixtures of regression models for contaminated incomplete heterogeneous data. The proposed models provide robust estimates of regression coefficients varying across latent subgroups even under the presence of missing values. The methodology is illustrated through simulation studies and a real data analysis.     

Likelihood ratio order of parallel systems under multiple-outlier models

This paper studies the likelihood ratio ordering of parallel systems under multiple-outlier models. We introduce a partial order, the so-called θ-order, and show that the θ-order between the parameter vectors of the parallel systems implies the likelihood ratio order between the systems.     

Fixed T dynamic panel data estimators with multifactor errors

This article analyzes a growing group of fixed T dynamic panel data estimators with a multifactor error structure. We use a unified notational approach to describe these estimators and discuss their properties in terms of deviations from an underlying set of basic assumptions. Furthermore, we consider the extendability of these estimators to practical situations that may frequently arise, such as their ability to accommodate unbalanced panels and common observed factors. Using a large-scale simulation exercise, we consider scenarios that remain largely unexplored in the literature, albeit being of great empirical relevance. In particular, we examine (i) the effect of the presence of weakly exogenous covariates, (ii) the effect of changing the magnitude of the correlation between the factor loadings of the dependent variable and those of the covariates, (iii) the impact of the number of moment conditions on bias and size for GMM estimators, and finally (iv) the effect of sample size. We apply each of these estimators to a crime application using a panel data set of local government authorities in New South Wales, Australia; we find that the results bear substantially different policy implications relative to those potentially derived from standard dynamic panel GMM estimators. Thus, our study may serve as a useful guide to practitioners who wish to allow for multiplicative sources of unobserved heterogeneity in their model.     

Sample size re‐estimation incorporating prior information on a nuisance parameter

Prior information is often incorporated informally when planning a clinical trial. Here, we present an approach on how to incorporate prior information, such as data from historical clinical trials, into the nuisance parameter–based sample size re‐estimation in a design with an internal pilot study. We focus on trials with continuous endpoints in which the outcome variance is the nuisance parameter. For planning and analyzing the trial, frequentist methods are considered. Moreover, the external information on the variance is summarized by the Bayesian meta‐analytic‐predictive approach. To incorporate external information into the sample size re‐estimation, we propose to update the meta‐analytic‐predictive prior based on the results of the internal pilot study and to re‐estimate the sample size using an estimator from the posterior. By means of a simulation study, we compare the operating characteristics such as power and sample size distribution of the proposed procedure with the traditional sample size re‐estimation approach that uses the pooled variance estimator. The simulation study shows that, if no prior‐data conflict is present, incorporating external information into the sample size re‐estimation improves the operating characteristics compared to the traditional approach. In the case of a prior‐data conflict, that is, when the variance of the ongoing clinical trial is unequal to the prior location, the performance of the traditional sample size re‐estimation procedure is in general superior, even when the prior information is robustified. When considering to include prior information in sample size re‐estimation, the potential gains should be balanced against the risks.     

Self-exciting threshold models for time series of counts with a finite range

In this article, an integer-valued self-exciting threshold model with a finite range based on the binomial INARCH(1) model is proposed. Important stochastic properties are derived, and approaches for parameter estimation are discussed. A real-data example about the regional spread of public drunkenness in Pittsburgh demonstrates the applicability of the new model in comparison to existing models. Feasible modifications of the model are presented, which are designed to handle special features such as zero-inflation.     

New innovational outlier unit root test with a break at an unknown time

The Perron test which is based on a Dickey–Fuller test regression is a commonly employed approach to test for a unit root in the presence of a structural break of unknown timing. In the case of an innovational outlier (IO), the Perron test tends to exhibit spurious rejections in finite samples when the break occurs under the null hypothesis. In the present paper, a new Perron-type IO unit root test is developed. It is shown in Monte Carlo experiments that the new test does not over-reject the null hypothesis. Even for the case of a level and slope break for trending data, the empirical size is near its nominal level. The test distribution equals the case of a known break date. Furthermore, the test is able to identify the true break date very accurately even for small breaks. As an application serves the Nelson–Plosser data set.     

Another look at the robustness of colton's model for comparing two medical treatments

The robustness of an extended version of Colton's decision theoretic model is considered. The extended version includes the losses due to the patients who are not entered in the experiment, but require treatment while the experiment is in progress. Among the topics considered are the effects of risk of using a sample size considerably less than the optimum, use of an incorrect patient horizon, application of a modified loss function, and use of a two point prior distribution. It is shown that the investigated model is robust with respect to all these changes with the exception of the use of the modified prior density.