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.     

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.     

Anticipated Ethics and Regulatory Challenges in PCORnet: The National Patient-Centered Clinical Research Network

PCORnet, the National Patient-Centered Clinical Research Network, seeks to establish a robust national health data network for patient-centered comparative effectiveness research. This article reports the results of a PCORnet survey designed to identify the ethics and regulatory challenges anticipated in network implementation. A 12-item online survey was developed by leadership of the PCORnet Ethics and Regulatory Task Force; responses were collected from the 29 PCORnet networks. The most pressing ethics issues identified related to informed consent, patient engagement, privacy and confidentiality, and data sharing. High priority regulatory issues included IRB coordination, privacy and confidentiality, informed consent, and data sharing. Over 150 IRBs and five different approaches to managing multisite IRB review were identified within PCORnet. Further empirical and scholarly work, as well as practical and policy guidance, is essential if important initiatives that rely on comparative effectiveness research are to move forward.     

The generalized odd half-Cauchy family of distributions: Properties and applications

We introduce and study general mathematical properties of a new generator of continuous distributions with one extra parameter called the generalized odd half-Cauchy family. We present some special models and investigate the asymptotics and shapes. The new density function can be expressed as a linear mixture of exponentiated densities based on the same baseline distribution. We derive a power series for the quantile function. We discuss the estimation of the model parameters by maximum likelihood and prove empirically the flexibility of the new family by means of two real data sets.     

A comparative study of confidence intervals for negative binomial proportion

In this paper, we investigate four existing and three new confidence interval estimators for the negative binomial proportion (i.e., proportion under inverse/negative binomial sampling). An extensive and systematic comparative study among these confidence interval estimators through Monte Carlo simulations is presented. The performance of these confidence intervals are evaluated in terms of their coverage probabilities and expected interval widths. Our simulation studies suggest that the confidence interval estimator based on saddlepoint approximation is more appealing for large coverage levels (e.g., nominal level≤1% ) whereas the score confidence interval estimator is more desirable for those commonly used coverage levels (e.g., nominal level>1% ). We illustrate these confidence interval construction methods with a real data set from a maternal congenital heart disease study.     

Generalised K-S confidence regions: some exact results

One-sided confidence regions for continuous cumulative distribution function are constructed using empirical cumulative distribution functions and the generalized Kolmogorov-Smirnov distance. The band width of such regions becomes narrower in the right or left tail of the distribution. Significance levels necessary for implementation are given. Some other K-S type distances useful in constructing a confidence region with nonconstant width are also included.     

Affiliation networks with an increasing degree sequence

Affiliation network is one kind of two-mode social network with two different sets of nodes (namely, a set of actors and a set of social events) and edges representing the affiliation of the actors with the social events. Although a number of statistical models are proposed to analyze affiliation networks, the asymptotic behaviors of the estimator are still unknown or have not been properly explored. In this article, we study an affiliation model with the degree sequence as the exclusively natural sufficient statistic in the exponential family distributions. We establish the uniform consistency and asymptotic normality of the maximum likelihood estimator when the numbers of actors and events both go to infinity. Simulation studies and a real data example demonstrate our theoretical results.     

Semi-empirical likelihood inference for the ROC curve with missing data

The receiver operating characteristic (ROC) curve is one of the most commonly used methods to compare the diagnostic performance of two or more laboratory or diagnostic tests. In this paper, we propose semi-empirical likelihood based confidence intervals for ROC curves of two populations, where one population is parametric and the other one is non-parametric and both have missing data. After imputing missing values, we derive the semi-empirical likelihood ratio statistic and the corresponding likelihood equations. It is shown that the log-semi-empirical likelihood ratio statistic is asymptotically scaled chi-squared. The estimating equations are solved simultaneously to obtain the estimated lower and upper bounds of semi-empirical likelihood confidence intervals. We conduct extensive simulation studies to evaluate the finite sample performance of the proposed empirical likelihood confidence intervals with various sample sizes and different missing probabilities.