arXiv subjects

Yong Zang

Publications and source records attributed to Yong Zang.

5 recordsLinked to original sources

arXiv2026

BMW: Bayesian Model-Assisted Adaptive Phase II Clinical Trial Design for Win Ratio Statistic

The win ratio (WR) statistic is increasingly used to evaluate treatment effects based on prioritized composite endpoints, yet existing Bayesian adaptive designs are not directly applicable because the WR is a summary statistic derived from pairwise comparisons and does not correspond to a unique data-generating mechanism. We propose a Bayesian model-assisted adaptive design for randomized phase II clinical trials based on the WR statistic, referred to as the BMW design. The proposed design uses the joint asymptotic distribution of WR test statistics across interim and final analyses to compute posterior probabilities without specifying the underlying outcome distribution. The BMW design allows flexible interim monitoring with early stopping for futility or superiority and is extended to jointly evaluate efficacy and toxicity using a graphical testing procedure that controls the family-wise error rate (FWER). Simulation studies demonstrate that the BMW design maintains valid type I error and FWER control, achieves power comparable to conventional methods, and substantially reduces expected sample size. An R Shiny application is provided to facilitate practical implementation.

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arXiv2022

A Bayesian Precision Response-adaptive Phase II Clinical Trial Design for Radiotherapies with Competing Risk Survival Outcomes

Many phase II clinical trials have used survival outcomes as the primary endpoints in recent decades. Suppose the radiotherapy is evaluated in a phase II trial using survival outcomes. In that case, the competing risk issue often arises because the time to disease progression can be censored by the time to normal tissue complications, and vice versa. Besides, much literature has examined that patients receiving the same radiotherapy dose may yield distinct responses due to their heterogeneous radiation susceptibility statuses. Therefore, the "one-dose-fit-all" strategy often fails, and it is more relevant to evaluate the subgroup-specific treatment effect with the subgroup defined by the radiation susceptibility status. In this paper, we propose a Bayesian precision phase II trial design evaluating the subgroup-specific treatment effects of radiotherapy. We use the cause-specific hazard approach to model the competing risk survival outcomes. We propose restricting the candidate radiation doses based on each patient's radiation susceptibility status. Only the clinically feasible personalized dose will be considered, which enhances the benefit for the patients in the trial. In addition, we propose a stratified Bayesian adaptive randomization scheme such that more patients will be randomized to the dose reporting more favorable survival outcomes. Numerical studies have shown that the proposed design performed well and outperformed the conventional design ignoring the competing risk issue.

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arXiv2021

Spatially and Robustly Hybrid Mixture Regression Model for Inference of Spatial Dependence

In this paper, we propose a Spatial Robust Mixture Regression model to investigate the relationship between a response variable and a set of explanatory variables over the spatial domain, assuming that the relationships may exhibit complex spatially dynamic patterns that cannot be captured by constant regression coefficients. Our method integrates the robust finite mixture Gaussian regression model with spatial constraints, to simultaneously handle the spatial nonstationarity, local homogeneity, and outlier contaminations. Compared with existing spatial regression models, our proposed model assumes the existence a few distinct regression models that are estimated based on observations that exhibit similar response-predictor relationships. As such, the proposed model not only accounts for nonstationarity in the spatial trend, but also clusters observations into a few distinct and homogenous groups. This provides an advantage on interpretation with a few stationary sub-processes identified that capture the predominant relationships between response and predictor variables. Moreover, the proposed method incorporates robust procedures to handle contaminations from both regression outliers and spatial outliers. By doing so, we robustly segment the spatial domain into distinct local regions with similar regression coefficients, and sporadic locations that are purely outliers. Rigorous statistical hypothesis testing procedure has been designed to test the significance of such segmentation. Experimental results on many synthetic and real-world datasets demonstrate the robustness, accuracy, and effectiveness of our proposed method, compared with other robust finite mixture regression, spatial regression and spatial segmentation methods.

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arXiv2021

Component-wise Adaptive Trimming For Robust Mixture Regression

Parameter estimation of mixture regression model using the expectation maximization (EM) algorithm is highly sensitive to outliers. Here we propose a fast and efficient robust mixture regression algorithm, called Component-wise Adaptive Trimming (CAT) method. We consider simultaneous outlier detection and robust parameter estimation to minimize the effect of outlier contamination. Robust mixture regression has many important applications including in human cancer genomics data, where the population often displays strong heterogeneity added by unwanted technological perturbations. Existing robust mixture regression methods suffer from outliers as they either conduct parameter estimation in the presence of outliers, or rely on prior knowledge of the level of outlier contamination. CAT was implemented in the framework of classification expectation maximization, under which a natural definition of outliers could be derived. It implements a least trimmed squares (LTS) approach within each exclusive mixing component, where the robustness issue could be transformed from the mixture case to simple linear regression case. The high breakdown point of the LTS approach allows us to avoid the pre-specification of trimming parameter. Compared with multiple existing algorithms, CAT is the most competitive one that can handle and adaptively trim off outliers as well as heavy tailed noise, in different scenarios of simulated data and real genomic data. CAT has been implemented in an R package `RobMixReg' available in CRAN.

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arXiv2020

Supervised clustering of high dimensional data using regularized mixture modeling

Identifying relationships between molecular variations and their clinical presentations has been challenged by the heterogeneous causes of a disease. It is imperative to unveil the relationship between the high dimensional molecular manifestations and the clinical presentations, while taking into account the possible heterogeneity of the study subjects. We proposed a novel supervised clustering algorithm using penalized mixture regression model, called CSMR, to deal with the challenges in studying the heterogeneous relationships between high dimensional molecular features to a phenotype. The algorithm was adapted from the classification expectation maximization algorithm, which offers a novel supervised solution to the clustering problem, with substantial improvement on both the computational efficiency and biological interpretability. Experimental evaluation on simulated benchmark datasets demonstrated that the CSMR can accurately identify the subspaces on which subset of features are explanatory to the response variables, and it outperformed the baseline methods. Application of CSMR on a drug sensitivity dataset again demonstrated the superior performance of CSMR over the others, where CSMR is powerful in recapitulating the distinct subgroups hidden in the pool of cell lines with regards to their coping mechanisms to different drugs. CSMR represents a big data analysis tool with the potential to resolve the complexity of translating the clinical manifestations of the disease to the real causes underpinning it. We believe that it will bring new understanding to the molecular basis of a disease, and could be of special relevance in the growing field of personalized medicine.

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