arXiv subjects

Dehua Bi

Publications and source records attributed to Dehua Bi.

7 recordsLinked to original sources

arXiv2026

Interpreting Hierarchical Composite Endpoints with Survival and Longitudinal Outcomes: Application to Amyotrophic Lateral Sclerosis Trials

Hierarchical composite endpoints combining survival and longitudinal functional outcomes are increasingly used in clinical trials, especially when death precludes subsequent functional assessment. The Finkelstein--Schoenfeld strategy analyzes such endpoints through prioritized pairwise comparisons, with survival compared before function. In amyotrophic lateral sclerosis (ALS), this strategy is implemented in the Combined Assessment of Function and Survival (CAFS), which combines survival with the ALS Functional Rating Scale Revised. Although such endpoints provide a clinically meaningful summary of overall treatment benefit, investigators may also want to understand whether the treatment effect is driven by survival, functional outcome, or both. Motivated by the estimand framework, we use ALS-informed simulations from a joint longitudinal--survival model to study settings in which treatment effects on survival and function align or conflict. The simulations show that decomposing the composite win probability into survival and survivor-based functional contributions clarifies their relative roles and separates the composite treatment-benefit question from function-focused questions, including the while-alive comparison and conceptual alternatives based on hypothetical and always-survivor estimands. The functional win probability underlying the while-alive comparison can be subject to survivor-selection bias when treatment affects survival, and inverse-probability weighting can attenuate selection induced by measured predictors under appropriate assumptions. Brief supporting analyses based on principal stratification and multiply robust estimation illustrate the always-survivor estimand. This framework provides practical guidance for reporting and interpreting hierarchical composite endpoints, with CAFS in ALS serving as a concrete motivating example.

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arXiv2026

RECaST-Surv: A Calibrated Borrowing Method for Survival Endpoints in Unequal Randomized Trials

Randomized trials with limited concurrent control information---including but not limited to unequal-randomization settings---can offer ethical and practical advantages, especially in pediatric and rare diseases, but they often lose power because fewer control patients are available for direct comparison. Borrowing information from external controls may improve efficiency, but can also inflate the Type I error rate when the external and trial populations are not sufficiently comparable. We propose RECaST-Surv, a Bayesian transfer-learning framework for time-to-event outcomes that extends the RECaST method to survival settings. The method learns a structural survival model from external control data and calibrates it to the concurrent control arm of the current trial through a Cauchy random effect. To improve frequentist operating characteristics, we further develop a bootstrap-based procedure to calibrate the testing rule for Type I error control. RECaST-Surv can accommodate multiple external datasets and requires only summary-level information from external sources. Simulation studies show that the method maintains near-nominal Type I error across challenging settings while improving power by roughly 10%--12% over standard analyses. In an Amyotrophic Lateral Sclerosis trial emulation, RECaST-Surv increased power from 82.8% to 95.7% relative to the no-borrowing RCT analysis, while maintaining acceptable error control.

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arXiv2026

TWICEBEE: A Two-stage Intra-patient Curve-free Bayesian Decision-Theoretic Dose Escalation Design

We propose a novel Phase I intra-patient dose-escalation design tailored for multi-cycle immunotherapy settings, in which toxicity at a fixed dose level is clinically expected to decrease over successive treatment cycles. This design was motivated by a phase I trial of CAR T cell therapy, an emerging cellular immunotherapy with established applications in cancer and growing investigation in autoimmune disease. The design is intended for settings in which nonincreasing cycle-specific toxicity assumption is clinically justified. Specifically, we build on the extrapolation property of the modified curve-free Bayesian decision-theoretic (c-CFBD) design for two-agent trials (Xu, et al. 2025), treating treatment cycle as a second dimension. By redefining the partial order, the c-CFBD framework can accommodate the reduction in toxicity across cycles. The proposed design adopts a two-stage structure: an initial accelerated titration stage to rapidly explore dose levels, followed by a c-CFBD stage to improve safety and estimate the cycle-specific maximum tolerated dose sequence. Simulation studies across a range of scenarios demonstrate favorable operating characteristics.

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arXiv2026

BESS: A Bayesian Estimator of Sample Size

We consider a Bayesian framework for estimating the sample size of a clinical trial. The new approach, called BESS, is built upon three pillars: Sample size of the trial, Evidence from the observed data, and Confidence of the final decision in the posterior inference. It uses a simple logic of "given the evidence from data, a specific sample size can achieve a degree of confidence in trial success." The key distinction between BESS and standard sample size estimation (SSE) is that SSE, typically based on Frequentist inference, specifies the true parameters values in its calculation to achieve properties under repeated sampling while BESS assumes possible outcome from the observed data to achieve high posterior probabilities of trial success. As a result, the calibration of the sample size is directly based on the probability of making a correct decision rather than type I or type II error rates. We demonstrate that BESS leads to a more interpretable statement for investigators, and can easily accommodates prior information as well as sample size re-estimation. We explore its performance in comparison to the standard SSE and demonstrate its usage through a case study of oncology optimization trial. An R tool is available at https://ccte.uchicago.edu/BESS.

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arXiv2025

Balancing the effective sample size in prior across different doses in the curve-free Bayesian decision-theoretic design for dose-finding trials

The primary goal of dose allocation in phase I trials is to minimize patient exposure to subtherapeutic or excessively toxic doses, while accurately recommending a phase II dose that is as close as possible to the maximum tolerated dose (MTD). Fan et al. (2012) introduced a curve-free Bayesian decision-theoretic design (CFBD), which leverages the assumption of a monotonic dose-toxicity relationship without directly modeling dose-toxicity curves. This approach has also been extended to drug combinations for determining the MTD (Lee et al., 2017). Although CFBD has demonstrated improved trial efficiency by using fewer patients while maintaining high accuracy in identifying the MTD, it may artificially inflate the effective sample sizes for the updated prior distributions, particularly at the lowest and highest dose levels. This can lead to either overshooting or undershooting the target dose. In this paper, we propose a modification to CFBD's prior distribution updates that balances effective sample sizes across different doses. Simulation results show that with the modified prior specification, CFBD achieves a more focused dose allocation at the MTD and offers more precise dose recommendations with fewer patients on average. It also demonstrates robustness to other well-known dose finding designs in literature.

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arXiv2023

A Class of Dependent Random Distributions Based on Atom Skipping

We propose the Plaid Atoms Model (PAM), a novel Bayesian nonparametric model for grouped data. Founded on an idea of `atom skipping', PAM is part of a well-established category of models that generate dependent random distributions and clusters across multiple groups. Atom skipping referrs to stochastically assigning 0 weights to atoms in an infinite mixture. Deploying atom skipping across groups, PAM produces a dependent clustering pattern with overlapping and non-overlapping clusters across groups. As a result, interpretable posterior inference is possible such as reporting the posterior probability of a cluster being exclusive to a single group or shared among a subset of groups. We discuss the theoretical properties of the proposed and related models. Minor extensions of the proposed model for multivariate or count data are presented. Simulation studies and applications using real-world datasets illustrate the performance of the new models with comparison to existing models.

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arXiv2023

PAM-HC: A Bayesian Nonparametric Construction of Hybrid Control for Randomized Clinical Trials Using External Data

It is highly desirable to borrow information from external data to augment a control arm in a randomized clinical trial, especially in settings where the sample size for the control arm is limited. However, a main challenge in borrowing information from external data is to accommodate potential heterogeneous subpopulations across the external and trial data. We apply a Bayesian nonparametric model called Plaid Atoms Model (PAM) to identify overlapping and unique subpopulations across datasets, with which we restrict the information borrowing to the common subpopulations. This forms a hybrid control (HC) that leads to more precise estimation of treatment effects Simulation studies demonstrate the robustness of the new method, and an application to an Atopic Dermatitis dataset shows improved treatment effect estimation.

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