arXiv subjects

Chenqi Fu

Publications and source records attributed to Chenqi Fu.

3 recordsLinked to original sources

arXiv2026

Leveraging External Controls for Treatment Switching in Randomized Controlled Trials: A Weighted Causal Inference Framework for Overall Survival

In many oncology clinical trials where overall survival is a key endpoint, patients are permitted to switch from the control arm to the experimental treatment arm or other suitable therapies. Switching can occur for various reasons, including disease progression. This violates the causal guarantees of randomized treatment assignment, resulting in biased treatment effect estimates. Existing methods often require strong assumptions, complicated model specifications, or both. In this paper, we propose a general framework that incorporates external controls to account for treatment switching in randomized controlled trials. Leveraging the synthetic control method and balancing weights from observational causal inference, we propose several estimators that use multiple imputation and time-varying weights to adjust for treatment switching. We also discuss approaches to selecting the risk set of external controls to impute from. Through extensive simulation studies, we show that our proposed methods lead to meaningful statistical improvements relative to standard adjustment methods that utilize external controls in naive ways or those that do not utilize external controls at all. We then demonstrate the utility of our external control-based approaches with two phase III oncology trials.

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arXiv2025

WOW: WAIC-Optimized Gating of Mixture Priors for External Data Borrowing

The integration of external data using Bayesian mixture priors has become a powerful approach in clinical trials, offering significant potential to improve trial efficiency. Despite their strengths in analytical tractability and practical flexibility, existing methods such as the robust meta-analytic-predictive (rMAP) and self-adapting mixture (SAM) often presume borrowing without rigorously assessing whether external information is appropriate to incorporate. When external and concurrent data are discordant, excessive borrowing can bias estimation and lead to misleading conclusions. To address this, we introduce WOW, a Kullback-Leibler-based gating strategy guided by the widely applicable information criterion (WAIC). Within the mixture-prior framework, WAIC-Optimized Weighting (WOW) conducts a preliminary compatibility assessment between external and concurrent trial data to determine eligibility for borrowing. Only if this gating criterion is satisfied does borrowing proceed; a downstream mixture prior procedure, using user-specified fixed or adaptive weights, can then be applied to determine the amount of borrowing. Simulation studies demonstrate that incorporating the WOW strategy before Bayesian mixture prior borrowing methods effectively mitigates excessive borrowing and improves estimation accuracy. A real-data illustration further highlights the feasibility and interpretability of the proposed gate-then-borrow strategy. By providing a practical safeguard against inappropriate borrowing, WOW strengthens the reliability of mixture-prior methods and supports better decision-making in clinical trials.

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arXiv2022

Evidence synthesis with reconstructed survival data

We present a general approach to synthesizing evidence of time-to-event endpoints in meta-analyses of aggregate data (AD). Our work goes beyond most previous meta-analytic research by using reconstructed survival data as a source of information. A Bayesian multilevel regression model, called the "meta-analysis of reconstructed survival data" (MARS), is introduced, by modeling and integrating reconstructed survival information with other types of summary data, to estimate the hazard ratio function and survival probabilities. The method attempts to reduce selection bias, and relaxes the presumption of proportional hazards in individual clinical studies from the conventional approaches restricted to hazard ratio estimates. Theoretically, we establish the asymptotic consistency of MARS, and investigate its relative efficiency with respect to the individual participant data (IPD) meta-analysis. In simulation studies, the MARS demonstrated comparable performance to IPD meta-analysis with minor deviation from the true values, suggesting great robustness and efficiency achievable in AD meta-analysis with finite sample. Finally, we applied MARS in a meta-analysis of acute myeloid leukemia to assess the association of minimal residual disease with survival, to help respond to FDA's emerging concerns on translational use of surrogate biomarker in drug development of hematologic malignancies.

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