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Recognizing the importance of real-world data (RWD) for regulatory purposes, the United States (US) Congress passed the 21st Century Cures Act1 mandating the development of Food and Drug Administration (FDA) guidance on regulatory use of…

Applications · Statistics 2023-10-19 Iván Díaz , Hana Lee , Emre Kıcıman , Mouna Akacha , Dean Follman , Debashis Ghosh

Linear mixed models are commonly used in analyzing stepped-wedge cluster randomized trials (SW-CRTs). A key consideration for analyzing a SW-CRT is accounting for the potentially complex correlation structure, which can be achieved by…

Methodology · Statistics 2024-08-21 Yongdong Ouyang , Monica Taljaard , Andrew B Forbes , Fan Li

For many rare diseases with no approved preventive interventions, promising interventions exist, yet it has been difficult to conduct a pivotal phase 3 trial that could provide direct evidence demonstrating a beneficial effect on the target…

Interpretability plays a crucial role in the application of statistical learning to estimate heterogeneous treatment effects (HTE) in complex diseases. In this study, we leverage a rule-based workflow, namely causal rule learning (CRL), to…

Machine Learning · Computer Science 2025-11-24 Ying Wu , Hanzhong Liu , Kai Ren , Shujie Ma , Xiangyu Chang

The rapid digitization of real-world data presents an unprecedented opportunity to optimize healthcare delivery and accelerate biomedical discovery. However, these data are often found in unstructured forms such as clinical notes in…

Undertaking causal inference with observational data is incredibly useful across a wide range of tasks including the development of medical treatments, advertisements and marketing, and policy making. There are two significant challenges…

Machine Learning · Statistics 2022-01-19 Matthew James Vowels , Necati Cihan Camgoz , Richard Bowden

We consider the problem of estimating the average treatment effect (ATE) when both randomized control trial (RCT) data and external real-world data (RWD) are available. We decompose the ATE estimand as the difference between a pooled-ATE…

Methodology · Statistics 2025-01-22 Mark van der Laan , Sky Qiu , Jens Magelund Tarp , Lars van der Laan

Many recent efforts center on assessing the ability of real-world evidence (RWE) generated from non-randomized, observational data to produce results compatible with those from randomized controlled trials (RCTs). One noticeable endeavor is…

Methodology · Statistics 2022-11-04 Bo Zhang

In health and social sciences, it is critically important to identify subgroups of the study population where there is notable heterogeneity of treatment effects (HTE) with respect to the population average. Decision trees have been…

Methodology · Statistics 2024-05-28 Falco J. Bargagli-Stoffi , Riccardo Cadei , Kwonsang Lee , Francesca Dominici

Real-world data, such as administrative claims and electronic health records, are increasingly used for safety monitoring and to help guide regulatory decision-making. In these settings, it is important to document analytic decisions…

Recent advances in Reinforcement Learning with Verifiable Rewards (RLVR) for multimodal large language models (MLLMs) have mainly focused on improving final answer correctness and strengthening visual grounding. However, a critical…

Computer Vision and Pattern Recognition · Computer Science 2026-03-30 Jinda Lu , Junkang Wu , Jinghan Li , Kexin Huang , Shuo Yang , Mingzhu Chen , Jiancan Wu , Kuien Liu , Xiang Wang

Recently, from the personalized medicine perspective, there has been an increased demand to identify subgroups of subjects for whom treatment is effective. Consequently, the estimation of heterogeneous treatment effects (HTE) has been…

Methodology · Statistics 2024-08-02 Ryoma Hieda , Shintaro Yuki , Kensuke Tanioka , Hiroshi Yadohisa

Randomized controlled trials (RCTs) are the gold standard for assessing drug safety and efficacy. However, RCTs have some drawbacks which have led to the use of single-arm studies to make certain internal drug development and regulatory…

Heterogeneous treatment effect (HTE) estimation is critical in medical research. It provides insights into how treatment effects vary among individuals, which can provide statistical evidence for precision medicine. While most existing…

Machine Learning · Statistics 2025-04-25 Ke Wan , Kensuke Tanioka , Toshio Shimokawa

Estimation of heterogeneous treatment effects (HTE) is of prime importance in many disciplines, ranging from personalized medicine to economics among many others. Random forests have been shown to be a flexible and powerful approach to HTE…

Methodology · Statistics 2025-10-07 Susanne Dandl , Torsten Hothorn , Heidi Seibold , Erik Sverdrup , Stefan Wager , Achim Zeileis

The identification of heterogeneous treatment effects (HTE) across subgroups is of significant interest in clinical trial analysis. Several state-of-the-art HTE estimation methods, including causal forests, apply recursive partitioning for…

Methodology · Statistics 2025-06-10 Vik Shirvaikar , Andrea Storås , Xi Lin , Chris Holmes

Stepped wedge cluster randomized controlled trials are typically analyzed using models that assume the full effect of the treatment is achieved instantaneously. We provide an analytical framework for scenarios in which the treatment effect…

Methodology · Statistics 2025-09-25 Avi Kenny , Emily Voldal , Fan Xia , Patrick J. Heagerty , James P. Hughes

Causal inference and model interpretability are gaining increasing attention, particularly in the biomedical domain. Despite recent advance, decorrelating features in nonlinear environments with human-interpretable representations remains…

Machine Learning · Computer Science 2024-11-12 Junda Wang , Weijian Li , Han Wang , Hanjia Lyu , Caroline P. Thirukumaran , Addisu Mesfin , Hong Yu , Jiebo Luo

Drug repurposing is an effective strategy to identify new uses for existing drugs, providing the quickest possible transition from bench to bedside. Existing methods for drug repurposing that mainly focus on pre-clinical information may…

Applications · Statistics 2021-04-14 Ruoqi Liu , Lai Wei , Ping Zhang

Targeted Learning is a subfield of statistics that unifies advances in causal inference, machine learning and statistical theory to help answer scientifically impactful questions with statistical confidence. Targeted Learning is driven by…