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An individualized treatment rule (ITR) tailors treatments to a patient's specific characteristics. However, randomized controlled trials (RCTs) are often underpowered to detect the treatment effect heterogeneity needed for reliable ITR…

Methodology · Statistics 2026-04-14 Yuan Bian , Donglin Zeng , Hyun-Joon Yang , Leanne M. Williams , Yuanjia Wang

Recently, causal inference under interference has gained increasing attention in the literature. In this paper, we focus on randomized designs for estimating the total treatment effect (TTE), defined as the average difference in potential…

Methodology · Statistics 2024-08-29 Changhao Shi , Haoyu Yang , Yichen Qin , Yang Li

Randomized controlled trials (RCTs) often include subgroup analyses to assess whether treatment effects vary across pre-specified patient populations. However, these analyses frequently suffer from small sample sizes which limit the power…

Reliable causal effect estimation from observational data requires adjustment for confounding and sufficient overlap in covariate distributions between treatment groups. However, in high-dimensional settings, lack of overlap often inflates…

Methodology · Statistics 2025-03-21 Linying Yang , Robin J. Evans

Quantifying the heterogeneity of treatment effect is important for understanding how a commercial product or medical treatment affects different population subgroups. While much of treatment effect heterogeneity analysis focuses on the…

We consider the estimation of the average treatment effect in the treated as a function of baseline covariates, where there is a valid (conditional) instrument. We describe two doubly robust (DR) estimators: a locally efficient g-estimator,…

Methodology · Statistics 2019-06-11 Karla DiazOrdaz , Rhian Daniel , Noemi Kreif

A targeted learning (TL) framework is developed to estimate the difference in the restricted mean survival time (RMST) for a clinical trial with time-to-event outcomes. The approach starts by defining the target estimand as the RMST…

Methodology · Statistics 2026-01-21 Man Jin , Yixin Fang

Data from both a randomized trial and an observational study are sometimes simultaneously available for evaluating the effect of an intervention. The randomized data typically allows for reliable estimation of average treatment effects but…

Methodology · Statistics 2021-12-01 David Cheng , Tianxi Cai

Missing data is unavoidable in longitudinal clinical trials, and outcomes are not always normally distributed. In the presence of outliers or heavy-tailed distributions, the conventional multiple imputation with the mixed model with…

Methodology · Statistics 2022-03-22 Siyi Liu , Yilong Zhang , Gregory T Golm , Guanghan , Liu , Shu Yang

There is growing interest in using machine learning (ML) to support clinical diagnosis, but most approaches rely on static, fully observed datasets and fail to reflect the sequential, resource-aware reasoning clinicians use in practice.…

Artificial Intelligence · Computer Science 2025-11-18 Silas Ruhrberg Estévez , Nicolás Astorga , Mihaela van der Schaar

Current Targeted Maximum Likelihood Estimation (TMLE) methods used to analyze time-to-event data estimate the survival probability for each time point separately, which result in estimates that are not necessarily monotone. In this paper,…

Methodology · Statistics 2019-06-14 Weixin Cai , Mark J. van der Laan

Most clinical trials involve the comparison of a new treatment to a control arm (e.g., the standard of care) and the estimation of a treatment effect. External data, including historical clinical trial data and real-world observational…

Methodology · Statistics 2021-03-17 Tianjian Zhou , Yuan Ji

Covariate adjustment is widely recommended to improve statistical efficiency in randomized clinical trials (RCTs), yet empirical evidence comparing available strategies remains limited. This lack of real-world evaluation leaves unresolved…

Applications · Statistics 2026-02-03 Yulin Shao , Liangbo Lyu , Menggang Yu , Bingkai Wang

Background: Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without…

The randomization inference literature studying randomized controlled trials (RCTs) assumes that units' potential outcomes are deterministic. This assumption is unlikely to hold, as stochastic shocks may take place during the experiment. In…

Econometrics · Economics 2022-12-15 Antoine Deeb , Clément de Chaisemartin

Introduction: Increasing interest in real-world evidence has fueled the development of study designs incorporating real-world data (RWD). Using the Causal Roadmap, we specify three designs to evaluate the difference in risk of major adverse…

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…

Methodology · Statistics 2021-04-20 Wennan Chang , Xinyu Zhou , Yong Zang , Chi Zhang , Sha Cao

Kernel matching is a widely used technique for estimating treatment effects, particularly valuable in observational studies where randomized controlled trials are not feasible. While kernel-matching approaches have demonstrated practical…

Methodology · Statistics 2025-12-11 Chong Ding , Zheng Li , Hon Keung Tony Ng , Wei Gao

Clinical risk prediction models are regularly updated as new data, often with additional covariates, become available. We propose CARE (Convex Aggregation of relative Risk Estimators) as a general approach for combining existing "external"…

Observational epidemiological studies commonly seek to estimate the causal effect of an exposure on an outcome. Adjustment for potential confounding bias in modern studies is challenging due to the presence of high-dimensional confounding,…

Methodology · Statistics 2025-08-29 Susan Ellul , Stijn Vansteelandt , John B. Carlin , Margarita Moreno-Betancur
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