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In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically…

Methodology · Statistics 2022-12-06 Waverly Wei , Maya Petersen , Mark J van der Laan , Zeyu Zheng , Chong Wu , Jingshen Wang

We offer a non-parametric plug-in estimator for an important measure of treatment effect variability and provide minimum conditions under which the estimator is asymptotically efficient. The stratum specific treatment effect function or…

Methodology · Statistics 2018-12-27 Jonathan Levy , Mark van der Laan , Alan Hubbard , Romain Pirracchio

Treatment effect heterogeneity plays an important role in many areas of causal inference and within recent years, estimation of the conditional average treatment effect (CATE) has received much attention in the statistical community. While…

Methodology · Statistics 2024-12-17 Simon Christoffer Ziersen , Torben Martinussen

We study targeted maximum likelihood estimation (TMLE) of the average treatment effect in a semiparametric regression model whose mean function is indexed by a finite-dimensional parameter, while the additive error distribution is left…

Methodology · Statistics 2026-04-20 Mijeong Kim

In this technical note we present a targeted maximum likelihood estimator (TMLE) for a previously studied target parameter that aims to transport an average treatment effect (ATE) on a clinical outcome in a source population to what the ATE…

Methodology · Statistics 2025-01-14 Mark van der Laan , Susan Gruber

Unlike the commonly used parametric regression models such as mixed models, that can easily violate the required statistical assumptions and result in invalid statistical inference, target maximum likelihood estimation allows more realistic…

Applications · Statistics 2020-06-17 Chi Zhang , Jennifer Ahern , Mark J. van der Laan

Motivated by applications in precision medicine and treatment effect heterogeneity, recent research has focused on estimating conditional average treatment effects (CATEs) using machine learning (ML). CATE estimates may represent…

Methodology · Statistics 2025-12-30 Oliver J. Hines , Karla Diaz-Ordaz , Stijn Vansteelandt

We often seek to estimate the impact of an exposure naturally occurring or randomly assigned at the cluster-level. For example, the literature on neighborhood determinants of health continues to grow. Likewise, community randomized trials…

Methodology · Statistics 2021-07-08 Laura B. Balzer , Wenjing Zheng , Mark J. van der Laan , Maya L. Petersen

Estimating heterogeneous treatment effects (HTEs) is crucial for precision medicine. While multiple studies can improve the generalizability of results, leveraging them for estimation is statistically challenging. Existing approaches often…

Methodology · Statistics 2025-12-22 Cathy Shyr , Boyu Ren , Prasad Patil , Giovanni Parmigiani

We consider Targeted Maximum Likelihood Estimation (TMLE) of weighted average treatment effects (WATEs), a class of causal estimands that reweight the covariate distribution using a specified function of the propensity score. This class…

Statistics Theory · Mathematics 2026-04-02 Yang Liu , Patrick Lopatto , Ivana Malenica

The aim of clinical effectiveness research using repositories of electronic health records is to identify what health interventions 'work best' in real-world settings. Since there are several reasons why the net benefit of intervention may…

Methodology · Statistics 2020-06-19 Jie Zhu , Blanca Gallego

The primary analysis of clinical trials in diabetes therapeutic area often involves a mixed-model repeated measure (MMRM) approach to estimate the average treatment effect for longitudinal continuous outcome, and a generalized linear mixed…

Applications · Statistics 2022-08-03 Lingjing Jiang , Michael Rosenblum , Yu Du

Targeted maximum likelihood estimators (TMLEs) are asymptotically optimal among regular, asymptotically linear estimators. In small samples, however, we may be far from "asymptopia" and not reap the benefits of optimality. Here we propose a…

Methodology · Statistics 2025-02-04 Noel Pimentel , Alejandro Schuler , Mark van der Laan

Developing tools for estimating heterogeneous treatment effects (HTE) and individualized treatment effects has been an area of active research in recent years. While these tools have proven to be useful in many contexts, a concern when…

Methodology · Statistics 2025-03-07 Mahsa Ashouri , Nicholas C. Henderson

Survival is a key metric for evaluating standards of care for people living with HIV. In resource-limited settings, high rates of loss to follow-up (LTFU) often result in underestimation of mortality when only observed deaths are…

In recent years, precision treatment strategy have gained significant attention in medical research, particularly for patient care. We propose a novel framework for estimating conditional average treatment effects (CATE) in time-to-event…

Methodology · Statistics 2024-07-29 Runjia Li , Victor B. Talisa , Chung-Chou H. Chang

In the world of targeted learning, cross-validated targeted maximum likelihood estimators, CV-TMLE [Zheng:2010aa], has a distinct advantage over TMLE [Laan:2006aa] in that one less condition is required of CV-TMLE in order to achieve…

Methodology · Statistics 2018-11-14 Jonathan Levy

Learning heterogeneous treatment effects (HTEs) is an important problem across many fields. Most existing methods consider the setting with a single treatment arm and a single outcome metric. However, in many real world domains, experiments…

Machine Learning · Computer Science 2022-06-13 Leon Yao , Caroline Lo , Israel Nir , Sarah Tan , Ariel Evnine , Adam Lerer , Alex Peysakhovich

Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times,…

The average treatment effect (ATE) is popularly used to assess the treatment effect. However, the ATE implicitly assumes a homogenous treatment effect even amongst individuals with different characteristics. In this paper, we mainly focus…

Methodology · Statistics 2016-03-10 Yunjian Yin , Lan Liu , Zhi Geng
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