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The positivity assumption, or the experimental treatment assignment (ETA) assumption, is important for identifiability in causal inference. Even if the positivity assumption holds, practical violations of this assumption may jeopardize the…

Methodology · Statistics 2017-07-20 Cheng Ju , Joshua Schwab , Mark J. van der Laan

Estimating the mean counterfactual outcome under a treatment rule is a central problem in causal inference and policy evaluation. Standard estimators, including inverse probability weighting (IPW), augmented IPW (AIPW), and targeted maximum…

Methodology · Statistics 2026-05-06 Yichen Xu , Mark J. van der Laan

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

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

Robust decision making involves making decisions in the presence of uncertainty and is often used in critical domains such as healthcare, supply chains, and finance. Causality plays a crucial role in decision-making as it predicts the…

Methodology · Statistics 2025-07-23 Saideep Nannapaneni , Joseph Sakaya , Kyle Caron , Pedro HM Albuquerque , Zaid Tashman

We evaluate the performance of targeted maximum likelihood estimation (TMLE) for estimating the average treatment effect in missing data scenarios under varying levels of positivity violations. We employ model- and design-based simulations,…

Methodology · Statistics 2026-05-12 Christoph Wiederkehr , Christian Heumann , Michael Schomaker

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…

Targeted maximum likelihood estimation (TMLE) is a general method for estimating parameters in semiparametric and nonparametric models. Each iteration of TMLE involves fitting a parametric submodel that targets the parameter of interest. We…

Methodology · Statistics 2014-06-03 Iván Díaz , Michael Rosenblum

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

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

Background: Advanced methods for causal inference, such as targeted maximum likelihood estimation (TMLE), require certain conditions for statistical inference. However, in situations where there is not differentiability due to data sparsity…

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

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

With some regularity conditions maximum likelihood estimators (MLEs) always produce asymptotically optimal (in the sense of consistency, efficiency, sufficiency, and unbiasedness) estimators. But in general, the MLEs lead to non-robust…

Methodology · Statistics 2024-02-22 Chudamani Poudyal

Linear Mixed Effects (LME) models have been widely applied in clustered data analysis in many areas including marketing research, clinical trials, and biomedical studies. Inference can be conducted using maximum likelihood approach if…

Methodology · Statistics 2022-11-10 Hao Chen , Lanshan Han , Alvin Lim

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, there has been growing interest in causal machine learning estimators for quantifying subject-specific effects of a binary treatment on time-to-event outcomes. Estimation approaches have been proposed which attenuate the…

Methodology · Statistics 2026-03-30 Matthew Pryce , Karla Diaz-Ordaz , Ruth H. Keogh , Stijn Vansteelandt

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

Adaptive experimental designs have gained popularity in clinical trials and online experiments. Unlike traditional, fixed experimental designs, adaptive designs can dynamically adjust treatment randomization probabilities and other design…

Methodology · Statistics 2025-08-19 Wenxin Zhang , Mark van der Laan

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
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