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Estimating the impact of trauma treatment protocols is complicated by the high dimensional yet finite sample nature of trauma data collected from observational studies. Viscoelastic assays are highly predictive measures of hemostasis.…

Applications · Statistics 2022-09-27 Linqing Wei , Lucy Z. Kornblith , Alan Hubbard

Asymptotic efficiency of targeted maximum likelihood estimators (TMLE) of target features of the data distribution relies on a a second order remainder being asymptotically negligible. In previous work we proposed a nonparametric MLE termed…

Statistics Theory · Mathematics 2021-07-02 Mark van der Laan , Zeyi Wang , Lars van der Laan

Clinical trials are an integral component of medical research. Trials require careful design to, for example, maintain the safety of participants, use resources efficiently and allow clinically meaningful conclusions to be drawn. Adaptive…

Methodology · Statistics 2025-07-17 James M. McGree , Antony M. Overstall , Mark Jones , Robert K. Mahar

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

The Targeted Maximum Likelihood Estimation (TMLE) statistical data analysis framework integrates machine learning, statistical theory, and statistical inference to provide a least biased, efficient and robust strategy for estimation and…

Adaptive machine learning (ML) aims to allow ML models to adapt to ever-changing environments with potential concept drift after model deployment. Traditionally, adaptive ML requires a new dataset to be manually labeled to tailor deployed…

Machine Learning · Computer Science 2024-04-10 Yutian Ren , Aaron Haohua Yen , G. P. Li

Understanding treatment effect heterogeneity has become an increasingly popular task in various fields, as it helps design personalized advertisements in e-commerce or targeted treatment in biomedical studies. However, most of the existing…

Methodology · Statistics 2024-07-12 Waverly Wei , Xinwei Ma , Jingshen Wang

Structural equation modeling (SEM) and path analysis have long been central tools for studying complex causal relationships in the social and behavioral sciences, yet their reliance on parametric assumptions can lead to biased inference…

Other Statistics · Statistics 2026-03-10 Junjie Ma , Xiaoya Zhang , Guangye He , Yuting Han , Ting Ge , Feng Ji

Consider the case that one observes a single time-series, where at each time t one observes a data record O(t) involving treatment nodes A(t), possible covariates L(t) and an outcome node Y(t). The data record at time t carries information…

Statistics Theory · Mathematics 2021-02-04 Mark J. van der Laan , Ivana Malenica

The current work is motivated by the need for robust statistical methods for precision medicine; as such, we address the need for statistical methods that provide actionable inference for a single unit at any point in time. We aim to learn…

Statistics Theory · Mathematics 2021-07-02 Ivana Malenica , Aurelien Bibaut , Mark J. van der Laan

Estimating model parameters is a crucial step in mathematical modelling and typically involves minimizing the disagreement between model predictions and experimental data. This calibration data can change throughout a study, particularly if…

Quantitative Methods · Quantitative Biology 2023-11-03 Tyler Cassidy

Adaptive designs dynamically update treatment probabilities using information accumulated during the experiment. Existing theory for causal inference from adaptive experiments primarily assumes the superpopulation framework with independent…

Methodology · Statistics 2026-02-26 Xinran Li , Anqi Zhao

Objectives: Highly flexible nonparametric estimators have gained popularity in causal inference and epidemiology. Popular examples of such estimators include targeted maximum likelihood estimators (TMLE) and double machine learning (DML).…

Methodology · Statistics 2024-08-20 Hongxiang Qiu

Adaptive sample size re-estimation, early stopping, and trial re-design at interim analyses can reduce expected sample sizes in randomised trials. Cluster randomised trials, in which groups of participants are randomly allocated to…

Methodology · Statistics 2026-03-09 Samuel I. Watson , James Martin

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…

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

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

This paper studies the generalization of the targeted minimum loss-based estimation (TMLE) framework to estimation of effects of time-varying interventions in settings where both interventions, covariates, and outcome can happen at…

Statistics Theory · Mathematics 2021-05-06 Helene C. Rytgaard , Thomas A. Gerds , Mark J. van der Laan

Revealing the underlying causal mechanisms in the real world is crucial for scientific and technological progress. Despite notable advances in recent decades, the lack of high-quality data and the reliance of traditional causal discovery…

Machine Learning · Computer Science 2026-02-17 Huaming Du , Tao Hu , Yijie Huang , Yu Zhao , Guisong Liu , Tao Gu , Gang Kou , Carl Yang

This manuscript investigates unconditional and conditional-on-stopping maximum likelihood estimators (MLEs), information measures and information loss associated with conditioning in group sequential designs (GSDs). The possibility of early…

Methodology · Statistics 2019-08-06 Sergey Tarima , Nancy Flournoy