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The ICH E9(R1) guideline presents a framework of estimand for clinical trials, proposes five strategies for handling intercurrent events (ICEs), and provides a comprehensive discussion and many real-life clinical examples for quantitative…

Methodology · Statistics 2025-10-20 Yixin Fang , Man Jin

The International Council for Harmonization (ICH) E9 (R1) addendum provides the estimand framework to formulate treatment effects in a clinical trial. One of the attributes of an estimand the framework describes is intercurrent events.…

Augmenting the control arm in clinical trials with external data can improve statistical power for demonstrating treatment effects. In many time-to-event outcome trials, participants are subject to truncation by death. Direct application of…

Methodology · Statistics 2025-06-24 Zehao Su , Helene C. W. Rytgaard , Henrik Ravn , Frank Eriksson

While meta-analyzing retrospective cancer patient cohorts, an investigation of differences in the expressions of target oncogenes across cancer subtypes is of substantial interest because the results may uncover novel tumorigenesis…

Methodology · Statistics 2023-07-03 Subharup Guha , David C. Christiani , S. V. Subramanian , Yi Li

We study causal effect estimation from a mixture of observational and interventional data in a confounded linear regression model with multivariate treatments. We show that the statistical efficiency in terms of expected squared error can…

Intercurrent events (ICEs) and missing values are inevitable in clinical trials of any size and duration, making it difficult to assess the treatment effect for all patients in randomized clinical trials. Defining the appropriate estimand…

Applications · Statistics 2020-06-01 Yongming Qu , Junxiang Luo , Stephen J. Ruberg

In this paper, a mixed-effect modeling scheme is proposed to construct a predictor for different features of cancer tumor. For this purpose, a set of features is extracted from two groups of patients with the same type of cancer but with…

Applications · Statistics 2018-04-13 Fatemeh Nasiri , Oscar Acosta-Tamayo

Complementary features of randomized controlled trials (RCTs) and observational studies (OSs) can be used jointly to estimate the average treatment effect of a target population. We propose a calibration weighting estimator that enforces…

Methodology · Statistics 2022-02-16 Dasom Lee , Shu Yang , Lin Dong , Xiaofei Wang , Donglin Zeng , Jianwen Cai

Time-to-event endpoints are central to evaluate treatment efficacy across many disease areas. Many trial protocols include interim analyses within group-sequential designs that control type I error via spending functions or boundary…

Methodology · Statistics 2026-01-19 Edoardo Ratti , Federico L. Perlino , Stefania Galimberti , Maria G. Valsecchi

In longitudinal studies where units are embedded in space or a social network, interference may arise, meaning that a unit's outcome can depend on treatment histories of others. The presence of interference poses significant challenges for…

Methodology · Statistics 2025-08-26 Ye Wang , Michael Jetsupphasuk

Statistical research regarding health-related quality of life (HRQoL) is a major challenge to better evaluate the impact of the treatments on their everyday life and to improve patients' care. Among the models that are used for the…

Individualized treatment rules aim to identify if, when, which, and to whom treatment should be applied. A globally aging population, rising healthcare costs, and increased access to patient-level data have created an urgent need for…

Methodology · Statistics 2019-01-04 Ying-Qi Zhao , Eric B. Laber , Yang Ning , Sumona Saha , Bruce Sands

In many applied optimization settings, parameters that define the constraints may not guarantee the best possible solution, and superior solutions might exist that are infeasible for the given parameter values. Removing such constraints,…

Optimization and Control · Mathematics 2024-07-22 Farzin Ahmadi , Todd R. McNutt , Kimia Ghobadi

We propose a framework for building patient-specific treatment recommendation models, building on the large recent literature on learning patient-level causal models and inspired by the target trial paradigm of Hernan and Robins. We focus…

Machine Learning · Statistics 2025-07-17 Rom Gutman , Shimon Sheiba , Omer Noy Klein , Naama Dekel Bird , Amit Gruber , Doron Aronson , Oren Caspi , Uri Shalit

Observational studies can play a useful role in assessing the comparative effectiveness of competing treatments. In a clinical trial the randomization of participants to treatment and control groups generally results in well-balanced groups…

In recent years, there has been a growing interest in the prediction of individualized treatment effects. While there is a rapidly growing literature on the development of such models, there is little literature on the evaluation of their…

Methodology · Statistics 2023-12-22 J Hoogland , O Efthimiou , TL Nguyen , TPA Debray

In this paper, we develop a novel logic-based approach to detecting high-level temporally extended events from timestamped data and background knowledge. Our framework employs logical rules to capture existence and termination conditions…

Artificial Intelligence · Computer Science 2026-04-24 Yvon K. Awuklu , Meghyn Bienvenu , Katsumi Inoue , Vianney Jouhet , Fleur Mougin

Observational studies provide invaluable opportunities to draw causal inference, but they may suffer from biases due to pretreatment difference between treated and control units. Matching is a popular approach to reduce observed covariate…

Methodology · Statistics 2025-09-17 Xinran Li

We study identifying and estimating the causal effect of a treatment variable on a long-term outcome using data from an observational and an experimental domain. The observational data are subject to unobserved confounding. Furthermore,…

Defining a causal estimand for a longitudinal outcome truncated by death is challenging, because the outcome may be undefined at the end of follow-up. Although a range of estimands and several estimators have been proposed, guidance on the…

Methodology · Statistics 2026-04-30 Juliette Ortholand , Young Lee , Marie-Abele C Bind