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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

Randomized controlled trials (RCT) are the gold standard for evaluation of the efficacy and safety of investigational interventions. If every patient in an RCT were to adhere to the randomized treatment, one could simply analyze the…

Applications · Statistics 2020-06-08 Yongming Qu , Linda Shurzinske , Shanthi Sethuraman

The recently published ICH E9 addendum on estimands in clinical trials provides a framework for precisely defining the treatment effect that is to be estimated, but says little about estimation methods. Here we report analyses of a clinical…

Applications · Statistics 2023-09-25 Camila Olarte Parra , Rhian M. Daniel , David Wright , Jonathan W. Bartlett

To precisely define the treatment effect of interest in a clinical trial, the ICH E9 estimand addendum describes that relevant so-called intercurrent events should be identified and strategies specified to deal with them. Handling…

Methodology · Statistics 2025-02-06 Camila Olarte Parra , Rhian M. Daniel , Jonathan W. Bartlett

In medical practice, treatments are selected based on the expected causal effects on patient outcomes. Here, the gold standard for estimating causal effects are randomized controlled trials; however, such trials are costly and sometimes…

Machine Learning · Statistics 2023-01-24 Dennis Frauen , Tobias Hatt , Valentyn Melnychuk , Stefan Feuerriegel

Objective: Randomised controlled trials (RCTs) are widely considered as gold standard for assessing the effectiveness of new health interventions. When treatment non-compliance is present in RCTs, the treatment effect in the subgroup of…

Applications · Statistics 2025-03-25 Theodosios Papazoglou , Ed Waddingham , Alastair Young

The estimands framework outlined in ICH E9 (R1) describes the components needed to precisely define the effects to be estimated in clinical trials, which includes how post-baseline "intercurrent" events (IEs) are to be handled. In…

Methodology · Statistics 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

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.…

Parkinson's disease (PD) is a chronic, degenerative neurological disorder. PD cannot be prevented, slowed or cured as of today but highly effective symptomatic treatments are available. We consider relevant estimands and treatment effect…

The analysis of randomized controlled trials is often complicated by intercurrent events (IEs) -- events that occur after treatment initiation and affect either the interpretation or existence of outcome measurements. Examples include…

Methodology · Statistics 2026-04-07 Sizhu Lu , Yanyao Yi , Yongming Qu , Huayu Karen Liu , Ting Ye , Peng Ding

Constructing confidence intervals (CIs) for the average treatment effect (ATE) from patient records is crucial to assess the effectiveness and safety of drugs. However, patient records typically come from different hospitals, thus raising…

Machine Learning · Computer Science 2025-10-16 Yuxin Wang , Maresa Schröder , Dennis Frauen , Jonas Schweisthal , Konstantin Hess , Stefan Feuerriegel

This paper studies inference in randomized controlled trials with covariate-adaptive randomization when there are multiple treatments. More specifically, we study inference about the average effect of one or more treatments relative to…

Econometrics · Economics 2019-01-21 Federico A. Bugni , Ivan A. Canay , Azeem M. Shaikh

Specifications that impose constant treatment effects are common but biased, while fully flexible alternatives can be imprecise or infeasible. Under a bound on treatment effect heterogeneity, we propose a generalized ridge estimator,…

Econometrics · Economics 2026-04-07 Soonwoo Kwon , Liyang Sun

Non-adherence to assigned treatment is common in randomised controlled trials (RCTs). Recently, there has been an increased interest in estimating causal effects of treatment received, for example the so-called local average treatment…

Methodology · Statistics 2018-12-05 Karla DiazOrdaz , James Carpenter

In this paper, we introduce a unified estimator to analyze various treatment effects in causal inference, including but not limited to the average treatment effect (ATE) and the quantile treatment effect (QTE). The proposed estimator is…

Methodology · Statistics 2025-03-31 Kuan-Hsun Wu , Li-Pang Chen

In clinical trials, it is often of interest to understand the principal causal effect (PCE), the average treatment effect for a principal stratum (a subset of patients defined by the potential outcomes of one or more post-baseline…

Methodology · Statistics 2022-10-06 Yongming Qu , Ilya Lipkovich , Stephen J. Ruberg

Randomized controlled trials are the standard method for estimating causal effects, ensuring sufficient statistical power and confidence through adequate sample sizes. However, achieving such sample sizes is often challenging. This study…

Methodology · Statistics 2025-03-28 Keisuke Hanada , Masahiro Kojima

Experiments are the gold standard for causal inference. In many applications, experimental units can often be recruited or chosen sequentially, and the adaptive execution of such experiments may offer greatly improved inference of causal…

Methodology · Statistics 2023-06-14 Difan Song , Simon Mak , C. F. Jeff Wu

Randomized trials typically estimate average relative treatment effects, but decisions on the benefit of a treatment are possibly better informed by more individualized predictions of the absolute treatment effect. In case of a binary…

Methodology · Statistics 2021-08-20 J Hoogland , J IntHout , M Belias , MM Rovers , RD Riley , FE Harrell , KGM Moons , TPA Debray , JB Reitsma

In observational studies, potential unobserved confounding is a major barrier in isolating the average causal effect (ACE). In these scenarios, two main approaches are often used: confounder adjustment for causality (CAC) and instrumental…

Methodology · Statistics 2024-11-26 Roy S. Zawadzki , Daniel L. Gillen
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