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The estimand framework proposes different strategies to address intercurrent events. The treatment policy strategy seems to be the most favoured as it is closely aligned with the pre-addendum intention-to-treat principle. All data for all…

统计方法学 · 统计学 2025-07-21 Sunita Rehal , Nicky Best , Sarah Watts , Thomas Drury

Estimands using the treatment policy strategy for addressing intercurrent events are common in Phase III clinical trials. One estimation approach for this strategy is retrieved dropout whereby observed data following an intercurrent event…

The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E9 (R1) Addendum provides a framework for defining estimands in clinical trials. Treatment policy strategy is the mostly used…

应用统计 · 统计学 2024-10-10 Rong Liu , Yongming Qu

When treatment policy estimands are of interest, clinical trials often attempt to collect patient data after intercurrent events (ICEs), although such data are often limited. Retrieved dropout imputation methods, which use pre-ICE and…

统计方法学 · 统计学 2026-03-31 Brendah Nansereko , Marcel Wolbers , James R. Carpenter , Jonathan W. Bartlett

We provide guidance on multiple imputation of missing at random treatments in observational studies. Specifically, analysts should account for both covariates and outcomes, i.e., not just use propensity scores, when imputing the missing…

统计方法学 · 统计学 2025-01-23 Joseph Feldman , Jerome P. Reiter

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…

统计方法学 · 统计学 2023-08-28 Thomas Drury , Juan J Abellan , Nicky Best , Ian R. White

Multiple imputation is a straightforward method for handling missing data in a principled fashion. This paper presents an overview of multiple imputation, including important theoretical results and their practical implications for…

统计方法学 · 统计学 2018-01-15 Jared S. Murray

Return-to-baseline is an important method to impute missing values or unobserved potential outcomes when certain hypothetical strategies are used to handle intercurrent events in clinical trials. Current return-to-baseline approaches seen…

统计方法学 · 统计学 2021-11-19 Yongming Qu , Biyue Dai

Multiple imputation is a highly recommended technique to deal with missing data, but the application to longitudinal datasets can be done in multiple ways. When a new wave of longitudinal data arrives, we can treat the combined data of…

统计方法学 · 统计学 2026-05-18 X. M. Kavelaars , S. van Buuren , J. R. van Ginkel

Missing data is a systemic problem in practical scenarios that causes noise and bias when estimating treatment effects. This makes treatment effect estimation from data with missingness a particularly tricky endeavour. A key reason for this…

机器学习 · 统计学 2023-02-27 Jeroen Berrevoets , Fergus Imrie , Trent Kyono , James Jordon , Mihaela van der Schaar

Missing data are often dealt with multiple imputation. A crucial part of the multiple imputation process is selecting sensible models to generate plausible values for incomplete data. A method based on posterior predictive checking is…

统计计算 · 统计学 2026-05-14 Mingyang Cai , Stef van Buuren , Gerko Vink

The estimand framework provides guidance on handling intercurrent events, such as treatment discontinuation, in the analysis of clinical trial responses. Under ICH E9(R1), the treatment policy (TP) strategy incorporates post-discontinuation…

统计方法学 · 统计学 2026-04-07 Myeongjong Kang , Sangyoon Yi

We present a framework for generating multiple imputations for continuous data when the missing data mechanism is unknown. Imputations are generated from more than one imputation model in order to incorporate uncertainty regarding the…

应用统计 · 统计学 2013-01-14 Juned Siddique , Ofer Harel , Catherine M. Crespi

Background: Existing guidelines for handling missing data are generally not consistent with the goals of prediction modelling, where missing data can occur at any stage of the model pipeline. Multiple imputation (MI), often heralded as the…

统计方法学 · 统计学 2022-06-27 Rose Sisk , Matthew Sperrin , Niels Peek , Maarten van Smeden , Glen P. Martin

Data collected in clinical trials are often composed of multiple types of variables. For example, laboratory measurements and vital signs are longitudinal data of continuous or categorical variables, adverse events may be recurrent events,…

统计方法学 · 统计学 2023-01-12 Tuo Wang , Rachel Zilinskas , Ying Li , Yongming Qu

Longitudinal studies are frequently used in medical research and involve collecting repeated measures on individuals over time. Observations from the same individual are invariably correlated and thus an analytic approach that accounts for…

Missing data is a common challenge when analyzing epidemiological data, and imputation is often used to address this issue. Here, we investigate the scenario where a covariate used in an analysis has missingness and will be imputed. There…

统计方法学 · 统计学 2024-03-04 Lucy D'Agostino McGowan , Sarah C. Lotspeich , Staci A. Hepler

Case-cohort studies are conducted within cohort studies, wherein collection of exposure data is limited to a subset of the cohort, leading to a large proportion of missing data by design. Standard analysis uses inverse probability weighting…

Multiple imputation has become one of the standard methods in drawing inferences in many incomplete data applications. Applications of multiple imputation in relatively more complex settings, such as high-dimensional clustered data, require…

统计方法学 · 统计学 2025-04-08 Qiushuang Li , Recai Yucel

Analysis of longitudinal randomised controlled trials is frequently complicated because patients deviate from the protocol. Where such deviations are relevant for the estimand, we are typically required to make an untestable assumption…

统计方法学 · 统计学 2018-05-16 Suzie Cro , James R Carpenter , Michael G Kenward
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