ArticleStatistics in biopharmaceutical research2023
Hypothetical Estimands in Clinical Trials: A Unification of Causal Inference and Missing Data Methods.
Article in Statistics in biopharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- User engagement in clinical trials of digital mental health interventions: a systematic review.BMC medical research methodology · 2024Pooled it
- Estimating treatment effects in trials with outcome data truncated by death: A case study on aligning estimators with estimands.Clinical trials (London, England) · 2025Article
- Using the ICH estimand framework to improve the interpretation of treatment effects in internet interventions.NPJ digital medicine · 2025Review
- Understanding the causes and consequences of low statin adherence: evidence from UK Biobank primary care data.BMC medicine · 2025Article
- Instrumental Variable Methods to Target Hypothetical Estimands With Longitudinal Repeated Measures Data: Application to the STEP 1 Trial.Statistics in medicine · 2025Article
- Handling missing values in patient-reported outcome data in the presence of intercurrent events.BMC medical research methodology · 2025Article
- Applying the Estimands Framework to Non-Inferiority Trials: Guidance on Choice of Hypothetical Estimands for Non-Adherence and Comparison of Estimation Methods.Statistics in medicine · 2025Article
- An Example to Illustrate Randomized Trial Estimands and Estimators.The American statistician · 2025Article
- Nonlinear mixed-effects modeling as a method for causal inference to predict exposures under desired within-subject dose titration schemes.CPT: pharmacometrics & systems pharmacology · 2025Article
- Article
- Tailored guidance to apply the Estimand framework to Trials within Cohorts (TwiCs) studies.Global epidemiology · 2024Article
- Statistical methods for clinical trials interrupted by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) pandemic: A review.Statistical methods in medical research · 2024Review
- The estimands framework: a primer on the ICH E9(R1) addendum.BMJ (Clinical research ed.) · 2024Article
- Handling intercurrent events and missing data in non-inferiority trials using the estimand framework: A tuberculosis case study.Clinical trials (London, England) · 2023Article
- Defining Clinical Trial Estimands: A Practical Guide for Study Teams with Examples Based on a Psychiatric Disorder.Therapeutic innovation & regulatory science · 2023Article
- Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ICH E9 addendum introduces the term intercurrent event to refer to events that happen after treatment initiation and that can either preclude observation of the outcome of interest or affect its interpretation. It proposes five strategies for handling intercurrent events to form an estimand but does not suggest statistical methods for estimation. In this article we focus on the hypothetical strategy, where the treatment effect is defined under the hypothetical scenario in which the intercurrent event is prevented. For its estimation, we consider causal inference and missing data methods. We establish that certain "causal inference estimators" are identical to certain "missing data estimators." These links may help those familiar with one set of methods but not the other. Moreover, using potential outcome notation allows us to state more clearly the assumptions on which missing data methods rely to estimate hypothetical estimands. This helps to indicate whether estimating a hypothetical estimand is reasonable, and what data should be used in the analysis. We show that hypothetical estimands can be estimated by exploiting data after intercurrent event occurrence, which is typically not used. Supplementary materials for this article are available online.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.