The estimands framework: a primer on the ICH E9(R1) addendum
Open accessAbstract
Estimands can be used in studies of healthcare interventions to clarify the interpretation of treatment effects. The addendum to the ICH E9 harmonised guideline on statistical principles for clinical trials (ICH E9(R1)) describes a framework for using estimands as part of a study. This paper provides an overview of the estimands framework, as outlined in the addendum, with the aim of explaining why estimands are beneficial; clarifying the terminology being used; and providing practical guidance on using estimands to decide the appropriate study design, data collection, and estimation methods. This article illustrates how to use the estimands framework by applying it to an ongoing trial in emergency bowel surgery. Estimands can be a useful way of clarifying the exact research question being evaluated in a study, both to avoid misinterpretation and to ensure that study methods are aligned to the overall study objectives.
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The estimands framework provides a structured description of the treatment effect in an attempt to bring clarity to specifying the research question.
“The estimands framework provides a structured description of the treatment effect in an attempt to bring clarity to specifying the research question, which can be used to guide the study design, data collection, and statistical analysis methods.”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [169]
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SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials
Hróbjartsson, A., Boutron, I., Hopewell, S., Moher, D., Schulz, K. F., Collins, G. S., Tunn, R., Aggarwal, R., Berkwits, M., Berlin, J. A., et al. (2025) · BMJ · doi:10.1136/bmj-2024-081660 · Cited by 171 · see citing works
Self-citation
- Authors
- Kahan, B. C., Hindley, J., Edwards, M., Cro, S., & Morris, T. P.
- Affiliations
- MRC Clinical Trials Unit at UCL (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- Imperial College London (GB)
- Corresponding author
- Kahan, Brennan C
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2024-01-23
- Volume
- 384
- Pages
- e076316
- ISSN
- 1756-1833 (ISSN-L)
- PMC
- PMC10802140
- OpenAlex
- W4391133908
- Cited by
- 180
- References
- 65
- Citations by year
- 2026: 84 · 2025: 72 · 2024: 24
- FWCI
- 61.53
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- BMJ (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion, cc-by)
- HighWire Press Open Archive (submittedVersion)
- Funders
- National Institute for Health and Care Research (15/80/54, NIHR300593)
- Medical Research Council (MC_UU_00004/09, MC_UU_00004/07, MR/S014357/1)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- estimands, treatment effect interpretation, research design, estimation methods, clinical trial interpretation
- MeSH terms
- Humans, Research Design, Models, Statistical
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