Principles and recommendations for incorporating estimands into clinical study protocol templates
Open accessAbstract
Clinical study protocols are the foundation of good clinical studies. Prospective and multidisciplinary collaboration that pays attention to the design of all components of the study protocol can ensure that a clinical study will answer the research questions posed in a reliable manner that is meaningful for decision-makers and patients. The ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials provides a framework for clinical study planning to ensure alignment between study objectives, design, conduct, and analysis. The estimand or clinical question posed can be regarded as the backbone of the study and the clinical study protocol should reflect estimands accordingly. In practice, stakeholders are still learning how to embrace the estimand framework and how it impacts studies and study documents. In this paper, we anticipate that a protocol structure centred around estimands, or objectives rather than endpoints alone will prevail for all types of studies. To assist sponsors during this paradigm shift, this paper provides discussion and guidance for implementing the estimand framework in protocol templates.
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Recently, some trials are being designed using the estimands framework to define the research question and trial objectives.
“Recently, some trials are being designed using the estimands framework to define the research question and trial objectives.177”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [177]
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- Authors
- Lynggaard, H., Bell, J., Lösch, C., Besseghir, A., Rantell, K., Schoder, V., & Lanius, V.
- Affiliations
- Novo Nordisk (Denmark) (DK)
- UL Solutions (United States) (US)
- UCB Pharma (Belgium) (BE)
- Medicines and Healthcare products Regulatory Agency (GB)
- Bayer (Germany) (DE)
- Corresponding author
- Lynggaard, Helle
- ORCID
- Venue
- Trials
- Published
- 2022-08-19
- Volume
- 23
- Issue
- 1
- Pages
- 685-685
- ISSN
- 1745-6215 (ISSN-L)
- PMC
- PMC9389514
- OpenAlex
- W4292302476
- Cited by
- 22
- References
- 9
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 3
- FWCI
- 3.50
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Trials (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- European Federation of Pharmaceutical Industries and Associations (in collaboration with European Federation of Statisticians in the Pharmaceutical Industry)
- Boehringer Ingelheim
- 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, protocol templates, ICH E9(R1), sensitivity analysis, clinical trial design, estimand framework, research objectives, regulatory guidelines
- MeSH terms
- Data Interpretation, Statistical, Humans, Prospective Studies, Research Design, Models, Statistical
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