Guidelines for the Content of Statistical Analysis Plans in Clinical Trials
Open accessAbstract
Importance: While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility. Objective: To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders. Design: Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration-registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials. Findings: No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42% (n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items. Conclusions and Relevance: Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials.
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Details of all statistical analyses are often reported in a full statistical analysis plan-a document that accompanies a trial protocol.
“Details of all statistical analyses are often reported in a full statistical analysis plan—a document that accompanies a trial protocol.71”
From SPIRIT 2025 explanation and elaboration: updated guideline for protocols of randomised trials (2025) · cites this paper as [71]
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- Authors
- Gamble, C., Krishan, A., Stocken, D., Lewis, S., Juszczak, E., Doré, C., Williamson, P. R., Altman, D. G., Montgomery, A., Lim, P., Berlin, J., Senn, S., Day, S., Barbachano, Y., & Loder, E.
- Affiliations
- University of Liverpool (GB)
- University of Leeds (GB)
- University of Edinburgh (GB)
- University of Oxford (GB)
- MRC Clinical Trials Unit at UCL (GB)
- University of Nottingham (GB)
- Janssen Research & Development (United States) (US)
- Johnson & Johnson (United States) (US)
- Luxembourg Institute of Health (LU)
- Clinical Trials Consulting & Training Limited, Buckingham, England
- Medicines and Healthcare Products Regulatory Agency, London, England
- BMJ Group (United Kingdom) (GB)
- Corresponding author
- Gamble, Carrol
- ORCID
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2017-12-19
- Volume
- 318
- Issue
- 23
- Pages
- 2337
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2778174446
- Cited by
- 536
- References
- 16
- Citations by year
- 2026: 42 · 2025: 73 · 2024: 98 · 2023: 60 · 2022: 77 · 2021: 55 · 2020: 86 · 2019: 30 · 2018: 14 · 2017: 1
- FWCI
- 24.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Repository@Nottingham (University of Nottingham) (publishedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
- Repository@Nottingham (University of Nottingham) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Funders
- United Kingdom Clinical Research Collaboration
- Cancer Research UK (16895)
- Medical Research Council (MR/L004933/1, MR/L004933/2, MC_UU_12023/21, MR/K025635/1)
- Topics
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Social Sciences › Decision Sciences › Statistics, Probability and Uncertainty › Meta-analysis and systematic reviews
- Social Sciences › Sociology and Political Science › Delphi Technique in Research
- Keywords
- statistical analysis plan, clinical trials, reproducibility, reporting guidelines, CONSORT, alcoholic beverages, clinical trial registration, Delphi consensus, expert consensus
- MeSH terms
- Clinical Trials as Topic, Data Interpretation, Statistical, Delphi Technique, Statistics as Topic
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