Statistical documentation for multi-disease, multi-domain platform trials: our experience with the Staphylococcus aureus Network Adaptive Platform trial - PubMed (original) (raw)

doi: 10.1186/s13063-024-08684-8.

Robert K Mahar 1 2 3, Michael Dymock 5 6, Lauren Barina 7, Marc Bonten 8 9, Asha Bowen 5 10, Matthew P Cheng 11 12, Nick Daneman 13, Anna L Goodman 14 15 16, Todd C Lee 11, Roger J Lewis 4 17, Thomas Lumley 18, Alistair R D McLean 19, Zoe McQuilten 20 21, Jocelyn Mora 7, David L Paterson 22, David J Price 23 7, Jason Roberts 24 25 26 27, Tom Snelling 5 28 29, Jonas Tverring 30 31, Steve A Webb 32, Dafna Yahav 33, Joshua S Davis 34 35, Steven Y C Tong 7 36, Julie A Marsh 5 37; SNAP Global Trial Steering Committee

Collaborators, Affiliations

Statistical documentation for multi-disease, multi-domain platform trials: our experience with the Staphylococcus aureus Network Adaptive Platform trial

Robert K Mahar et al. Trials. 2025.

Abstract

Platform trials have become widely adopted across multiple disease areas over recent years, however, guidelines for operationalising these trials have not kept pace. We outline a series of documents that summarise the statistical components, and implicit processes, of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial to provide an informal template for other researchers and reviewers of platform trials. We briefly summarise the content and role of the core protocol, statistical appendix, domain-specific appendices, simulation report, statistical implementation guides, data safety and monitoring committee (DSMC) reports, and domain-specific statistical analysis plans and final reports, and a transparent governance structure that ensures separate blinded and unblinded statistical teams. In the absence of guidelines or checklists for platform trial statistical documents, we hope to provide useful guidance to others in terms of what has worked so far for the SNAP trial, stimulate discussion, and inform a future consensus.Trial registration NCT05137119 . Registered on 30 November 2021.

© 2025. The Author(s).

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: AM is an employee of Berry Consultants, a consulting company that specialises in the design, conduct, oversight, and analysis of adaptive and platform clinical trials. MPC reports grants from the Canadian Institutes of Health Research during the conduct of the study and is supported by the Fonds de Recherche du Québec – Santé; personal fees from GEn1E Lifesciences and from Nomic Bio as a member of the scientific advisory board; as well as honoraria from AstraZeneca, Takeda, Merck, and Pfizer; research support from Cidara therapeutics, from Scynexis, Inc.; and from Amplyx Pharmaceutics during the conduct of the study but outside the submitted work. MPC is the co-founder of Kanvas Biosciences, Inc. and owns equity in the company. MPC has pending patents, including (i) methods for detecting tissue damage, graft versus host disease, and infections using cell-free DNA profiling and (ii) methods for assessing the severity and progression of SARS-CoV-2 infections using cell-free DNA pending. DLP reports that he is a consultant to the AMR Action Fund and CARB-X. RJL is the senior medical scientist and an employee of Berry Consultants, LLC, a statistical consulting firm that specialises in the design, implementation, conduct, oversight, and analysis of adaptive clinical trials, including platform trials. Where relevant, views contained within this commentary represent the authors’ own and not those of the NIHR or the UK Department of Health and Social Care.

Figures

Fig. 1

Fig. 1

Flow of statistical information in the Staphylococcus aureus Network Adaptive Platform trial. This hypothetical realisation is at its third scheduled analysis, having previously satisfied a decision rule at the second scheduled analysis leading to analyses to support a domain-specific conclusion Note: the flow of information also approximates the chronological order that the documents are produced. SAP, statistical analysis plan; SIG, statistical implementation guide; DSMC, data safety and monitoring committee. * Simulation report may be updated upon trial adaptation. † Additional domain-specific appendices may be added where required. Documents produced solely by the blinded team are unshaded, documents solely produced by the unblinded analytic team are shaded grey

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