. 2025 Feb 11;26(1):49.

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

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

Robert K Mahar^{1

2

3}, Anna McGlothlin⁴, Michael Dymock^{5

6}, Lauren Barina⁷, Marc Bonten^{8

9}, Asha Bowen^{5

10}, Matthew P Cheng^{11

12}, Nick Daneman¹³, Anna L Goodman^{14

15

16}, Todd C Lee¹¹, Roger J Lewis^{4

17}, Thomas Lumley¹⁸, Alistair R D McLean¹⁹, Zoe McQuilten^{20

21}, Jocelyn Mora⁷, David L Paterson²², David J Price^{23

7}, Jason Roberts^{24

25

26

27}, Tom Snelling^{5

28

29}, Jonas Tverring^{30

31}, Steve A Webb³², Dafna Yahav³³, Joshua S Davis^{34

35}, Steven Y C Tong^{7

36}, Julie A Marsh^{5

37}; SNAP Global Trial Steering Committee

Collaborators, Affiliations

Collaborators

SNAP Global Trial Steering Committee:
Tom Boyles, Catherine Cosgrove, George Heriot, Marjolein Hensgens, David Lye, Susan Morpeth, Owen Robinson, Hiroki Saito, Matthew Scarborough, Sebastiaan van Hal, Genevieve Walls, Lynda Whiteway

Affiliations

¹ Centre for Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia. robert.mahar@unimelb.edu.au.
² Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia. robert.mahar@unimelb.edu.au.
³ Methods and Implementation Support for Clinical Research Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia. robert.mahar@unimelb.edu.au.
⁴ Berry Consultants, LLC, Austin, TX, USA.
⁵ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.
⁶ School of Population and Global Health, University of Western Australia, Perth, WA, Australia.
⁷ Department of Infectious Diseases, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁸ Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁹ European Clinical Research Alliance On Infectious Diseases, Utrecht, the Netherlands.
¹⁰ Perth Children's Hospital, Nedlands, WA, Australia.
¹¹ Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Canada.
¹² McGill University, Montreal, Canada.
¹³ Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
¹⁴ MRC Clinical Trials Unit at University College London, London, UK.
¹⁵ Centre for Infection Diagnostics Research at King's College, London, UK.
¹⁶ Guy's and St Thomas' NHS Foundation Trust, London, UK.
¹⁷ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹⁸ Department of Statistics, University of Auckland, Auckland, New Zealand.
¹⁹ Methods and Implementation Support for Clinical Research Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia.
²⁰ School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia.
²¹ Department of Haematology, Alfred Health, Melbourne, Australia.
²² ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²³ Centre for Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia.
²⁴ Faculty of Medicine, University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Australia.
²⁵ Herston Infectious Diseases Institute, Metro North Health, Brisbane, Australia.
²⁶ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
²⁷ Division of Anaesthesiology, Critical Care, Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Montpellier, France.
²⁸ Department of Infectious Diseases, Perth Children's Hospital, Perth, WA, Australia.
²⁹ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³⁰ Department of Infectious Diseases, Helsingborg Hospital, Helsingborg, Sweden.
³¹ Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.
³² Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
³³ Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel.
³⁴ Infection Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Sydney, Australia.
³⁵ School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
³⁶ Victorian Infectious Diseases Service, Royal Melbourne Hospital, at the, Peter Doherty Institute for Infection and Immunity , Melbourne, Australia.
³⁷ Medical School, Centre for Child Health Research, University of Western Australia, Perth, Australia.

PMID: 39934879
PMCID: PMC11817021
DOI: 10.1186/s13063-024-08684-8

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.

. 2025 Feb 11;26(1):49.

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

Authors

Collaborators

SNAP Global Trial Steering Committee:
Tom Boyles, Catherine Cosgrove, George Heriot, Marjolein Hensgens, David Lye, Susan Morpeth, Owen Robinson, Hiroki Saito, Matthew Scarborough, Sebastiaan van Hal, Genevieve Walls, Lynda Whiteway

Affiliations

¹ Centre for Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia. robert.mahar@unimelb.edu.au.
² Clinical Epidemiology and Biostatistics Unit, Murdoch Children's Research Institute, Parkville, Australia. robert.mahar@unimelb.edu.au.
³ Methods and Implementation Support for Clinical Research Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia. robert.mahar@unimelb.edu.au.
⁴ Berry Consultants, LLC, Austin, TX, USA.
⁵ Wesfarmers Centre for Vaccines and Infectious Diseases, Telethon Kids Institute, Nedlands, WA, Australia.
⁶ School of Population and Global Health, University of Western Australia, Perth, WA, Australia.
⁷ Department of Infectious Diseases, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
⁸ Julius Centre for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands.
⁹ European Clinical Research Alliance On Infectious Diseases, Utrecht, the Netherlands.
¹⁰ Perth Children's Hospital, Nedlands, WA, Australia.
¹¹ Division of Infectious Diseases and Medical Microbiology, McGill University Health Centre, Montreal, Canada.
¹² McGill University, Montreal, Canada.
¹³ Division of Infectious Diseases, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Canada.
¹⁴ MRC Clinical Trials Unit at University College London, London, UK.
¹⁵ Centre for Infection Diagnostics Research at King's College, London, UK.
¹⁶ Guy's and St Thomas' NHS Foundation Trust, London, UK.
¹⁷ David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
¹⁸ Department of Statistics, University of Auckland, Auckland, New Zealand.
¹⁹ Methods and Implementation Support for Clinical Research Hub, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, Australia.
²⁰ School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia.
²¹ Department of Haematology, Alfred Health, Melbourne, Australia.
²² ADVANCE-ID, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.
²³ Centre for Epidemiology, Melbourne School of Population and Global Health, University of Melbourne, Parkville, Australia.
²⁴ Faculty of Medicine, University of Queensland Centre for Clinical Research, University of Queensland, Brisbane, Australia.
²⁵ Herston Infectious Diseases Institute, Metro North Health, Brisbane, Australia.
²⁶ Departments of Pharmacy and Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.
²⁷ Division of Anaesthesiology, Critical Care, Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Montpellier, France.
²⁸ Department of Infectious Diseases, Perth Children's Hospital, Perth, WA, Australia.
²⁹ Sydney School of Public Health, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³⁰ Department of Infectious Diseases, Helsingborg Hospital, Helsingborg, Sweden.
³¹ Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.
³² Australian and New Zealand Intensive Care Research Centre, Monash University, Melbourne, Australia.
³³ Infectious Diseases Unit, Sheba Medical Center, Ramat-Gan, Israel.
³⁴ Infection Research Program, Hunter Medical Research Institute, New Lambton Heights, NSW, Sydney, Australia.
³⁵ School of Medicine and Public Health, University of Newcastle, Newcastle, Australia.
³⁶ Victorian Infectious Diseases Service, Royal Melbourne Hospital, at the, Peter Doherty Institute for Infection and Immunity , Melbourne, Australia.
³⁷ Medical School, Centre for Child Health Research, University of Western Australia, Perth, Australia.

PMID: 39934879
PMCID: PMC11817021
DOI: 10.1186/s13063-024-08684-8

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.

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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**
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

See this image and copyright information in PMC

References

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1. Pitre T, Cheng S, Cusano E, Khan N, Mikhail D, Leung G, et al. Methodology and design of platform trials: a meta-epidemiological study. J Clin Epidemiol. 2023;157:1–12. - DOI - PMC - PubMed
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Statistical documentation for multi-disease, multi-domain platform trials: our experience with the Staphylococcus aureus Network Adaptive Platform trial

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Figures

References

MeSH terms

Associated data

LinkOut - more resources

Full Text Sources

Medical