Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units

Sharon B. Love; Fay Cafferty; Claire Snowdon; Karen Carty; Joshua Savage; Philip Pallmann; Lucy McParland; Louise Brown; Lindsey Masters; Francesca Schiavone; Dominic Hague; Stephen Townsend; Claire Amos; Annabelle South; Kate Sturgeon; Ruth Langley; Timothy Maughan; Nicholas James; Emma Hall; Sarah Kernaghan; Judith Bliss; Nick Turner; Andrew Tutt; Christina Yap; Charlotte Firth; Anthony Kong; Hisham Mehanna; Colin Watts; Robert Hills; Ian Thomas; Mhairi Copland; Sue Bell; David Sebag-Montefiore; Robert Jones; Mahesh K.B. Parmar; Matthew R. Sydes

doi:10.1186/s13063-022-06680-4

Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units

Sharon B. Love^*, Fay Cafferty, Claire Snowdon, Karen Carty, Joshua Savage, Philip Pallmann, Lucy McParland, Louise Brown, Lindsey Masters, Francesca Schiavone, Dominic Hague, Stephen Townsend, Claire Amos, Annabelle South, Kate Sturgeon, Ruth Langley, Timothy Maughan, Nicholas James, Emma Hall, Sarah KernaghanJudith Bliss, Nick Turner, Andrew Tutt, Christina Yap, Charlotte Firth, Anthony Kong, Hisham Mehanna, Colin Watts, Robert Hills, Ian Thomas, Mhairi Copland, Sue Bell, David Sebag-Montefiore, Robert Jones, Mahesh K.B. Parmar, Matthew R. Sydes

^*Corresponding author for this work

Comprehensive Cancer Centre

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Background: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations. Methods: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols. Results: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement. Discussion: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.

Original language	English
Article number	757
Journal	Trials
Volume	23
Issue number	1
DOIs	https://doi.org/10.1186/s13063-022-06680-4
Publication status	Published - Dec 2022

Keywords

Basket trials
Complex innovative designs
Methodology
Multi-arm multi-stage trials
Platform protocols
Stratified medicine
Trial conduct
Umbrella trials

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10.1186/s13063-022-06680-4

Cite this

Love, S. B., Cafferty, F., Snowdon, C., Carty, K., Savage, J., Pallmann, P., McParland, L., Brown, L., Masters, L., Schiavone, F., Hague, D., Townsend, S., Amos, C., South, A., Sturgeon, K., Langley, R., Maughan, T., James, N., Hall, E., ... Sydes, M. R. (2022). Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units. Trials, 23(1), Article 757. https://doi.org/10.1186/s13063-022-06680-4

@article{d39d57de87eb446684b734837a183aee,

title = "Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units",

abstract = "Background: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations. Methods: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols. Results: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement. Discussion: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.",

keywords = "Basket trials, Complex innovative designs, Methodology, Multi-arm multi-stage trials, Platform protocols, Stratified medicine, Trial conduct, Umbrella trials",

author = "Love, {Sharon B.} and Fay Cafferty and Claire Snowdon and Karen Carty and Joshua Savage and Philip Pallmann and Lucy McParland and Louise Brown and Lindsey Masters and Francesca Schiavone and Dominic Hague and Stephen Townsend and Claire Amos and Annabelle South and Kate Sturgeon and Ruth Langley and Timothy Maughan and Nicholas James and Emma Hall and Sarah Kernaghan and Judith Bliss and Nick Turner and Andrew Tutt and Christina Yap and Charlotte Firth and Anthony Kong and Hisham Mehanna and Colin Watts and Robert Hills and Ian Thomas and Mhairi Copland and Sue Bell and David Sebag-Montefiore and Robert Jones and Parmar, {Mahesh K.B.} and Sydes, {Matthew R.}",

note = "Funding Information: The Cancer Research UK Clinical Trials Unit (CRCTU) is supported by a core programme grant from Cancer Research UK grant number C22436/A25354 which funded the input from Christina Yap and Charlotte Firth. Funding Information: Dr Fay Cafferty reports receipt of research grants for the Add-Aspirin trial from Cancer Research UK and the National Institute of Health Research, as well as study drug provision from Bayer Pharmaceuticals. Funding Information: Dr Claire Snowdon, Professor Judith Bliss, Professor Emma Hall and Dr Sarah Kernaghan reports grants from Cancer Research UK, grants and non-financial support from AstraZeneca, grants and non-financial support from Puma Biotechnology, during the conduct of the study. Funding Information: Sharon Love Matthew R Sydes, Annabelle South, Fay Cafferty, Lindsey Masters, Francesca Schiavone, Stephen Townsend, Claire Amos, and Kate Sturgeon were funded by MRC grant MC_UU_00004/08. Ruth Langley, Mahesh Parmar, and Louise Brown by MC_UU_00004/01 MC_UU_00004/02. Funding Information: Thank you to all of the funders for these trials including Cancer Research UK grant number C471 /A15015, CRUK_A12459, https://www.cancerresearchuk.org/ , Medical Research Council (MRC_MC_UU_12023/25), https://www.ukri.org/councils/mrc/ , Swiss Group for Clinical Cancer Research, https://www.sakk.ch/ , Cancer Research UK grant CRUK/C19677/A17226). Cancer Research UK grant number C471/A15015, The National Institute for Health Research Health Technology Assessment Programme (project reference 12/01/38). Funding Information: The Centre for Trials Research receives infrastructure funding from Health and Care Research Wales and Cancer Research UK which funded the input from Philip Pallmann and Ian Thomas. Funding Information: Researchers need to recognise that funding may need to be sought from multiple sources across the life of a platform protocol and this multiple collaboration will take more time than if there was one funder. Cancer examples (e.g. CompARE, FLAIR, STAMPEDE, plasmaMATCH, AML LI-1) started with both a research trial infrastructure grant from a cancer charity (Cancer Research UK or Blood Cancer UK) and support in some form from an industry partner, e.g. FLAIR with Jansen; STAMPEDE with Pfizer, Novartis and Sanofi; plasmaMATCH with AstraZeneca and Puma; AML LI-1 Cyclacel, Ambit and Sunesis), together with flexible use of core MRC funding for STAMPEDE. Each new comparisons must come with sufficient funding and include a contribution to fund the overall infrastructure. For example, new comparisons in these trials have included collaboration with and support from Abbvie, Astellas, AstraZeneca, Bayer BCTI, Synta, Cell Therapeutics, Karyopharm, and Janssen, demonstrating that key international pharmaceutical companies are open to supporting comparisons within ongoing platform protocols. Funding Information: Thank you to all members of AddAspirin, AML LI-1, ATLANTIS, Brain Matrix, CompARE, FLAIR, FOCUS4, National Lung Matrix Trial, OCTOPUS, PHOENIX, plasmaMATCH, PLATO, PrecisionPanc, STAMPEDE, and TASTER who have contributed examples and shared these lessons. Thank you to Professor Andrew Tutt (CI of PHOENIX), Professor Garry Middleton (CI National Lung Matrix), Professor Mike Dennis and Dr Thomas Powles (CI AML LI-1), Professor Peter Hillmen (CI FLAIR), Professor Andrew Biankin (CI PrecisionPanc), Dr Susana Banerjee (CI OCTOPUS), and Professor Richard Wilson (co-CI FOCUS4, CI Add Aspirin colorectal trial). Thank you to Andrea Harkin and Caroline Kelly for their comments on the paper. Thank you to all of the funders for these trials including Cancer Research UK grant number C471 /A15015, CRUK_A12459, https://www.cancerresearchuk.org/ , Medical Research Council (MRC_MC_UU_12023/25), https://www.ukri.org/councils/mrc/ , Swiss Group for Clinical Cancer Research, https://www.sakk.ch/ , Cancer Research UK grant CRUK/C19677/A17226). Cancer Research UK grant number C471/A15015, The National Institute for Health Research Health Technology Assessment Programme (project reference 12/01/38). Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13063-022-06680-4",

language = "English",

volume = "23",

journal = "Trials",

issn = "1745-6215",

publisher = "BioMed Central",

number = "1",

}

Love, SB, Cafferty, F, Snowdon, C, Carty, K, Savage, J, Pallmann, P, McParland, L, Brown, L, Masters, L, Schiavone, F, Hague, D, Townsend, S, Amos, C, South, A, Sturgeon, K, Langley, R, Maughan, T, James, N, Hall, E, Kernaghan, S, Bliss, J, Turner, N, Tutt, A, Yap, C, Firth, C, Kong, A, Mehanna, H, Watts, C, Hills, R, Thomas, I, Copland, M, Bell, S, Sebag-Montefiore, D, Jones, R, Parmar, MKB & Sydes, MR 2022, 'Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units', Trials, vol. 23, no. 1, 757. https://doi.org/10.1186/s13063-022-06680-4

TY - JOUR

T1 - Practical guidance for running late-phase platform protocols for clinical trials

T2 - lessons from experienced UK clinical trials units

AU - Love, Sharon B.

AU - Cafferty, Fay

AU - Snowdon, Claire

AU - Carty, Karen

AU - Savage, Joshua

AU - Pallmann, Philip

AU - McParland, Lucy

AU - Brown, Louise

AU - Masters, Lindsey

AU - Schiavone, Francesca

AU - Hague, Dominic

AU - Townsend, Stephen

AU - Amos, Claire

AU - South, Annabelle

AU - Sturgeon, Kate

AU - Langley, Ruth

AU - Maughan, Timothy

AU - James, Nicholas

AU - Hall, Emma

AU - Kernaghan, Sarah

AU - Bliss, Judith

AU - Turner, Nick

AU - Tutt, Andrew

AU - Yap, Christina

AU - Firth, Charlotte

AU - Kong, Anthony

AU - Mehanna, Hisham

AU - Watts, Colin

AU - Hills, Robert

AU - Thomas, Ian

AU - Copland, Mhairi

AU - Bell, Sue

AU - Sebag-Montefiore, David

AU - Jones, Robert

AU - Parmar, Mahesh K.B.

AU - Sydes, Matthew R.

N1 - Funding Information: The Cancer Research UK Clinical Trials Unit (CRCTU) is supported by a core programme grant from Cancer Research UK grant number C22436/A25354 which funded the input from Christina Yap and Charlotte Firth. Funding Information: Dr Fay Cafferty reports receipt of research grants for the Add-Aspirin trial from Cancer Research UK and the National Institute of Health Research, as well as study drug provision from Bayer Pharmaceuticals. Funding Information: Dr Claire Snowdon, Professor Judith Bliss, Professor Emma Hall and Dr Sarah Kernaghan reports grants from Cancer Research UK, grants and non-financial support from AstraZeneca, grants and non-financial support from Puma Biotechnology, during the conduct of the study. Funding Information: Sharon Love Matthew R Sydes, Annabelle South, Fay Cafferty, Lindsey Masters, Francesca Schiavone, Stephen Townsend, Claire Amos, and Kate Sturgeon were funded by MRC grant MC_UU_00004/08. Ruth Langley, Mahesh Parmar, and Louise Brown by MC_UU_00004/01 MC_UU_00004/02. Funding Information: Thank you to all of the funders for these trials including Cancer Research UK grant number C471 /A15015, CRUK_A12459, https://www.cancerresearchuk.org/ , Medical Research Council (MRC_MC_UU_12023/25), https://www.ukri.org/councils/mrc/ , Swiss Group for Clinical Cancer Research, https://www.sakk.ch/ , Cancer Research UK grant CRUK/C19677/A17226). Cancer Research UK grant number C471/A15015, The National Institute for Health Research Health Technology Assessment Programme (project reference 12/01/38). Funding Information: The Centre for Trials Research receives infrastructure funding from Health and Care Research Wales and Cancer Research UK which funded the input from Philip Pallmann and Ian Thomas. Funding Information: Researchers need to recognise that funding may need to be sought from multiple sources across the life of a platform protocol and this multiple collaboration will take more time than if there was one funder. Cancer examples (e.g. CompARE, FLAIR, STAMPEDE, plasmaMATCH, AML LI-1) started with both a research trial infrastructure grant from a cancer charity (Cancer Research UK or Blood Cancer UK) and support in some form from an industry partner, e.g. FLAIR with Jansen; STAMPEDE with Pfizer, Novartis and Sanofi; plasmaMATCH with AstraZeneca and Puma; AML LI-1 Cyclacel, Ambit and Sunesis), together with flexible use of core MRC funding for STAMPEDE. Each new comparisons must come with sufficient funding and include a contribution to fund the overall infrastructure. For example, new comparisons in these trials have included collaboration with and support from Abbvie, Astellas, AstraZeneca, Bayer BCTI, Synta, Cell Therapeutics, Karyopharm, and Janssen, demonstrating that key international pharmaceutical companies are open to supporting comparisons within ongoing platform protocols. Funding Information: Thank you to all members of AddAspirin, AML LI-1, ATLANTIS, Brain Matrix, CompARE, FLAIR, FOCUS4, National Lung Matrix Trial, OCTOPUS, PHOENIX, plasmaMATCH, PLATO, PrecisionPanc, STAMPEDE, and TASTER who have contributed examples and shared these lessons. Thank you to Professor Andrew Tutt (CI of PHOENIX), Professor Garry Middleton (CI National Lung Matrix), Professor Mike Dennis and Dr Thomas Powles (CI AML LI-1), Professor Peter Hillmen (CI FLAIR), Professor Andrew Biankin (CI PrecisionPanc), Dr Susana Banerjee (CI OCTOPUS), and Professor Richard Wilson (co-CI FOCUS4, CI Add Aspirin colorectal trial). Thank you to Andrea Harkin and Caroline Kelly for their comments on the paper. Thank you to all of the funders for these trials including Cancer Research UK grant number C471 /A15015, CRUK_A12459, https://www.cancerresearchuk.org/ , Medical Research Council (MRC_MC_UU_12023/25), https://www.ukri.org/councils/mrc/ , Swiss Group for Clinical Cancer Research, https://www.sakk.ch/ , Cancer Research UK grant CRUK/C19677/A17226). Cancer Research UK grant number C471/A15015, The National Institute for Health Research Health Technology Assessment Programme (project reference 12/01/38). Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - Background: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations. Methods: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols. Results: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement. Discussion: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.

AB - Background: Late-phase platform protocols (including basket, umbrella, multi-arm multi-stage (MAMS), and master protocols) are generally agreed to be more efficient than traditional two-arm clinical trial designs but are not extensively used. We have gathered the experience of running a number of successful platform protocols together to present some operational recommendations. Methods: Representatives of six UK clinical trials units with experience in running late-phase platform protocols attended a 1-day meeting structured to discuss various practical aspects of running these trials. We report and give guidance on operational aspects which are either harder to implement compared to a traditional late-phase trial or are specific to platform protocols. Results: We present a list of practical recommendations for trialists intending to design and conduct late-phase platform protocols. Our recommendations cover the entire life cycle of a platform trial: from protocol development, obtaining funding, and trial set-up, to a wide range of operational and regulatory aspects such as staffing, oversight, data handling, and data management, to the reporting of results, with a particular focus on communication with trial participants and stakeholders as well as public and patient involvement. Discussion: Platform protocols enable many questions to be answered efficiently to the benefit of patients. Our practical lessons from running platform trials will support trial teams in learning how to run these trials more effectively and efficiently.

KW - Basket trials

KW - Complex innovative designs

KW - Methodology

KW - Multi-arm multi-stage trials

KW - Platform protocols

KW - Stratified medicine

KW - Trial conduct

KW - Umbrella trials

UR - http://www.scopus.com/inward/record.url?scp=85137309861&partnerID=8YFLogxK

U2 - 10.1186/s13063-022-06680-4

DO - 10.1186/s13063-022-06680-4

M3 - Article

C2 - 36068599

AN - SCOPUS:85137309861

SN - 1745-6215

VL - 23

JO - Trials

JF - Trials

IS - 1

M1 - 757

ER -

Practical guidance for running late-phase platform protocols for clinical trials: lessons from experienced UK clinical trials units

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