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

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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 & 16 more 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

Original languageEnglish
Article number757
JournalTrials
Volume23
Issue number1
DOIs
PublishedDec 2022

Bibliographical 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: © 2022, The Author(s).

King's Authors

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.

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