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. 2022 Sep 6;23(1):757.
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  1 , Fay Cafferty  2 , Claire Snowdon  2 , Karen Carty  3 , Joshua Savage  4 , Philip Pallmann  5 , Lucy McParland  6 , Louise Brown  7 , Lindsey Masters  7 , Francesca Schiavone  7 , Dominic Hague  7 , Stephen Townsend  7 , Claire Amos  7 , Annabelle South  7 , Kate Sturgeon  7 , Ruth Langley  7 , Timothy Maughan  8 , Nicholas James  2 , Emma Hall  2 , Sarah Kernaghan  2 , Judith Bliss  2 , Nick Turner  2 , Andrew Tutt  9 , Christina Yap  2   10 , Charlotte Firth  10 , Anthony Kong  11 , Hisham Mehanna  12 , Colin Watts  13 , Robert Hills  14 , Ian Thomas  15 , Mhairi Copland  16 , Sue Bell  17 , David Sebag-Montefiore  18 , Robert Jones  19 , Mahesh K B Parmar #  7 , Matthew R Sydes #  7
Affiliations

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

Sharon B Love et al. Trials. .

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.

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Conflict of interest statement

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.

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.

Dr Joshua Savage reports grants from Cancer Research UK, grants from The Brain Tumour Charity, during the conduct of the study; personal fees from Eli Lilly, outside the submitted work.

Dr Philip Pallmann: Health & Care Research Wales, Cancer Research UK support my institution (Centre for Trials Research) with core infrastructure funding which is used to fund time for otherwise unfunded research projects, including work on this paper.

Professor Timothy Maughan declares funds related to FOCUS4 from EME programme of MRC, Cancer Research UK and AstraZeneca.

Dr Nicholas Turner has received advisory board honoraria from Astra Zeneca, Bristol-Myers Squibb, Lilly, Merck Sharpe and Dohme, Novartis, Pfizer, Roche/Genentech, GlaxoSmithKline, Zentalis pharmaceuticals, Repare therapeutics, Arvinas and research funding from Astra Zeneca, BioRad, Pfizer, Roche/Genentech, Merck Sharpe and Dohme, Guardant Health, Invitae, Inivata, Personalis, Natera.

Professor Christina Yap reports grants from Cancer Research UK, grants from Cancer Research UK, personal fees from Celgene, personal fees from Faron Pharmaceuticals Ltd, grants and other from AstraZeneca, during the conduct of the study.

Professor Mehanna is a National Institute for Health Research (NIHR) Senior Investigator. The views expressed in this article are those of the author(s) and not necessarily those of the NIHR, or the Department of Health and Social Care.

Professor Andrew Tutt declares AstraZeneca Grant to The Institute of Cancer Research for an Externally Sponsored Collaborative Research Trial PHOENIX.

Professor Mahesh Parmar received research funding to the institution from Astellas, Clovis, Janssen, & Pfizer.

Professor Matthew Sydes received research funding to the institution from Astellas, Clovis, Janssen, Novartis, Pfizer, Sanofi-Aventis; received speaker fees from Lilly Oncology & Janssen; independent member of data monitoring committees.

All other authors have no conflicts of interests to declare for this work.

Figures

Fig. 1
Fig. 1
A platform protocol. Green plus signs show where a new arm is started during the trial, and red cross signs show when recruitment to an arm is stopped
See this image and copyright information in PMC

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