Evidence map›Paper›PMID 31138317›Full record

ArticleTrials2019

This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols.

Francesca Schiavone, Riya Bathia, Krishna Letchemanan, Lindsey Masters, Claire Amos, Anna Bara, Louise Brown, Clare Gilson, Cheryl Pugh, Nafisah Atako and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 3 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 3 syntheses or guidelines pooled it.

  1. Pooled it
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  12. Improving the efficiency of clinical trials in multiple sclerosis.Multiple sclerosis (Houndmills, Basingstoke, England) · 2023
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

22 authors.

Francesca SchiavoneMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK. f.schiavone@ucl.ac.uk.ORCID http://orcid.org/0000-0002-8253-9581
Riya BathiaMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-1963-3831
Krishna LetchemananMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-7886-4779
Lindsey MastersMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-1587-8065
Claire AmosMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Anna BaraMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Louise BrownMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0003-2827-6634
Clare GilsonMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Cheryl PughMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Nafisah AtakoMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Fleur HudsonMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.
Mahesh ParmarMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0003-0166-1700
Ruth LangleyMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-9706-016X
Richard S KaplanMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-0189-8348
Chris ParkerInstitute of Cancer Research, Sutton, UK.
Gert AttardUCL Cancer Institute, University College London, London, UK.
Noel W ClarkeChristie and Royal Salford Hospital, Manchester, UK.
Silke GillessenDivision of Cancer Sciences, University of Manchester and the Christie, Manchester, UK.
Nicholas D JamesInstitute of Cancer and Genomic Sciences, University of Birmingham, Edgbaston, Birmingham, UK.ORCID http://orcid.org/0000-0002-7314-8204
Tim MaughanCancer Research UK/MRC Oxford Institute for Radiation Oncology, University of Oxford, Oxford, UK.
Matthew R SydesMRC Clinical Trials Unit at UCL, Institute of Clinical Trials and Methodology, UCL, 90 High Holborn, London, WC1V 6LJ, UK.ORCID http://orcid.org/0000-0002-9323-1371
past and present members of the STAMPEDE and FOCUS4 Trial Management Group

Funding

Astellas Pharma US 163026AstraZeneca (GB) 158046Cancer Research UK 3804Cancer Research UK A13363 and 162082Department of Health 11/100/50Efficacy and Mechanism Evaluation Programme 11/100/50Janssen Pharmaceuticals 163301Medical Research Council 171339, 171339 and 171339Medical Research Council MC_UU_12023/20Medical Research Council MC_UU_12023/24Medical Research Council MC_UU_12023/25Medical Research Council MC_UU_12023/4Novartis Pharmaceuticals UK Limited (GB) 158519
6 · The paper itself

Abstract

backgroundThere are limited research and literature on the trial management challenges encountered in running adaptive platform trials. This trial design allows both (1) the seamless addition of new research comparisons when compelling clinical and scientific research questions emerge, and (2) early stopping of accrual to individual comparisons that do not show sufficient activity without affecting other active comparisons. Adaptive platform design trials also offer many potential benefits over traditional trials, from faster time to accrual to contemporaneously recruiting multiple research comparisons, added flexibility to focus on more promising research comparisons via pre-planned interim analyses and potentially shorter time to primary results. We share here our experiences from a trial management perspective, highlighting the challenges and successes.

methodsWe evaluated the operational aspects of making changes to these adaptive platform trials and identified both common and trial-specific challenges. The operational steps and challenges linked to both the addition of new research comparisons and stopping recruitment following pre-planned interim analysis were considered in our evaluation.

resultsSpecific operational challenges in these adaptive platform protocols, additional to those in traditional two-arm trials, were identified. Key lessons are presented describing some of the solutions and considerations over conducting these trials. Careful consideration on the practicality of the protocol structure (modular versus single protocol), the longevity and continuity of trial oversight committees, and having clear clinical and scientific criteria for the addition of new research comparisons were identified as some of the most common challenges.

conclusionsUnderstanding the operational complexities associated with running adaptive platform protocols is paramount for their conduct, adaptive platform trials offer an efficient model to run randomised controlled trials and we are continuing to work to reduce further the effort required from an operational perspective.

trial registrationFOCUS4: ISRCTN Registry, ISRCTN90061546 . Registered on 16 October 2013. STAMPEDE: ISRCTN Registry, ISRCTN78818544 . Registered on 2 February 2004.

Indexed as

Clinical ProtocolsClinical Trials as TopicAdaptive Clinical Trials as TopicHumansLeadershipPeer ReviewResearch DesignAdaptive trialsMulti-arm multi stagePlatformProtocolTrial conductTrial management

Identifiers

PMID31138317
PMCPMC6540525

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.