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

Abstract:

BACKGROUND: There 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.

METHODS: We 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.

RESULTS: Specific 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.

CONCLUSIONS: Understanding 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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1186/s13063-019-3216-8

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Role:
Author
ORCID:
0000-0002-8253-9581
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Role:
Author
ORCID:
0000-0002-1963-3831
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Role:
Author
ORCID:
0000-0002-7886-4779
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Role:
Author
ORCID:
0000-0002-1587-8065



Publisher:
BioMed Central
Journal:
Trials More from this journal
Volume:
20
Issue:
1
Article number:
264
Publication date:
2019-05-09
Acceptance date:
2019-01-09
DOI:
EISSN:
1745-6215
ISSN:
1745-6215
Pmid:
31138317


Language:
English
Keywords:
Pubs id:
pubs:1004606
UUID:
uuid:89e5e6d8-76fa-4728-93ed-3db7d7ae96c7
Local pid:
pubs:1004606
Source identifiers:
1004606
Deposit date:
2019-06-15

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