This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols.
Adaptive trials
Multi-arm multi stage
Platform
Protocol
Trial conduct
Trial management
Journal
Trials
ISSN: 1745-6215
Titre abrégé: Trials
Pays: England
ID NLM: 101263253
Informations de publication
Date de publication:
29 May 2019
29 May 2019
Historique:
received:
10
08
2018
accepted:
19
01
2019
entrez:
30
5
2019
pubmed:
30
5
2019
medline:
24
12
2019
Statut:
epublish
Résumé
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. 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. 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. 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. FOCUS4: ISRCTN Registry, ISRCTN90061546 . Registered on 16 October 2013. ISRCTN Registry, ISRCTN78818544 . Registered on 2 February 2004.
Sections du résumé
BACKGROUND
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
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
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
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.
TRIAL REGISTRATION
BACKGROUND
FOCUS4: ISRCTN Registry, ISRCTN90061546 . Registered on 16 October 2013.
STAMPEDE
UNASSIGNED
ISRCTN Registry, ISRCTN78818544 . Registered on 2 February 2004.
Identifiants
pubmed: 31138317
doi: 10.1186/s13063-019-3216-8
pii: 10.1186/s13063-019-3216-8
pmc: PMC6540525
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
264Subventions
Organisme : Department of Health
ID : 11/100/50
Pays : United Kingdom
Organisme : Astellas Pharma US
ID : 163026
Organisme : AstraZeneca (GB)
ID : 158046
Organisme : Medical Research Council
ID : MC_UU_12023/20
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 3804
Pays : United Kingdom
Organisme : Janssen Pharmaceuticals
ID : 163301
Organisme : Medical Research Council
ID : 171339, 171339 and 171339
Pays : United Kingdom
Organisme : Novartis Pharmaceuticals UK Limited (GB)
ID : 158519
Organisme : Cancer Research UK
ID : A13363 and 162082
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/24
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/25
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12023/4
Pays : United Kingdom
Organisme : Efficacy and Mechanism Evaluation Programme
ID : 11/100/50
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