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

Publication

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

Journal Paper/Review - May 29, 2019

Schiavone Francesca, Langley Ruth, Kaplan Richard S, Parker Chris, Attard Gert, Clarke Noel W, Gillessen Sommer Silke, James Nicholas D, Maughan Tim, Sydes Matthew R, Parmar Mahesh, Hudson Fleur, Bathia Riya, Letchemanan Krishna, Masters Lindsey, Amos Claire, Bara Anna, Brown Louise, Gilson Clare, Pugh Cheryl, Atako Nafisah, past and present members of the STAMPEDE and FOCUS4 Trial Management Group

Citation

Schiavone F, Langley R, Kaplan R, Parker C, Attard G, Clarke N, Gillessen Sommer S, James N, Maughan T, Sydes M, Parmar M, Hudson F, Bathia R, Letchemanan K, Masters L, Amos C, Bara A, Brown L, Gilson C, Pugh C, Atako N, past and present members of the STAMPEDE and FOCUS4 Trial Management Group. This is a platform alteration: a trial management perspective on the operational aspects of adaptive and platform and umbrella protocols. Trials 2019; 20:264.

Type

Journal Paper/Review (English)

Journal

Trials 2019; 20

Publication Date

May 29, 2019

Issn Electronic

1745-6215

Pages

264

Brief description/objective

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.

TRIAL REGISTRATION
FOCUS4: ISRCTN Registry, ISRCTN90061546 . Registered on 16 October 2013.

STAMPEDE
ISRCTN Registry, ISRCTN78818544 . Registered on 2 February 2004.