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Randomized Controlled Trial
. 2022 Mar 10;12(3):e055615.
doi: 10.1136/bmjopen-2021-055615.

Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials

Nurulamin M Noor  1 , Sharon B Love  2 , Talia Isaacs  3 , Richard Kaplan  2 , Mahesh K B Parmar  2 , Matthew R Sydes  2
Affiliations
Randomized Controlled Trial

Uptake of the multi-arm multi-stage (MAMS) adaptive platform approach: a trial-registry review of late-phase randomised clinical trials

Nurulamin M Noor et al. BMJ Open. .

Abstract

Background: For medical conditions with numerous interventions worthy of investigation, there are many advantages of a multi-arm multi-stage (MAMS) platform trial approach. However, there is currently limited knowledge on uptake of the MAMS design, especially in the late-phase setting. We sought to examine uptake and characteristics of late-phase MAMS platform trials, to enable better planning for teams considering future use of this approach.

Design: We examined uptake of registered, late-phase MAMS platforms in the EU clinical trials register, Australian New Zealand Clinical Trials Registry, International Standard Randomised Controlled Trial Number registry, Pan African Clinical Trials Registry, WHO International Clinical Trial Registry Platform and databases: PubMed, Medline, Cochrane Library, Global Health Library and EMBASE. Searching was performed and review data frozen on 1 April 2021. MAMS platforms were defined as requiring two or more comparison arms, with two or more trial stages, with an interim analysis allowing for stopping of recruitment to arms and typically the ability to add new intervention arms.

Results: 62 late-phase clinical trials using an MAMS approach were included. Overall, the number of late-phase trials using the MAMS design has been increasing since 2001 and been accelerated by COVID-19. The majority of current MAMS platforms were either targeting infectious diseases (52%) or cancers (29%) and all identified trials were for treatment interventions. 89% (55/62) of MAMS platforms were evaluating medications, with 45% (28/62) of the MAMS platforms having at least one or more repurposed medication as a comparison arm.

Conclusions: Historically, late-phase trials have adhered to long-established standard (two-arm) designs. However, the number of late-phase MAMS platform trials is increasing, across a range of different disease areas. This study highlights the potential scope of MAMS platform trials and may assist research teams considering use of this approach in the late-phase randomised clinical trial setting.

Prospero registration number: CRD42019153910.

Keywords: clinical pharmacology; clinical trials; infectious diseases; oncology; public health.

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Conflict of interest statement

Competing interests: MRS reports grants and non-financial support from Astellas, grants from Clovis, grants and non-financial support from Janssen, grants and non-financial support from Novartis, grants and non-financial support from Pfizer, grants and non-financial support from Sanofi, during the conduct of the study; personal fees from Lilly Oncology, personal fees from Janssen, all outside of the submitted work.

Figures

Figure 1
Figure 1
Search strategy and inclusion of late-phasemulti-arm multi-stage (MAMS) platform trials. This flow diagram represents the search criteria and results for late-phase MAMS platform trials identified and eligible for inclusion in this review. The date of lock for new trial registrations was 1 April 2021.
Figure 2
Figure 2
Increasing uptake of late-phase trials using the multi-arm multi-stage (MAMS) platform approach over time. Hosepipe plot demonstrating increasing uptake of MAMS platform for late-phase clinical trials over time, accelerated by uptake during the COVID-19 pandemic. The date of lock for new trial registrations was 1 April 2021.
Figure 3
Figure 3
Countries involved in late-phase APTs using the MAMS protocol approach. (A) country where organisations based around the world which were leading late-phase MAMS platform trials in the pre-COVID-19 era and since the COVID-19 pandemic. (B) countries around the world recruiting to late-phase MAMS platform trials in the pre-COVID-19 era and since the COVID-19 pandemic. APT, adaptive platform trial; MAMS, multi-arm multi-stage.
See this image and copyright information in PMC

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