'25 at 25': The Multi-Arm Multi-Stage (MAMS) design

04 Jan 2024

As we celebrate the 25th anniversary of the MRC Clinical Trials Unit at UCL (MRC CTU at UCL), we take pride in reflecting on our pioneering work on the multi-arm multi-stage (MAMS) trial design, which has improved the speed and efficiency of clinical trials worldwide. This article is the first in a series highlighting 25 major achievements from the 25 years since the MRC CTU at UCL was formed.

The MAMS design, a flexible and adaptive approach, has helped bring life-changing treatments to patients faster than ever before. Unlike traditional designs, MAMS allows researchers to test multiple treatments at the same time, with the ability to drop treatments that don’t show promise and, as a platform, allow the assessment of new candidate treatments as they become available.

Over the past two decades, the MRC CTU at UCL has played a pivotal role in developing and championing the MAMS design. Our dedicated trial teams have worked to implement this design across a broad range of trials. One clear example of the impact of the MAMS design is our flagship trial in prostate cancer, STAMPEDE. In only 20 years, STAMPEDE has tested 10 different treatment approaches and these have led to improvements in the standard of care for prostate cancer four times. This progress would have taken many decades using traditional trial designs. Thanks to the advances driven by STAMPEDE and other research, men diagnosed with prostate cancer now live up to four years longer on average than when the trial started in 2005.

By identifying promising treatments faster, we prioritise the well-being of participants and accelerate access to potential new treatments.

Our work in MAMS designs also extends to supporting and advising other research teams interested in using this approach in their trials. Sharing our expertise in optimising the design, implementation and analysis of MAMS trials is very important to us, as it ensures that the benefits of these novel designs are applied to a diverse range of disease areas.

Many trials in other disease areas now use the MAMS design. Our Octopus trial is the first MAMS trial in multiple sclerosis, aiming to find new treatments more quickly for progressive multiple sclerosis. MAMS designs were also widely used for COVID-19 trials, which were able to test many potential treatments in a short amount of time during a global public health emergency.

Since the MAMS design was first conceived, our methodologists have expanded it to work in different situations. The MAMS-ROCI design is a new variation of MAMS that compares different treatment durations, doses or frequencies to identify the optimal ones.

Image: diagram explaining how the MAMS design works and the advantages of this approach (faster, cost, facilitates recruitment and flexibility)

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