What is the MAMS design?

The Multi-Arm Multi-Stage (MAMS) trial design is a flexible and adaptive approach that has improved the speed and efficiency of clinical trials worldwide.

Unlike traditional designs, MAMS allows researchers to test multiple treatment arms at the same time, with the ability to drop treatments that don’t show promise and add new ones as they become available.  

MAMS designs provide several advantages:

  • They can test new treatments faster than traditional trials.
  • They reduce costs, as there is no need to set up a new trial for each new treatment available.
  • They facilitate recruitment as fewer number of participants are required overall.
  • They offer flexibility of dropping and adding new treatments.

Over the past two decades, we have played a pivotal role in developing and championing the MAMS design across a broad range of disease areas including cancer, infectious diseases, neurodegenerative diseases, vascular diseases, and surgery.

Our work in MAMS design has resulted in more than 84 published trials that used the MAMS-Platform design to test multiple treatments, including the RECOVERY trial in patients hospitalised for Covid-19.

The table below summarises some of our clinical trials that have implemented our MAMS design:

Trial name Disease area
STAMPEDE Prostate cancer
ICON5 Ovarian cancer
FOCUS4 Colorectal cancer
RAMPART Renal cancer
TRUNCATE-TB Tuberculosis, infection
ROSSINI2 Surgery
OCTOPUS Multiple sclerosis
WHO-RED trial  Postpartum haemorrhage


STAMPEDE: our flagship MAMS platform trial

One clear example of the impact of the MAMS design is our flagship trial in prostate cancer, STAMPEDE.

In only 20 years, STAMPEDE has:

  • Recruited almost 12,000 patients in more than 120 sites
  • Tested 10 different treatment approaches
  • 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. 

You can find out more about STAMPEDE and its impact on our STAMPEDE webpage.

MAMS software

We have developed the nstage suite of commands in Stata to help researchers calculate their sample size for MAMS trials. They include:

  • nstage calculates the sample size and operating characteristics of MAMS trials with time-to-event outcomes. 
  • nstagebinopt finds efficient MAMS designs.
  • nstagebin calculates the sample size and operating characteristics of MAMS trials with binary outcomes.

You can watch MAMS tutorial nstage videos to learn more about how to use nstage. 

MAMS design extensions

We are extending the underlying methodology of the MAMS design to increase its efficiency and broaden its application to more disease areas.

Some of our recent and ongoing work on the extension of the MAMS methodology are:

Both factorial designs and MAMS platform designs have many advantages. For example, factorial designs can make trials more efficient by independently randomising the same participants to more than one treatment, without having to significantly increase the total number of participants.

They also allow researchers to check for interactions between interventions. On the other side, MAMS platform designs improve the efficiency of the trial by allowing researchers to drop (or add) new treatments during the course of a trial.

By combining both designs, the factorial-MAMS design allows researchers to test multiple primary research hypotheses, which will lead to faster decisions about experimental treatments.

The figure shows a trial that starts as a factorial design comparing treatment A1 with A0 and treatment B1 with B0, but at a later point includes A2 as an alternative to A1 to be compared with A0.

The main advantages of the combined design include:

  • It allows the comparison of multiple treatments against the standard of care within the framework of factorial designs.
  • During the course of the trial, you can add new treatments to different randomisations in the factorial component.
  • You can introduce new randomisations 


In a MAMS design, all the experimental treatments get to the final stage if they pass the interim lack-of-benefit stopping boundaries. As a result, the number of experimental treatments in each stage is not pre-determined, so there can be large variations in the final sample size. In some MAMS designs, particularly those with a lot of different treatments, the maximum sample size might be too large either to achieve or for any funding agency to fund it.

The figure below shows seven surgical interventions (B-H) in the ROSSINI 2 MAMS selection trial that are compared against the control arm A.



In MAMS selection designs, the maximum number of experimental treatments that are taken to each stage is pre-specified, alongside a criterion for selecting them, for example, based on ranking a combination of efficacy and safety results. Traditionally, the selection of the most promising treatments has been made in phase II trials where the strict control of operating characteristics is not a particular concern. Here, our goal is to select the most promising treatments with a high probability of correct selection in the phase III setting, where we require strong control of the error rates.

The main advantage of the MAMS selection designs is that they gain efficiency over the standard MAMS design by reducing the overall sample size.

Different disease areas use different types of outcome measures. Originally, the MAMS design was developed for settings where both the intermediate and definitive outcome measures are time-to-event, as these are prominent in the initial applications in specific cancer types, such as ovarian and prostate cancer.

We are developing the MAMS design to allow for different combinations of outcome measures, the so-called generic MAMS design. The generic MAMS design allows any type of intermediate and definitive outcome. This will make use of all available data and will make the efficiency of the MAMS approach more widely available.

MAMS presentations

Recordings from the "Innovative Phase III trial designs Symposium" (June 2023) - YouTube

Sharing our expertise in MAMS platform trials

Our work in MAMS designs also extends to supporting and advising other research teams interested in using this approach in their trials. We are actively working to help others to understand and apply the MAMS design by running the MAMS clinic. In 2021, the ACORD collaboration was formed to encourage and support the development and implementation of MAMS design trials in the area of neurodegenerative diseases.

Visit the ‘Sharing Our expertise in MAMS design’ page for more resources on MAMS trials.