Early Psychosis Multi-arm, Multi-stage Platform Trial (PUMA)

We invite you to join our PUMA team!

PUMA is currently looking for collaborators to be part of our work. We are looking for both lived experience experts and clinicians.

Read more about our existing team and wonderful collaborators here.

What are MAMS platforms

PUMA trial, funded by Wellcome, is a 30 month design and set up phase of the first adaptive Multi-arm, Multi-stage (MAMS) platform for clinical trials for early psychosis.

This novel way to design clinical trials allows for:

• Testing multiple treatments simultaneously: This speeds up the process and identifies ineffective options faster.
• Prioritizing interventions: The platform starts with repurposed drugs and new compounds with strong potential. These will be evaluated against a standard of care in an established and curated trial platform (for this project: based in English early intervention in psychosis (EIP) services)
• Adapting based on results: intervention arms that are going to fail i.e. trials that aren't working are stopped, freeing resources for further prioritised options.

This 10-minute video, offers a comprehensive explanation of MAMS trial platforms. The MAMS approach for clinical trials draws inspiration from the success of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial revolutionizing prostate cancer treatment evaluation.

Why is PUMA Important?

Psychotic disorders are recognized as a global health burden but there has been no significant therapeutic advance for half a century. Some people with early psychotic disorders recover completely, but the outcomes for too many are bleak. PUMA hopes to improve patient outcomes in early psychosis by dramatically accelerating the delivery of clinical trials and transforming treatments in this area. To achieve this, we will establish a MAMS trial platform that will be truly co-created by the whole early psychosis community in the UK – patients, carers, clinicians, academics and regulators. Our aim is for PUMA to become the leading national platform for the delivery of clinical trials in early psychosis.

• Concurrent evaluation: testing multiple potential treatments simultaneously not only streamlines the process but also enables early termination of ineffective arms, maximizing efficiency.
• Stakeholder co-creation: Patients, carers, clinicians, academics, and regulators are all integral parts of PUMA. Their combined expertise ensures the trials are relevant, inclusive, and address the most pressing needs in early psychosis research.
• Improved trial design: By incorporating patient and carer perspectives, PUMA trials will directly target what matters most to those living with the condition.
• Faster results: By utilising the MAMS platform PUMA has the potential to significantly accelerate the development of new and effective treatments for early psychosis.
• Increased access to research: By making trials more inclusive and efficient, PUMA aims to offer more people with early psychosis the opportunity to participate in research.

What do we hope to achieve?

PUMA's vision is to become the leading national platform for early psychosis clinical trials, paving the way for a future with better treatment options. Beginning with early psychosis, we hope the design might become more widely used in the mental health field, putting it on a par in terms of evidence from RCTs with conditions such as prostate cancer (where the STAMPEDE trial has completely changed the standard of care several times and improved life expectancy), Covid-19 where the UK Recovery trial platform led the world’s response, and several neurological disorders where the recent UK pioneers are supporting our efforts. PUMA will complement investments in discovery science supported by the Mental Health Mission and UKRI mental health platform hubs by rapidly evaluating their therapeutic outputs in real-world settings.

How PUMA works?

PUMA focuses on developing the core MAMS protocol and the necessary infrastructure ready to be implemented. Working groups (see governance structure) will be established, involving patients, carers and clinicians across the country. We will select a hub and chief investigator for the platform and establish a national network of research sites. Our aim is to establish an infrastructure to enable the rapid trialling of new treatments in early psychosis. Preparatory work will also include: 1. systematic review, a comprehensive analysis of existing early psychosis drug trials to inform future trial design, outcome measures, and treatment selection. 2. Delphi Process, a structured survey-based approach to gather stakeholder perspectives and potentially reach consensus on critical aspects of MAMS trials.

The project aims will be achieved through five working groups (WG) (Trial Design WG, Treatment Recommendation WG, Outcome Measures WG, Patient and Carers Engagement WG, and Infrastructure WG) discussing such questions.  Each working group will have patient and carer representatives within their membership. There will also be a separate working group only consisting of patients and carers and MQ representatives to reflect on activities across the whole project. The organogram of our structures, and leadership is detailed here. 

 Each working group has specific aims:

Trial Design working group: To develop a Master Protocol that will describe the objective(s), design, methodology, statistical considerations, and organisation of a MAMS trial, and ensure the safety of the trial participants and integrity of the data collected.

Treatment Recommendation working group:  To develop a priority list of drugs for inclusion in the trial and to prioritise and select 'high potential' drug candidates that will allow seamless addition of investigational arms in the future to the MAMS trial.

Outcome Measure Selection working group:  To select the most appropriate intermediate and final phase outcomes to be used, which are clinically relevant, meaningful to patients and align with regulatory requirements.

Infrastructure working group: To develop a model for the infrastructure to support successful MAMS trial delivery.

Patient and Carer Engagement Working Group: To ensure effective and meaningful lived experience (patient and carer) contribution to all aspects of the design of PUMA, alongside increasing awareness to support and facilitate recruitment and retention.

Lived experience involvement

PUMA prioritizes patient and carer involvement throughout the process and so is partnered with MQ Mental Health charity. All the working groups will have lived experience experts (LEE), as members and/or co-chairs, ensuring their perspectives are reflected in all aspects of the research. A separate working group solely consisting of patients, carers and MQ representatives, will also be established, to reflect on activities across the whole project.  LEE will play a key role in shaping the PUMA trial by providing insights on:

• Who can participate (eligibility criteria)
• Trial duration
• How to measure success (outcome measures)
• Making the trial process easier and more welcoming
• Reaching underserved communities
• Including non-English speakers