Advancing Clinical Research: REMAP-CAP’s Adaptive Platform Trial Design

The clinical trials landscape is rapidly changing, with innovations like Adaptive Platform Trials making trials more flexible, efficient, and adaptive to emerging data. To support these advancements, ACTA has established the APTO SIG to promote collaboration, share knowledge, and improve the efficiency and quality of clinical trials in Australia.

Mr Cameron Green – Global Project Manager for the REMAP-CAP Trial
Cameron Green is the Global Project Manager for the Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia (REMAP-CAP) trial at Monash University. He holds a Bachelor of Science from Monash University, a Post-Graduate Diploma in Psychology from Macquarie University, and a Master of Human Cognitive Neuropsychology from the University of Edinburgh.
In 2013, he worked as a research assistant with the Delirium Research Group at the University of Edinburgh. He later transitioned to a research coordinator role in the Intensive Care Unit at Frankston Hospital, where he worked for five years before joining the REMAP-CAP trial in 2019. His research interests span critical care, epidemiology, neuropsychology, and science communication. He has a particular focus on adaptive platform trials, delirium, and the long-term outcomes of critical illness.

Background and career overview
I initially trained in neuropsychology at the University of Edinburgh, specialising in delirium in critically ill patients. This was my first experience in research in critical care, and I found it to be a really exciting, supportive, and rewarding setting in which to conduct research. After returning to Australia, I worked as a research manager of an ICU, and through that was introduced to REMAP-CAP via the ANZICS Clinical Trials Group. In 2019, I joined REMAP-CAP as Global Project Manager, shortly before the COVID-19 pandemic – a pivotal time for this trial.
Adaptive Platform Trial – REMAP-CAP
REMAP-CAP was conceptualised in 2016 after the H1N1 pandemic when researchers recognised the limitations of traditional trial designs in generating timely evidence to help guide the course of the pandemic. REMAP-CAP is a randomised, embedded, multifactorial, and adaptive platform trial designed to answer multiple questions simultaneously, ensuring rapid generation of high-quality evidence, and flexibility to address new challenges and add new questions over time. This flexibility allowed the trial to be set up in non-pandemic times to focus on critically ill patients with community acquired pneumonia and then adapt in the event of a pandemic.

Once COVID-19 appeared, REMAP-CAP rapidly scaled up from around 50 sites in 12 countries to over 350 sites in 32 countries. To date the trial has enrolled over 15,000 participants, and around half of these participants have been randomised to multiple domains, allowing for efficient use of resources by evaluating multiple questions in parallel.

• Benefits: The pandemic served as proof of concept, demonstrating that adaptive platform trials could respond quickly, assess multiple interventions, and generate high-quality evidence efficiently. Sharing our experiences can help avoid wasting resources, time, and funding. Ensuring that platform trials are well-supported and executed correctly is crucial for producing high-quality evidence and benefiting the public, participants, and funders.
• Challenges: A major challenge, especially during the pandemic, was the pressure to rapidly scale up REMAP-CAP. This trial also includes a number of novel design features, which we had to design, implement, and communicate. We learnt valuable lessons and hope to share this knowledge with others designing similar trials helping to improve efficiency and make future trials run smoother from the outset.
• Outcomes: REMAP-CAP has produced numerous primary publications since 2020, plus secondary analyses and meta-analyses results in top-tier journals.

Notably, we were among the first to show that IL-6 receptor antagonists, a type of immune modulator, reduced mortality in critically ill COVID patients. We also demonstrated that systemic corticosteroids were effective in reducing mortality, significantly influencing early treatment protocols. Additionally, we published important findings relating to anticoagulation and drugs like Simvastatin, as well as a number of findings about interventions that were ineffective, which helped clarify which treatments should be ruled out. These contributions have been crucial in guiding pandemic response globally.

Involvement with ACTA and APTO SIG
I joined ACTA in 2019 through REMAP-CAP and became part of the Adaptive Platform Trials Operations (APTO) SIG in 2022. The APTO SIG has created a valuable community for professionals working on adaptive platform trials, which are complex and often pose unique challenges. It provides a space to share insights, learn from each other, and avoid reinventing the wheel. This initiative improves the design, operation, and efficiency of trials, offering valuable resources like guidance documents and templates to streamline future trial setups. I’m excited to see the guidance documents being produced—they will be incredibly helpful for those setting up adaptive trials and will serve as a great resource when made publicly available.

ACTA’s Impact on Work and Career
I’ve been fortunate to attend the ACTA Symposium several times, and they are genuinely among the most enjoyable and valuable events I attend each year. I always learn a great deal and find them incredibly beneficial. The ACTA community has connected me with so many people, leading to useful conversations and providing valuable context when I have questions. It’s been an invaluable network to be part of.

Would you recommend that others be involved in the APTO SIG or ACTA in general?
Absolutely! I believe ACTA will only continue to grow stronger as more interested people join and contribute. There’s already such a great community, and anyone in this field who’s interested in being a part of it should definitely consider joining.