Lauren Barina is a Global Clinical Trial Manager of the Staphylococcus aureus Network Adaptive Platform (SNAP) Trial, which is a large, international, multi-centre Adaptive Platform Trial which aims to improve treatment outcomes for patients with Staphylococcus aureus bloodstream infections.
Lauren has a background in neuroscience, bioethics, research ethics, and research governance and is passionate about supporting researchers to make ethically informed and participant-focused decisions in the ongoing conduct of research studies.
Please provide a short background on your current role and career to date
I am currently one of two Global trial Managers for the SNAP trial. I have worked at the Doherty institute in Adaptive Platform Trials (APTs) for 4 years, and prior to that, I worked at St Vincent’s Hospital as an ethics submissions specialist and also in their Research
and Governance office doing a variety of things such as ethics review, governance review, quality assurance, etc.
Please tell us about the Adaptive Platform trial you are involved with – Staphylococcus aureus Network Adaptive Platform (SNAP)
Trial
How long has this trial been running?
It’s been running since 2020, but it’s been recruiting since 2022, so running for about 5 years, recruiting for about 3 years.
Why was this trial developed?
This trial aims to improve outcomes for patients with staph aureus bloodstream infections. Optimal management of these infections is uncertain and there are few published studies that compare available treatments that are already used in hospitals. Current evidence is based on less than 3,000 patients enrolled in randomised controlled trials. So, it was felt that there was an unmet need for a large RCT.
How many participants and active sites does this trial have?
There are 4,200 participants in the SNAP platform, which is the randomised aspect that is nested within a clinical quality registry; and there is an additional 4,500 participants just in that data collection clinical quality registry. The trial is currently active in 9 countries and
131 hospitals, but we continue to open and grow into more countries.
Why was this trial design selected?
The chief investigators had finished and published the CAMERA-2 trial, in which they randomised 350 participants with MRSA bacteraemia, and at the same time were in discussions about Adaptive Platform Trials. So, at this point a larger trial and an adaptive approach was on the forefront of their minds. The attraction of the adaptive structure was that it provided the ability to answer multiple
research questions simultaneously within the trial infrastructure and add/drop/change interventions when statistical triggers were reached.
What are the benefits to using this trial design?
Benefits include:
* The ability to answer priority research questions in an efficient manner.
* Be able to drop or change interventions when statistical triggers are met and therefore, be able to answers questions more quickly.
*Be able to borrow data across different populations.
What have been the main challenges with this trial design?
Coming from my perspective as a manager, operational challenges we have faced include:
* Data management burden – challenge to keep up with data demands; including frequent analyses associated with statistical design; maintaining a regularly cleaned dataset as the trial aims to run for many years it is important to keep this as an ongoing process; keeping data from multiple regions harmonised; collating data from various regions in line with their regulatory requirements.
* Ethics and regulatory approvals – trial design doesn’t fit the mould for most ethics and regulatory document templates. So, trying to explain what you are doing using a form that is not fit for purpose can be difficult.
* Communication of Results – Our trial uses Bayesian statistics that is not well understood by people who are not statisticians, including clinicians or lay people. We need to really work hard to clearly explain results and disseminate that information to the wider community in a format that people can then interpret.
* Collaboration Complexity – can be difficult because there are so many people involved;
in our working groups alone, we have over 230 people, and then another few hundred investigators. We must think about how we
can efficiently continue to work together to generate and act upon important ideas, operationalise them, and do this via the correct governance process.
What significant outcomes have come from using this trial design?
We think that even being able to recruit over 4,000 participants into this trial when only 3,000 people had ever been previously randomised to a study about staph aureus bacteraemia is a significant outcome for the study. Not only is it 4,000 patients, but because each patient is randomised to more than one intervention (on average about x1.5), it is over 6,000 randomisations. Another outcome that has been quite exciting is that this trial design forced us to think of an innovative way to consent people by providing them with information that they need to make a decision and explain to them a really complicated trial design. By having a simplified consent model that SNAP uses has been a great outcome. We are also working on incorporating smaller sub studies, nested randomised controlled trials, or sample collection studies that can use the existing infrastructure to answer a smaller research question.
Adaptive Platform Trial Operations Special Interest Group (APTO SIG)
How long have you been involved in ACTA and the APTO SIG?
I had heard about ACTA for a long time from my previous work at St Vincent’s Hospital and attended a few conferences over the years. I became more involved with ACTA when I joined the APTO SIG, which I have been involved in since its inception 3 years ago.
How did you hear about the APTO SIG and why were you interested in joining?
I heard about it from my manager, who was then co-chair and assisted in the establishment of the working group. I don’t usually interact with a lot of clinical trial project managers and people doing the same kind of research, especially in adaptive platform trials. So, it has been interesting to liaise and share knowledge with others who are more or less experienced than you in a way that we wouldn’t otherwise get an opportunity to do.
What has been the most valuable outcome from being involved in the APTO SIG?
Meeting other people working in APTs. Also, the Operational document will be a huge benefit to a lot of people, and I am excited for that to be released and shared.
Does the APTO SIG have value for the broader research community and clinical trial sector?
I think so. Many challenges are not unique to APT, but they can be confounded or exacerbated by the complexity of APT’s. Having a space to discuss ethics, regulatory contracts, and other topics we discuss in the SIG helps us to find the best way to do certain things and also challenging the templates that are available to improve the process for everyone. Therefore, I could see how this is beneficial to other people in the clinical trial sector.
Has being part of ACTA influenced or benefited your work, career, or professional confidence?
Yes – it has been great to meet other people, expand the network I can communicate with, and I have learnt a lot from others that I can apply to my own work. Also to know that your knowledge is beneficial to others who are in initial stages in their trial development has been nice to grow my professional confidence.
Would you recommend that others be involved in the APTO SIG or ACTA in general?
Yes absolutely. It’s not a burden and I look forward to the meetings and outputs.
Is there any other way that ACTA could support Adaptive Platform Trials?
It would be useful to progress a community of practice, being able to share from others in project management roles, but also invite key people from legal teams, ethics officers, stakeholders, regulatory people, etc. It would be worthwhile to have an open discussion so that they can explain to us their challenges with reviewing APT’s, and we can explain to them our challenges undertaking their processes. I think that would be a terrific way to start those conversations and get more people on the same page.
Would you maintain involvement with ACTA in the future (e.g. use ACTA resources and attend/present at ACTA events)?
Yes.
Resource Documents
Innovative Trial Design and the Pdaptive Platform Trial Operations Special Interest Group (APTO SIG)
