The effects of the pandemic have been undeniably devastating. However, this upheaval has provided the medical world with the motivation to act fast and in unison to provide better health outcomes for those affected by the virus.

The PANORAMIC trial was designed and implemented at a pace never seen before. To do this though, the right tools and support have been necessary in order to make a tangible difference.

Spiral talks to Lead Statistician Ly-Mee Yu about her involvement within the PANORAMIC trial, its aims and outcomes and why she thinks Adaptive Platform Trials like this, supported by Spiral’s agile software, are the way of the future when it comes to tackling life-threatening viruses.

Unprecedented times call for unprecedented studies

Ly-Mee Yu is the Associate Professor and Deputy Director Academic of the Primary Care Clinical Trials Unit at the Nuffield Department of Primary Care Health Sciences, Oxford University. It is here that she is also fulfilling the role of Lead Statistician of the Panoramic Trial. Ly-Mee describes trial stats as something that doesn’t excite everyone but is something she is able to find creativity in.

‘**Medical research is interesting, a lot of people may not assume this but it can be very creative in a way, different disease areas have different needs and different study designs.’**

At its core, the PANORAMIC trial aims to find effective early treatments for COVID-19. Funded by the National Institute for Health and Care Research the trial recruits people to evaluate new antiviral treatments for COVID-19 in the community, reducing the need for hospital admission, and helping them to get better sooner.

Participants are randomised to an antiviral agent or a standard of care, in their own homes. They complete a registration process online to see if they are eligible or not. If participants are eligible, they are randomised, enrolled and asked to complete an online diary for 28 days.

At present, there are over 26,000 people recruited for this trial covering 65 sites. The strategies used to recruit patients for PANORAMIC have varied. From being referred by GPs, applying through the PANORAMIC website, or by uploading a positive COVID-19 result, the recruitment process has made this trial particularly unique.

‘One of the purposes behind the trial is discovering which antivirals are effective in keeping people away from the hospitals as much as they can and alleviating the burden on the healthcare system.‘

The trial opened for enrolments with Molnupiravir as the antiviral of choice. 4 months after opening the trial the platform pivoted to add Paxlovid as a randomisation option. Later the Molnupiravir arm was closed for analysis.

Recent results published by NIHR have shown that Molnupiravir does not reduce hospitalisations or deaths among higher-risk, vaccinated adults with COVID-19. While from the outside, a drug proven to not be effective may seem a disappointing result but eliminating drugs for certain treatments allows the focus to shift to more effective treatments that have the ability to change our health systems for the better and influence government decisions globally.

The Paxlovid arm continues to recruit people. The adaptive nature of the trial means that recruitment will continue until a pre-specified probability of superiority or futility is met.

‘Research like this and its results can help and change the world and make people better, living longer’.

A platform that does it all

Spiral has been involved with Panoramic almost from its inception, providing the software required to carry out the trial remotely since October 2021. Spiral’s platform Spinnaker has streamlined the trial through a robust system that covers screening people right through to the end with results involving complex reports.

‘In clinical trials, especially academic clinical trials, we don't often have the luxury of a full system that will do everything for us, normally there would be a separate system for separate things. Spiral provides this full system’

In a world where endorsements and word-of-mouth count, Ly-Mee found herself being recommended Spiral through a collaborator. Due to the online nature of Panoramic, there was a need for a good, dependable system to work with.

‘Platform trials are still unique, not many companies can do what Spiral do or specialise in such a way - that's where we got the name Spiral from.’

Not familiar with Spiral’s platform, she describes using the new software as ‘a bit of a gamble’. However, after experiencing the breadth and combination of features that allows total control over the trial, she believes the risk has paid off. Spiral provides robust, reliable results that are making a difference in the lives of people.

‘We have found Spiral to be very hard working - one of the best things, despite the time difference, is that we have been able to call any time and Audrey and the team will pick up the phone and get on with it.’

Global community collaboration

As COVID-19 spread relentlessly across the world, it became immediately apparent the need to find effective early treatments for the virus - and fast.

The unprecedented nature of COVID meant collaboration within the medical community was vital in order to combat the virus. Panoramic was set up with extraordinary speed, recruiting a phenomenal 25,825 participants within the first 5 months.

Ly-Mee describes the collective desire to help those affected by the virus as the motivator:

‘People were willing to get involved because of the situation - They wanted to sacrifice their time and help out. At the end of the day, we want to help people get better - this is our true mindset’.

This mutual ambition to see improvements in health and increase the longevity of life for people has created a global community with a singular purpose, one that Spiral actively contributes to.

Spinnaker’s adaptability means Spiral is able to deliver software for trials such as PANORAMIC within short time frames, backed up by the experience and agility of a competent team. Being able to study multiple interventions for COVID-19 in a perpetual manner with interventions (such as antivirals) has helped clinicians, researchers, statisticians and those on the frontline deliver better health outcomes for patients.

‘It has been an interesting three years but we are constantly learning about what humans and science can do in such a short space of time. The speed of getting it done is important. We’re more prepared now for pandemics. We’ve proven that we can run trials quickly even if it takes up a lot of resources.’

The future is APT

COVID-19 saw many of us confined to our own personal bubbles. Leaving the house was often not an option, especially for those diagnosed with the virus. Traditional clinical trials typically require patients to come to an on-site facility in order to be screened, consented and possibly enrolled before partaking. A process that would prove unsuitable in a global environment with a highly contagious virus.

This has given rise to decentralised adaptive platform trials - ones that are virtual, usually conducted within the patient's own home, using software and connected devices to feed data back to sponsors and sites. For Ly-Mee and the team testing multiple different interventions, this form of clinical trial would prove most suitable for PANORAMIC, one that she believes will become standardised in the future.

‘If a clinical trial can make a patient feel unburdened in the journey they are taking while they are unwell then that is a good thing. To ensure we can collect robust data we need to make the process as easy as possible for the patients.’

As with all trials, there are challenges involved. For example ensuring patients fill out the necessary information, getting it back to the team in time, making sure the antivirals are sent to the correct patient and creating clear communication pathways for all involved. However, for all of its obstacles, Ly-Mee believes decentralisation in the form of an adaptive platform trial, especially in a climate where the pandemic has created a more socially conscious society, is the way of the future.

‘[Decentralisation] does work, we’ve demonstrated this through two trials…I think it is what other disease areas are looking into, realising it is the way to go. It’s about being provided with a robust system that works well. This is the future of clinical trials.’

Ly-Mee hopes to see the success of PANORAMIC reflected in future trials, as the use of adaptive platform trials becomes more mainstream and decentralisation more widely adopted. A return to life without Covid seems like an unlikely reality, but until that happens, trials such as PANORAMIC will continue to seek out answers to the most pressing health questions caused by the pandemic.

‘Working with different people on PANORAMIC has made the world seem smaller - in a good way. Together, we’re all about making people's lives better and improving health.’

Better Health Outcomes Together - The PANORAMIC Case Study with Lead Statistician Ly-Mee Yu