Covid-19 is changing the landscape of UK clinical research, but will these reforms last beyond the pandemic?

The holy grail of research and development in life sciences is integrating life changing treatments into clinical use at pace. However, this must be done following robust assessment and regulation. In this context, governments across the world are showing flexibility in adapting research cycles to accelerate the implementation of new treatments in response to the Covid-19 pandemic.

In the UK this is no different, with a growing part of the Covid-19 strategy now based around streamlining research cycles and getting treatments and therapies to the people that need them – the patients. In getting to this objective, we must learn new practices, ensuring that, while the assessment and regulation of new compounds will benefit patients in the short term, the UK’s competitive position in the global market is secured beyond the pandemic.

This was the topic of discussion at a recent Public Policy Projects (PPP) Virtual Healthcare Breakfast with Dr Jonathan Sheffield, former Chief Executive of the National Institute for Health Research (NIHR), and James Brook, Head of UK and Ireland Clinical Delivery at IQVIA. Both Jonathan and James sought to outline the seismic shift we are currently experiencing in UK clinical research.

Covid disruption to clinical trial process

It goes without saying that the pandemic has caused major disruption to clinical trials across the UK. “No pharma company has been able to shield from the effects of the pandemic,” said James. “All the top 20 pharma companies are delaying both the start of new trials and interrupting or delaying ongoing trials.” Similarly, the NIHR have had to pause much of its work to focus on the pandemic.

There has been an apparent shift from research back to clinical care in order to deal with the immediate crisis. With research staff being transferred away from trial sites, Jonathan estimates that the UK is about 1000 clinical research nurses down from this point last year. While hospitals focus on Covid-19 clinical care, patients have not been able to attend research related appointments to anywhere near previous levels. Jonathan estimates that some 45 per cent of all routine research in England were paused at some point.

A UK-wide, system level response

To progress potentially effective treatments, the UK has had to rapidly adapt to a new normal. A national strategy, currently being spearheaded by Professor Chris Whitty, is ensuring that Covid-19 urgent public health research (UPHR) is now being prioritised to gather necessary clinical and epidemiological evidence. This is informing national policy to enable new diagnostic testing, treatments and vaccines to be developed. Government financial support has also become available to assist with prioritising these treatments, helping to coordinate and deliver studies at pace, regardless of sources of funding.

As a result, a collective, system-wide approach to clinical research has emerged in the UK that is expediting research across the country. This is a collaboration involving the NIHR, Public Health England, UK Research and Innovation, HRA, MHRA and other relevant bodies. Process time frames between different organisations are now being brought together to further streamline this pipeline of innovation. “We now have a complete picture of all Covid-19 UPHR activity across the UK,” noted Jonathan.

“What we have demonstrated is a highly adaptable research health system that has led the world over the last few weeks,” he continued. “This is a UK system-wide approach to prioritising research that has enabled the swift prioritisation of treatments effective against Covid-19.

“We have had to completely change the way in which we deliver and monitor usual research while the focus is put on this urgent public health crisis,” added Jonathan, who hailed the use of remote and digital clinical trials as a key enabler for research cycles.

The results speak for themselves. Almost 80,000 people have been recruited into 43 different Covid-19 clinical studies since the start of May – ranging from observational studies to major phase three trials.

One such trial is RECOVERY, or the Randomised Evaluation of Covid-19 Therapy. The study was granted a UPHR badge on 11 March and, just seven days later, the first patient joined the study. As of two weeks ago, a further 8,000 patients have been recruited. This represents one of the largest Phase Three Covid-19 clinical studies anywhere in the world. The trial for Remdesivir, developed by Gilead, was granted a UPHR badge on March 18 and recruited its first patients by the March 30, accomplishing its initial UK recruitment target in just 16 days with recruitment growing further still. The study has a global target of 2400 subjects and already has 17 active sites for testing.

“Organisations are now working in a systemic, parallel approach,” said Divya Chadha Manek, Head of Business Development for the NIHR “we are now working together at pace and scale – expediting these innovations has been a huge success.” Divya was speaking at a recent IQVIA webinar hosted by pharmaphorum. The added good news, she said, is that these trials are occurring while the NIHR is also able to begin restarting its wider clinical research portfolio – previously paused to focus resources on Covid-19.

ACCORD

Not resting on the success seen so far, Jonathan said, “we identified the need for another, earlier phase research platform that will enable the rapid licencing and even earlier implementation of treatments.”

This was the genesis for the ACCORD initiative, or the Accelerating Covid-19 Research and Development platform. It is a new programme, announced by the Department of Health and Social Care at the end of April, designed to streamline the clinical research process and provide earlier indications of whether drugs can be used to improve outcomes for vulnerable patients with Covid-19.

Comprehending the need for ACCORD and other such platforms requires an examination of the current UK position within the global research market. “Covid-19 is not just a UK problem, nor is clinical research just a UK phenomenon,” said James, who was eager to highlight that UK clinical research trials have long needed streamlining. Globally, he said, the UK accounts for around 3-4 per cent of commercial activity in clinical trials. Given the prestige with which UK clinical research is regarded around the world, it is baffling to many as to why the country is currently leaving such a small commercial footprint in this space. The reason for this, put simply, is the UK’s sluggishness in turning treatment into delivery.

UK site clinical selection to site activation is on average 42 per cent slower than in the USA. Ethics approval process is currently five times slower than the USA and twice as slow than in the Ukraine and Poland. Meanwhile, the Eastern Europe market continues to grow due to their highly engaged approach to clinical research.

IQVIA, for its part, has made a series of recommendations to the UK Government, seeking to drive changes to UK research mentality and ensure that more patients get access to life changing conditions. These recommendations include the establishment of a single national commercial UK ethics committee to accelerate clinical trial approval and for nationally funded molecular pathology testing to enable precision trial enrolment. IQVIA are providing the single UK trials platform for ACCORD, a unique collaboration to fast track and repurpose drugs into phase two studies.

Both James and Jonathan stressed that the success is of this initiative is rooted in collaboration. “This is working through an incredible sense of partnership,” said James. “We are all working hand in glove to accelerate trial start up and enhance delivery to simplify research.”

ACCORD is hyper accelerated UK clinical research, compounds are selected by a government committee and then assessed by IQVIA on their suitability for phase two availability. That compound is then repurposed against a sub protocol which is developed in 72-hours.

The significance of this pace cannot be understated. The 72-hour period includes data management, statistics, drug supply, randomisation and the deployment of staff trained to support the trial site. Following this, the sub protocol is then submitted to the MHRA and NIHR for approval within a 48-hour time period. “To be clear,” said James, “the standards of these studies have not changed, but what we are seeing is an 18-month time cycle being compressed into a matter of weeks.” So far, four different compounds have already entered clinical trials in four different UK sites.

We must not waste progress

Could the adversity posed by Covid-19 ignite a long-term UK research transformation? “The seismic shift of this pandemic can certainly have long term effects on the practice and implementation of UK research,” noted Jonathan, “but we must ensure, through the incredible work being conducted across the country, that we learn lessons to inform our research policy beyond the pandemic. We have a unique opportunity within the NHS to really lead the world in clinical research.”

Clearly, the UK is unique in the way in which it conducts research. This has helped drive its response to Covid-19 so far. However, there is a significant appetite for reform, as Angela McFarlane, Market Development Director at IQVIA recently noted, “if the Government does not rapidly embed learnings achieved during these challenging times– then we will miss the opportunity to take advantage to become the world’s leading country for clinical research.” In Angela’s mind, the UK must now be focused on making this country a standard bearer for precision clinical research.

Throughout this pandemic, the UK has demonstrated the speed at which it can complete clinical research trials when the pressure is on. As James concluded: “The collaboration we are seeing is unprecedented and demonstrates how the UK can lead the world in delivering innovative research at pace – saving countless lives in the process.”