Rapid change COVID-19 & UK clinical research

Medical tests: rapid change of clinical research

Dr Matthew Hallsworth, Head of External Relations at the National Institute for Health Research, looks how COVID-19 has brought about rapid change of clinical research; can these be embedded into future ways of working?

UK health research during the coronavirus pandemic has changed in ways which would have seemed impossible only six months ago. It is vital that we now take the opportunity to understand and embed some of our learnings from COVID-19 clinical research and make impactful changes to the landscape going forward.

Since the onset of the pandemic, the UK research community mobilised with unprecedented speed to develop multi-agency collaborative systems that enabled accelerated setup and rapid delivery of high priority research. This approach required government bodies, clinical academic research experts, regulators and the life science industry all working together in extraordinary ways.

The National Institute for Health Research (NIHR) has played a critical role in all of this. Through a collaborative process led by NIHR, COVID-19 studies assessed as having the highest potential to deliver evidence with the greatest impact within 12 months have been prioritised as urgent public health research. These studies are fast-tracked for delivery across the NHS through the NIHR, with its Clinical Research Network supporting the site set up and recruitment of patients across the country.

“If we can embed even a proportion of what has been achieved, then the UK has the potential to be the go-to country for clinical research”

Ground-breaking trials

Early in the pandemic, the NIHR and UK Research and Innovation (UKRI) established a joint funding programme for COVID-19 research, investing £24.6m in 27 priority research projects as part of two initial rounds of funding, in addition to further investment as part of a rolling funding call.

As a direct result of the NIHR’s response, a variety of ground-breaking clinical trials have been established right here in the UK, resulting in numerous global firsts and potentially life-saving breakthroughs being identified and evidenced.

Two of the six initial NIHR and UKRI funded projects have already shown their merits as world-leading and potentially game-changing research against coronavirus: the RECOVERY Trial and the Oxford COVID-19 vaccine trial.

The RECOVERY (Randomised Evaluation of COVid-19 thERapY) Phase III trial is testing a range of new and existing drugs to determine if they could be beneficial to hospitalised patients with COVID-19. With NIHR delivery support, in just three months the RECOVERY trial has been able to release results on dexamethasone, providing evidence of the first life-saving treatment for the most seriously ill patients with COVID-19. This cheap and widely available drug has been shown to reduce mortality for those severely ill with COVID-19. The preprint paper states that the drug cuts deaths in ventilated patients by one third, and deaths in other admitted patients receiving oxygen by one fifth.

One of the UK’s main strengths showcased in the RECOVERY trial, is the culture of collaboration between industry, the Government and the public sector. The trial has demonstrated the UK’s exceptional capabilities for delivering clinical trials at pace and scale across the NHS. With NIHR support, the trial was set up in record time. The first participant was recruited just 16 days after receiving the funding award, 1000 participants were recruited within the first two weeks, and around 12,000 participants have now been recruited to the study in just three months – from over 175 hospitals across the UK. RECOVERY is now the world’s largest trial of potential COVID-19 treatments.

This is in contrast to some other countries where there appears to have been less coordination of trials across research centres. Not having those collaborative structures across networks of hospitals, which thanks to the NIHR and partners have been established within the UK over the last decade, has resulted in many global clinical COVID-19 trials struggling to recruit sufficient participants and, ultimately, being underpowered as a result.

The RECOVERY trial uses an adaptive trial design. This means that it can evaluate multiple treatments at the same time, and as data is monitored continually, drugs which are not showing promising results for COVID-19 can be dropped in favour of other drugs that may have potential benefit. This ability to be able to obtain an early positive, or negative, signal of efficacy has been critical during the pandemic. The NIHR has been supporting the delivery of these types of complex trials for a number of years in the UK, and they will continue to be an increasingly important part of how we carry out clinical research.

Flagship COVID-19 vaccine trial

The UK’s unrivalled research capability, expertise and infrastructure is again highlighted by the Oxford vaccine trial of ChAdOx1 nCoV-19, funded by NIHR and UKRI as part of the first rapid response call in March 2020. This flagship vaccine trial initiated the first human trials in Europe for a potential COVID-19 vaccine. Three key members of the NIHR Oxford Biomedical Research Centre are leading the trial: Professors Sarah Gilbert and Adrian Hill of the University of Oxford’s Jenner Institute and Professor Andrew Pollard of the University’s Oxford Vaccine Group.

In a recent statement, they said: “Although it seems like a very long time since the work started, in reality it is less than four months since we first heard of an outbreak of severe pneumonia cases, and began to plan a response.”

This again highlights the unprecedented speed at which the UK coronavirus response occurred.

Fast-track approvals

Throughout the pandemic, the UK’s researchers, health authorities and regulators have also been working in extraordinary ways. The NHS Health Research Authority (HRA) implemented a fast-track approval process for COVID-19 studies, enabling their Research Ethics Committee and approval specialists to complete a full review of a study into a vaccine or immune response, or into COVID-19 prevalence or transmission, in 72 hours or less. Other UK regulators, including the Medicines and Healthcare products Regulatory Agency (MHRA), have also proved adaptable and forward thinking, quickly supporting the setup of clinical studies in a matter of weeks, rather than months, whilst still maintaining the necessary regulatory and ethical standards.

Future for clinical trials

The UK’s COVID response has collectively demonstrated our ability to accelerate study setup and delivery and has opened the potential to embed this across all future clinical trials. It will now be important to adopt some of the extraordinary ways of working from COVID-19 in a sustainable way to become part of our ‘business as usual’ approach to clinical research. If we can embed even a proportion of what has been achieved, then the UK has the potential to be the go-to country for clinical research. This not only benefits researchers and life sciences companies, but also patients in the UK, who will then be among the first in the world to benefit from cutting-edge treatments and technologies.

The NIHR will be working with partners, including the life sciences industry, to try to achieve this and ensure that when a researcher or life sciences company wants to carry out their clinical research, the UK can offer the best experience in the world.

Dr Matthew Hallsworth is Head of External Relations at the National Institute for Health Research. Go to www.nihr.ac.uk