Published: 17 May 2022
Professor Andrew Ustianowski, Joint National Specialty Lead for Infection, and Tracy Harman, Head of Medical Directorate at the NIHR Clinical Research Network, reflect on how COVID-19 impacted the research delivery landscape and how the research community can learn from this legacy.
COVID-19 has had a seismic impact on research delivery. From the speed at which studies were identified, launched and had their results put into practice, to the methods of streamlining and optimising key processes, the UK successfully adjusted to prioritise and deliver an extensive list of clinical studies to help in the early fight against coronavirus.
The Ask
In January 2020, when the first COVID-19 patients were identified in the UK, we enacted our standard Urgent Public Health (UPH) processes to collect as much information on the patients as early as possible. This resulted in the set-up of the ISARIC Clinical Characterisation protocol, which has since recruited over 290,000 individuals.
Unfortunately, the scale and speed of the pandemic quickly overwhelmed existing processes and was causing major problems within the NHS for clinical care.
As a result, in March 2020 the government asked the Clinical Research Network (CRN) to develop a national review and prioritisation system for COVID-19 studies across the UK. Any study wishing to access CRN or NHS resources during the emergency phases of the pandemic underwent expert review. These studies needed to fall within one of the categories of: Therapeutics, Vaccines, Diagnostics or Collection of samples and data. Prophylactics and Mental Health, where there was a life-threatening risk, were later added.
With so many vitally important and large scale clinical studies to set up across a huge geographical and demographic spread, the challenge was immense. It was also key that disruption to other research portfolios and the NHS was kept to a minimum — a difficult task with many research colleagues deployed to frontline healthcare roles early in the pandemic.
When it came to the pre-existing research system for vaccines, this was largely hospital- and healthcare-site based, and mainly paediatric focused, with a small number of specialist centres.
Previously, the NIHR had not done anything of significance to this scale and pace in the area of infectious diseases or vaccinations.
The Approach
The UPH study review process consisted of four steps. Firstly, we asked study leads to apply for UPH status, providing the protocol and details of any study supplies needed. The studies were then reviewed by a multidisciplinary group set up by the CRN, chaired by Medical Director Prof Nick Lemoine.
The group included the Devolved Administrations, public representatives and expert members of the research and clinical communities. The final decision as to UPH badging rested with the Chief Medical Officer, Professor Sir Chris Whitty, based on group recommendations.
Once designated as UPH, regulatory approval was expedited and access to CRN support prioritised. At this stage we assisted in identifying sites for delivery and facilitated the set-up processes. The final stage centred around the actual coordination of the study, including how it was managed and monitored.
The CRN received a staggering 1,600 applications in total, with 101 studies UPH approved. As a result, these studies have recruited over 1.3 million participants from across 8,773 sites. This would have been impossible without the organisation's flexibility and determination to support pivotal studies across the UK.
The Results
There are many examples of just how important this study set up approach has been and how the studies launched have (and will continue to) give us strong tools in the fight against COVID-19.
Within a week of being UPH-designated, the RECOVERY trial (a platform study set up in March 2020) recruited its first participant and within that first week of opening it was set up and recruiting at 50 hospital Trusts. The study continues to recruit at 178 Trusts in the UK, producing game-changing results for a number of therapeutics, including dexamethasone.
In November of 2020, within just eight weeks the Novavax COVID-19 vaccine study recruited over 15,000 participants at over 30 UK sites. The study remains the largest ever double blind, placebo-controlled vaccine trial to be undertaken in the UK.
Additionally, there have been global first participant recruits in four multinational vaccine studies. The data on vaccines gathered in the UK, on aspects such as intervals between dosing, boosters and how they perform within different population groups, have informed many countries’ vaccination programmes. Something which the NIHR and all research staff across the UK can take great pride in.
In total the NIHR CRN has supported 364 studies (UPH and non-UPH badged), recruiting more than 2.7 million noble participants. These results would not have been possible without this coordinated, prioritised national response, the product of effective research collaboration between Trusts and primary care sites across the UK, the Health Research Authority (HRA), Medicines and Healthcare products Regulatory Agency (MHRA), and the Vaccines Taskforce.
The prioritised funding, review and delivery of the UPH studies has allowed the UK to rapidly answer questions of national and indeed global importance.
In order for this study delivery approach to leave a lasting legacy, its key learnings need to be translated to non-COVID-19 studies. By drawing upon the invaluable experience of running adaptive, nationally prioritised trials, the use of platform studies, expedited processes and approvals, we can be ready to tackle new challenges.
Partnerships with regulators, Department of Health and Social Care Taskforces, Devolved Administrations, Clinical Trials Units, the R&D community and funders that were so vital through COVID have proven to be sustainable post-COVID, enabling us to think bigger in how we approach research delivery challenges in the future.
Bringing the voice of the clinicians, researchers and patients into delivery processes has proved invaluable and will be a further legacy of the COVID era.
A timeline of the NIHR’s response to the pandemic demonstrates the pace and scale of the work carried out.
This piece follows Prof Ustianowski and Tracy Harman recently presenting the NIHR’s Clinical Research Network (CRN) experience and learnings at the European Society of Clinical Microbiology and Infectious Diseases Conference in Lisbon.