Case study: Rapid response and coordination of early phase clinical trials during COVID-19
The NIHR R-TRC brings together ten leading centres in respiratory medicine across the UK and was ideally placed to help support rapid research into potential treatments for COVID-19.
A ready-formed collaboration able to accelerate the set-up and coordination of early-phase clinical research to tackle COVID-19
As the pandemic gathered momentum, the amount of work and communication required for successful development, set up and running of complex clinical trials with the additional policy and regulatory requirements, needed a hyper-rapid, collaborative and accommodating approach as an essential requisite for progress.
The R-TRC, a pre-existing network of respiratory clinician scientists linked through their affiliation to different Biomedical Research Centres across the UK, stepped rapidly into COVID-19 planning in February 2020.
By the time WHO declared the COVID 19 pandemic on 11 March 2020, the R-TRC had set its goals to lead, support and coordinate COVID-19 early phase therapeutic trials, focusing on drugs of high scientific rationale.
Tracy Hussell, Professor of Inflammatory Disease at the University of Manchester, and Professor Ling-Pei Ho, who specialises in respiratory immunology at the University of Oxford, were nominated as Scientific Leads to prioritise research on in-depth longitudinal immune profiling of hospitalised patients for immediate translation to drug selection, and the design of therapeutic clinical trials.
"Being a nimble and collaborative network of clinician scientists who already worked together meant that we were ready to respond and lead in an emergency" says Professor Ho.
The R-TRC worked with SMEs and pharma to identify treatments that had potential beneficial effects for patients Covid-19, for which the R-TRC could provide their clinical and scientific expertise to further develop and deliver studies.
The expertise provided by R-TRC was also able to support the UK COVID-19 Therapeutic Advisory Panel (UK C-TAP) in its role of selecting promising candidates for the various COVID-19 therapeutics research platforms.
R-TRC team of researchers discovers potential benefit of antiviral protein for COVID-19 patients
This flagship R-TRC study, led by Professor Tom Wilkinson, a consultant in Respiratory Medicine at University Hospital Southampton and supported by drug development company Synairgen PLC, showed that COVID-19 patients who received an inhaled formulation of a protein called interferon beta had a 72% lower risk of developing severe disease.
R-TRC members recruited 101 patients in 9 weeks, collected more than 500 blood samples and swabs, and took just 11 weeks from set up to last patient recruitment.
"The NIHR R-TRC was primed and ready to support the trial straight away. The expert network helped us get the project moving incredibly quickly, whilst close coordination and excellent communication helped us deliver one of the first early phase trials in COVID-19 in the world, and under the most difficult clinical circumstances. It’s a testament to the value the R-TRC brings in enabling respiratory research in the UK", Professor Wilkinson says.
Study delivers clues to severity of cases
R-TRC members also helped lead the first longitudinal immune profiling study in COVID-19 patients of varying severity and outcome revealing common features and aspects that track with severity.
The study fulfilled the R-TRC ambition of reporting within the first 6 months of the pandemic. This has had a direct impact on the selection of drugs, potential biomarkers to stratify patients for early drug trials and overall understanding of the immune response to COVID-19.
Coordinating national phase 2 platforms
Professor Ling-Pei Ho, Chair of the R-TRC, was able to play a key role in connecting and harmonising the different national phase 2 platforms.
Working together with other stakeholders, including UK Research and Innovation (UKRI), NIHR’s Biomedical Research Centres (BRCs) Clinical Research Frameworks and the UK Musculoskeletal TRC, they provided a forum for linking up four UKRI-funded national early phase 2 platforms (ACCORD, CATALYST, DEFINE and TACTIC) - providing a unified forum to discuss site initiation and recruitment, ensuring collaboration rather than competition.
"I learnt a lot rapidly by talking to a large number of people in different organisations. Our weekly meetings with the wider R-TRC members meant that the group could swiftly have these discussions and informed the next steps that could be taken", Professor Ling-Pei Ho.
This promoted optimal use of resources and maximum reach to patients during a time of dwindling patient numbers.
So far, 11 drugs have now completed phase 2 clinical trials for hospitalised patients via these platforms, and nebulised interferon is being tested in phase 3 trials globally.
Key achievements include the connection of the chief investigators to discuss interim results between the four platforms; an agreement to jointly discuss and propose lessons learnt and preparedness for a possible second wave of COVID 19; and worked with UK C-TAP which improved dialogue between RECOVERY, the world’s largest randomised controlled clinical trial for COVID-19 treatments, and the four platforms to recalibrate design as standard of care changes.
Ongoing research into recovery from COVID-19
The Post-Hospitalisation COVID-19 study (PHOSP-COVID) looks at how different patients recover from COVID-19, including factors involved in developing Long Covid, particularly in patients with the poorest outcomes.
Led by R-TRC member Professor Chris Brightling, the study connects 27 NHS and NIHR sites throughout the country, including R-TRC members as well as members of the NIHR Mental Health TRC, the NIHR Dementia TRC, the NIHR-Versus Arthritis UK Musculoskeletal TRC, the NIHR-BHF Cardiovascular Partnership, and has links to the NIHR Diet and Activity TRC.
"The achievements of the R-TRC demonstrate the importance of a well connected and skilled collaborative network during a global pandemic, and one which can rapidly understand gaps, emergent knowledge and apply this to patients' benefit", says Professor Ho.
The NIHR Respiratory TRC brings together internationally recognised investigators in the UK's leading centres of excellence to design and deliver early phase translational research at scale with industry, charities and other funders. If you’re interested in collaborating with us please contact firstname.lastname@example.org.