'Happily, we had no COVID patients today, but we are poised to continue recruitment'...The number of patients being admitted to hospital with COVID-19 may have subsided, but only time will tell what the future holds. Over recent months, the pandemic has transformed not only how we live our day-to-day lives but also how we deliver health care and research. One unexpected thing became apparent - rapid response not only saves lives but is also critical for clinical trials.
The endeavour to develop treatments, diagnostics and vaccines for COVID-19 had to be done at unprecedented speed and scale, requiring coordination across the UK's government bodies, clinical academic research experts and life science industries.
One area of focus was on the development of new treatments for COVID-19. This has centred around large, late phase trials like RECOVERY. These trials necessarily tested licensed drugs to determine if they could be used to benefit patients with COVID-19.
However, there was also a need to establish a pathway for testing new COVID-19 therapeutics, i.e. repurposing or testing unlicensed drugs. These types of studies require an understanding of the causation of disease, quick synthesis of new research findings and good knowledge of available drugs.
Usually, for such research, a small number of expert centres are involved, but it soon became obvious that speed was needed here more than ever before, in both delivery and sharing of knowledge and expertise.
This was where the NIHR's Respiratory Translational Research Collaboration (TRC) became highly valuable. The Respiratory TRC is one of five Translational Research Collaborations established by the National Institute of Health Research (NIHR) over the last ten years.
It brings together expertise, academics, clinical leaders and relevant infrastructure from different respiratory disease areas across the UK’s top universities and hospitals for experimental and early phase research. This connects our network of academics and experts, linked to their NIHR Biomedical Research Centres (BRCs), to the pharmaceutical industry to accelerate the pipeline of new molecules to medicines for patients.
Being embedded in the NIHR’s network of BRCs meant that there was already a strong foundation of translational research and scientific excellence within the Respiratory TRC. In addition, the UK experienced a fast-moving remodelling of the research and governance infrastructure during the pandemic.
This all provided a base for rapid mobilisation during the early stages of the COVID-19 pandemic and the ability to assess which early-phase drugs had potential applications in COVID-19, based on the scientific rationale.
One example of an Respiratory TRC supported study was the Phase II double blind placebo controlled clinical trial of nebulised interferon-β in hospitalised COVID-19 patients (SNG001; Synairgen), with TRC members acting as Principal Investigators (PIs), and its Operations Manager organising and coordinating NDAs, set up and site visits.
The study was one of the first Phase II COVID-19 clinical trials to commence in the UK and the first to complete, recruiting 101 patients and collecting more than 500 blood samples and swabs. The study took only 11 weeks from set up to last patient recruitment, and is due to report in July 2020.
This remarkable speed of set up and delivery can be attributed to a combination of factors. Firstly, the close working relationship between the company, Synairgen, the trial chief investigator and the TRC's members and its Operations team. The TRC provided the 'road map' for the rapidly changing landscape caused by COVID-19 and helped adapt a traditional trial design to one fit for a pandemic.
It also helped that we are made up of experienced clinical investigators and practising physicians with deep knowledge of respiratory conditions, and considerable experience in the design of studies for respiratory diseases. Lastly, we had a strong delivery arm, in part due to principal investigators who were also linked to other national delivery platforms like the NIHR’s Clinical Research Facilities and Clinical Research Network.
The Respiratory TRC was also instrumental in the development, set up, and launch of the early phase platform ACCORD, facilitating the multi-faceted discussions that were required to set up and support complex Phase II trials with exciting new compounds, never tested for viral infections. Again, with a rapidly moving pandemic and health policies, the TRC provided a pre-established network of supportive centres and expertise to help with set up and delivery.
Today, the Respiratory TRC continues to work with the national Phase II platform trials (ACCORD, CATALYST, DEFINE and TACTIC) and a further four commercial COVID-19 Phase II studies, all which are continuing to recruit. We are also working closely with other elements of the NIHR infrastructure, in particular the critical care network, which includes a phase I study in nebulised surfactant in COVID patients in Intensive Care.
The pandemic has caused us all to work in unusual ways and it has been a steep learning curve for everyone. In addition to the clear value of a pre-formed collaborative network, other notable lessons were the importance of regular and consistent communication routes between collaboration members, and cross-organisation representation to ensure effective information flow during a period of rapid changes. For the Respiratory TRC, there was also joint ownership of processes, projects, shared responsibility for delivery and simple forms of reporting. We expect to continue to lead and support COVID-19 and other commercial studies in the coming years.