The academic response to COVID-19

Tony Rostron

For those of us who contribute to patient facing research, there were signals in early March that our working lives were about to change. The safety implications related to recruitment of and sampling from patients in studies who were potentially infected with SARS-CoV-2 needed to be considered. As a result many NIHR portfolio studies, supported by their funders, decided to pause recruitment.

While trusts began enacting their plans to meet the surge, universities also changed. Medical students in the early years were being sent home and those in their final year prepared to start their medical careers early. Some research groups in Newcastle and elsewhere redirected their work towards studying COVID-19, and others gave up their time and equipment to help with the national demand for diagnostic testing. Where possible, people began working from home.

As clinical academics combine their clinical duties with research and teaching responsibilities, universities and large funding bodies (such as the NIHR, the Wellcome Trust and the MRC) supported the redeployment of clinical staff to full time clinical work, particularly those of us in acute specialties. This was a departure from my normal working pattern, but through an informal network in critical care research I received a message of support from Charlotte Summers and many more have circulated. Some research nurses were also redeployed to clinical duties, but with CRN and local R&D support, here in Sunderland we have managed to increase our recruitment to studies from five to seven days a week.

The research response to COVID-19 that has been made by the NHS, and in particular the UK critical care community (led by the NIHR critical care specialty group chaired by Paul Dark) has been world leading.

It was recognised early that research efforts needed to be focused on the management of COVID-19. Platform studies were developed for primary care, secondary care and critical care, and approved by the Chief Medical Officer as being Urgent Public Health (UPH) research studies. This enabled them to be prioritised for set-up by local R&D, access support from the clinical research networks (CRN) and give them preferential access to potential treatments.

The studies which occupy the critical care platform are both observational to help identify treatments, and interventional to test potential treatments in a controlled fashion. This approach ensures that we identify potential treatments as quickly as possible and determine if they are effective in treating patients or whether they result in harm. Outside of controlled studies, these signals would be lost.

In the absence of evidence, clinicians develop their practice based on experience. Resulting beliefs can be hard to challenge and study participation is sometimes declined citing a lack of equipoise. It’s important to remember however that existing mental models may be incorrect, and that challenging your belief system is to be encouraged in a world of uncertainty.

The largest observational study in critical care is Genetics Of Mortality In Critical Care (GenOMICC) led by Kenny Baillie from Edinburgh, whilst the largest interventional study is the Randomized, Embedded, Multifactorial Adaptive Platform Trial for Community- Acquired Pneumonia (REMAP-CAP), conceived by a truly international consortium of the most prominent critical care trialists and overseen in the UK by Tony Gordon from Imperial College and Kathy Rowan from ICNARC. These trials demonstrate both the preparedness and responsiveness in critical care research, by deploying pandemic protocols that recruit patients from countries around the globe. Kenny has made it his ambition to recruit every patient who receives invasive mechanical ventilation for COVID19, but he can only do this with comprehensive participation.

REMAP-CAP also has a particularly innovative design. Both singular and combination treatments are being evaluated. The initial domains of treatment in the pandemic protocol are antivirals, steroids, immune modulation and macrolides, but as evidence emerges other domains can be added. Whilst the trial is ongoing, so too is analysis which means that effective treatments can be identified earlier, and the adaptive nature of randomisation means more patients will receive effective treatments. This means that patients who participate in REMAP-CAP are more likely to benefit than those that don’t.

In addition to the large platform studies, other trials have received UPH approval. Some of these have been repurposed, such as the REALIST study led by Danny McAuley. REALIST aims to determine the role of mesenchymal stem cells in the management of COVID19 instead of ARDS of other aetiologies.

Other trials have been commissioned by the NHS to address an important question, such as RECOVERY RS led by Gavin Perkins and Danny McAuley. RECOVERY RS (not to be confused with the similarly named RECOVERY trial of therapies for COVID-19 in hospitalised patients) aims to determine the most effective way of delivering respiratory support to patients with COVID19, and may also facilitate further collaborative working between respiratory medicine and critical care.

Undoubtedly more studies will come soon, and the engine room of critical care research is definitely humming.  For those units who are less familiar with research, I would encourage you to take the plunge, I’m sure you’ll find it challenging but fulfilling and support from the local clinical research networks will be forthcoming.

Research in critical care is not a luxury for our patients, it is a necessity and COVID19 may become a really positive agent for change and allow us to embed research into normal everyday practice.

Since the start of the pandemic, the approach to critical care research may have become more Spartan than Athenian, but the spirit of collaboration has definitely been preserved.

Tony Rostron is an academic critical care consultant at Newcastle University and South Tyneside and Sunderland NHS Foundation Trust.