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Duncan Richards, Climax Professor of Clinical Therapeutics and Director of the Oxford Clinical Trials Research Unit (OCTRU) is interviewed about clinical trials and the challenges of running them in a pandemic.

The COVID Clinical Trial Planning Group has been really focused on a strategy for our clinical studies, says Duncan

What has been your role in the Oxford response to the COVID-19 pandemic?

This pandemic is characterised for me by two groups. There are those who are on the front line, treating patients, often rushed off their feet dealing with immediate needs of patients and logistic matters.

In a place like Oxford you also have a huge number of 'armchair generals' who are isolated at home and really want to make a contribution. They have the opportunity to devour the emerging literature and to formulate great ideas. We need both these groups to work together to deliver for patients.

I am leading the COVID Clinical Trial Planning Group, which works at this interface. We have a real multidisciplinary group encompassing immunologists, respiratory, infectious disease, intensive care, emergency medicine and gerontology. The national framework sets the overall agenda but it is vital to have a local plan to be able to deliver.

A great strength of our group is that over 50% are also working on the front line. Not necessarily all day every day, but they are seeing patients on a regular basis. For me, it has been a critical insight into how you conduct research in a pandemic environment.

What has been the focus for the group since it formed to conduct clinical trials?

What our planning group has been really focused on is a strategy for our clinical studies. We must have reviewed 30 plus proposals for clinical trials, but all too often they're all looking to recruit the same patients, and that's not possible. So, we've been doing two things. One is we've been working with senior leadership in the Medical Sciences Division to identify and prioritise those interventions that we think are most promising.

The other thing is working with the people proposing these studies to come up with constructive advice on where this intervention might fit into the care pathway of patients. For example, you have prophylaxis of healthcare workers, you have studies in general practice, studies in the emergency department, then on patients who are admitted to hospital, and studies that are done in the intensive care unit.

Now, in each of these domains you can't have 13 studies all trying to recruit the same patient, so you have to prioritise. A specific example is the Atomic 2 study. Atomic 1 was an inpatient study that would have directly competed with a national platform study called Recovery. So, we worked with the team to refocus that study, and it's now going to be focused on people who have COVID-19, attend the emergency department, but don't need to be admitted to hospital. We're going to see whether the treatment in that case can stop them needing to be admitted to hospital.

There are some good proposals that are just misplaced and we're really trying to help people with that rather than just act as a prioritisation committee. I think the insight that we bring comes not only from having clever scientists and immunologists, and people who are working on the front line, but also from a range of disciplines. It's not a pressure group for a particular organ specialty, which I think is different.

In the clinical trials to date, what are the treatments being focused on in relation to COVID-19?

Oxford is phenomenally prominent in this space.

  • The health care practitioner prophylaxis study, COPCOV, is a study led by Nick White in in Thailand, who's a Nuffield Department of Medicine (NDM) professor. This is a very large international trial that's being supported by the Diabetes Trial Unit, and there will be local enrolment.
  • The National GP platform, called Principle, is being run by Richard Hobbs and Chris Butler in Primary Care, and supported by their trials unit. So far 200 patients have been recruited.
  • The Emergency Department study, Atomic 2, is being led out of Respiratory Medicine, and the Oxford Clinical Trials Research Unit (OCTRU) at NDORMS is supporting that study which is awaiting approval from authorities.
  • Recovery is the big national platform for inpatients which has over 8000 patients recruited. It is being run by the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU) and being led by Peter Horby and Martin Landray.
  • The intensive care platform study is called Remap Cap, which is actually an international collaboration of ICU units, that Oxford is participating in.

In phase 2 we are looking at smaller studies including:

  • The Adaptive COVID19 Treatment Trial (ACTT) (led locally by Brian Angus), is an MRC/NIH study examining Remdesivir. It has completed its current enrolment.
  • A study on the effectiveness an inhaled interferon beta drug, which is just starting now.
  • We're also keen to see anti-TNF (Anti-tumour necrosis factor) tested and argue that anti-TNF should be one of the first immunomodulatory drugs tested in the next phase of our fight against COVID19.

So actually, Oxford University as a whole is making an enormous contribution, beyond all the vaccine work as well, which is very prominent.

What are the challenges of conducting trials during these unprecedented times?

I think there are a few principles here, which is that you have to keep things as simple and as consistent as you can in these clinical trials because it's a rushed and constrained environment for clinical research.

My planning group is connected directly with a prioritisation group chaired by Helen McShane and Keith Channon, which includes the leadership of Clinical Trials & Research Governance (CTRG), so that we are all focused on using our infrastructure resources to support those things that are prioritised and are the most encouraging. And the Medicines and Healthcare Products Regulatory Agency (MHRA), the Health Research Authority (HRA) and the Ethics Framework are also working very, very fast in the environment.

But we're also doing what we can locally to fast track things. The setup time has been really substantially reduced and is moving very, very fast at the moment. As an example, for Atomic 2, OCTRU has done in a fortnight what might normally take a couple of months.

Also, how long the trials take to run is an uncertain picture because, whilst there are lots of patients at the moment, by the time you're up and running are they going to still be there?

What is your personal view of the Oxford response?

In an emergency, you need coordination. And what Oxford has done is really get behind nationally prioritised work, but also that we've tried to organise ourselves locally. But that organisation is not just academics sitting in their living rooms at home, but groups who are working together across disciplines. Oxford is therefore making a very big contribution.

And NDORMS?

NDORMS is adding the resources of its Clinical Trial Unit in a prioritised way, and I am helping to coordinate that. The Department now encompasses a wide range of complementary disciplines across the clinical and laboratory sciences that are working together to deliver for patients.

One of the things I think NDORMS does well is collaborate outside its own domain, working in an open and constructive way with the right people at the right time to really deliver something important.