Guilherme: “16 June 2020. Evening TV news shows across the world were suddenly opening with the result of our research, and rightly so. Dexamethasone was the first drug to be shown to save the lives of people infected with Covid-19. To a young researcher like me, that day felt like being part of history. It was a gift from the UK to the world.”
Two years ago, the Recovery trial transformed the care of Covid patients with its dexamethasone announcement. Within four hours, the steroid was included in NHS treatment recommendations. Almost overnight, treatment of Covid patients around the world changed completely. It has been estimated that dexamethasone may have saved a million lives in the first nine months following the announcement.
Recovery, jointly led by Oxford Population Health and the Nuffield Department of Medicine, is a groundbreaking scientific machine which, from the outset, moved at unprecedented speed. Within 15 days, more than 1,000 participants around the UK had joined the trial; five weeks later, that number had risen to 10,000. In the first 100 days alone, the trial produced three groundbreaking results that would completely reshape Covid care.
From an impromptu discussion between two professors on a London bus to headlines around the world – and a baby being born at home in the midst of the pandemic – this is the inside story of Recovery, by three medics who have been part of this extraordinary journey.
The vast and unique nature of the NHS provided the perfect setting for the trial’s rapid development. Indeed, if a similar approach could now be employed for other common and important diseases, we believe it could transform the quality of evidence supporting treatments for millions more people in the UK and around the world.
How it all began
Mark: “Working on hospital wards during the first wave of the pandemic was at times a haunting experience. Patients of all ages were severely ill, and could deteriorate rapidly with little warning. I spent many hours talking to patients at their bedside and to their relatives on the phone – not knowing when the last conversation might be; wanting to offer hope but not false hope. The emotional toll was profound, but the privilege of being there for patients and their families at such a terrifying time was enormous.”
Early March 2020. Despite growing concerns about the worldwide spread of Covid-19, life in the UK continued pretty much unchanged. Daily commuting, large sporting events and international travel all kept going, even after the virus began circulating within the UK and the first deaths occurred.
But in scientific circles, discussions were already underway about how to respond to this mysterious virus. Following a call for research proposals in early February, public funding for a UK-based trial was agreed on 5 March.
Four days later Professor Martin Landray, an experienced clinical trialist based at Oxford Population Health, and Sir Jeremy Farrar, director of Wellcome, happened to meet on a No 18 London bus journey. Both agreed that a major public health crisis was looming.
“What we agreed on that bus trip was that the tsunami would arrive within a fortnight,” Landray later recalled. “So we had to have the trial up and running within two weeks.” On 11 March , the World Health Organisation declared Covid-19 a global pandemic, and on 23 March, the UK imposed its first national lockdown.
Landray joined forces with Professor Peter Horby, a specialist in emerging infectious diseases at the Nuffield Department of Medicine. They recognised that Covid-19 was an entirely new disease for which no proven treatments were available. Many were making educated guesses regarding what did and didn’t work, resulting in a jigsaw of different clinical recommendations around the world, but no one knew much for certain.
And so Recovery (short for the Randomised Evaluation of Covid-19 Therapy) was established to embrace, rather than deny, these uncertainties – and to harness the best scientific methods to resolve them, rather than relying on hype or hope.
But this mantra did not land well with some people, who mistook scientific rigour and the quest for definitive answers for dangerous delaying tactics, thinking they already knew which treatments would and wouldn’t work. As Horby later recalled: “I’ve got a drawer full of letters telling me I’m killing people.”
The guiding principles of Recovery
Recovery team members Mark Campbell, Guilherme Pessoa-Amorim and Leon Peto
Leon: “I was working on the Infectious Diseases ward at Oxford’s John Radcliffe Hospital in March 2020 when I first heard about the Recovery trial. In over a decade working in hospital medicine, I had never known a trial that felt accessible to normal clinicians, but Recovery was different. Involvement of medical teams was encouraged and made easy.
“Already, various drugs had been proposed as treatments for Covid19, but there was no good evidence that any of them actually helped. We knew that by randomising participants, we would discover if any of the drugs being tested actually did anything. In those early days, I remember that many of us thought dexamethasone was the least promising – until June 2020, when we were delighted to be proved wrong.”
To be successful, Recovery needed a mechanism for conducting randomised controlled trials at a scale large enough to provide conclusive evidence. Unless the number of patients involved in such a trial is large, the play of chance can mean sicker patients are more common in one group, masking any effect of the treatment being tested (in the same way you need to toss lots of coins for the number of heads and tails to be reliably balanced).
Thousands of patients had to be enlisted as soon as possible. This was no trivial task – especially given the immediate impact of the pandemic on clinical research due to staff shortages and redeployment. Healthcare workers were under unprecedented strain, and there was little room for additional research commitments.
We knew that by randomising participants, we would discover if any of the drugs being tested actually did anything. In those early days, I remember that many of us thought dexamethasone was the least promising
It has been estimated that dexamethasone may have saved a million lives in the first nine months
