Britain wins rare praise for leading race to test life-saving Covid drugs

It has been a startling week for those following Britain’s response to the pandemic. Roundly derided for the lateness of its lockdown and its bungled testing programmes, the UK was the unexpected recipient of a sudden bout of lavish praise for its scientists’ efforts to combat the d isease.

“The Brits are on course to save the world,” wrote leading US economist Tyler Cowen in Bloomberg Opinion, while the journal Science quoted leading international scientists who have heaped praise on British researchers’ anti-Covid work.

And the prime target for these plaudits has been the UK’s Recovery trial, a drug-testing programme that has involved input from more than 3,000 doctors and nurses working with 12,000 Covid-19 patients in 176 hospitals across the nation – from the Western Isles to Truro and from Derry to King’s Lynn. These trials were carried out in intensive care units crammed with the seriously ill, patients whose numbers were boosted to high levels because of the UK’s late pandemic lockdown. The results have nevertheless changed Covid-19 clinical practice across the planet.

A cheap inflammation treatment has been found to save the lives of seriously ill patients while two much-touted therapies have been shown to be useless at tackling the disease. No other nation has come close to matching these achievements.

“It has been an extraordinary four months,” says one of Recovery’s founders, Martin Landray of Oxford University. “And yes, it is something that the UK can be proud of.”

Landray is an expert in setting up large clinical trials while his co-founder, Peter Horby, also of Oxford University, is an infectious disease specialist who was involved in Covid drug trials in Wuhan last winter when the pandemic first emerged. However, these studies ended when case numbers plunged as the Chinese authorities applied their rigid lockdown. “At the same time, cases began appearing in Europe and I realised we need to start work here,” says Horby.

So he and Landray joined forces and set up Recovery, short for Randomised Evaluation of Covid-19 Therapy. “We realised doctors would soon be looking for treatments once cases started pouring in to our hospitals,” says Landray. “If we didn’t quickly start trials, we would never know if the drugs that we used were any good. We had about two weeks to get a programme up and running before the tsunami hit the NHS.”

The pair took nine days from drafting their first protocol to enrolling their first patient. “Normally it takes nine months to do that,” says Horby. “For good measure, we enrolled 10,000 patients within eight weeks.”

Randomised drug trials are the gold standard for pinpointing useful medicines, removing unconscious biases that can cloud clinicians’ judgments. Thousands of people are given a drug or a placebo. No one knows which they are taking. Then results are compared and the efficacy of the treatment is revealed.

Crucially, these trials need very large numbers of patients and no single hospital has enough for such research. Britain has one key advantage, however, in that it has a centralised National Health Service. Other nations, in particular the US, have health services that are fragmented. “It’s the infrastructure in this country – the NHS and the National Institute of Health Research, who funded Recovery – that has made this possible,” says Horby. Three months after setting up their operations, Recovery produced its first results. The first was for the anti-malarial drug hydroxychloroquine, which was then being widely touted by politicians such as Donald Trump, Emmanuel Macron and Jair Bolsonaro as an effective Covid-19 treatment. All believed it could save the world.

The Recovery team disagreed, however. Their trials showed hydroxychloroquine provided no help to Covid patients of any kind. Ten days later, the drug’s Emergency Use Authorisation in the US was withdrawn – to the disgust of Trump.

It was an important development, says Landray. “It meant hospitals around the world no longer needed to waste resources on a useless treatment, and could stop falsely raising patients’ expectation.”

Then there was the combination therapy of lopinavir and ritonavir, two anti-HIV agents, which was also being touted as a powerful Covid treatment. Recovery compared 1,596 patients who were given the drugs with 3,376 who were not – and found no significant difference in death rates between the two groups. It was another disappointment.

Finally, Recovery turned to dexamethasone, a cheap steroid used to counter inflammation and treat arthritis. This was shown to reduce deaths by a third among patients on ventilators in intensive care units. “This is a drug that costs £5 a course – next to nothing – and is widely available,” says Landray. “It was an incredible surprise and a huge step forward.”

As a result dexamethasone has been added to the clinical guidance notes for treating severely ill Covid-19 patients in hospitals around the world while lopinavir and ritonavir as well as hydroxychloroquine have been removed. “Clinicians come up with all sorts of hypotheses about the usefulness of drugs,” says Landray. “But you’ve got to test these hypotheses and to do so you need large, randomised trials.”

The value of this approach has been noted on the other side of the Atlantic. Recovery’s three trials are the best to have been performed anywhere in the world, Eric Topol, director of the Scripps Research Translational Institute told the journal Science this month.

Two other, far sadder, impacts have also influenced Recovery’s success, however. “Firstly, we had a very big epidemic in the UK and so had a lot of patients who we could recruit,” says Horby. “The other was the high death rate among those who were hospitalised, around 25%. If that mortality rate had been only 5% we would have needed an even larger trial to produce meaningful results.”

Current trials are now focusing on three other candidate treatments: an antibiotic called azithromycin, an antibody called tocilizumab and a treatment known convalescent plasma – blood plasma that is taken from people who have had coronavirus and which will contain antibodies that might help those who are seriously affected by the virus. However, Horby and Landray say it may take months to get results from these results. “Fewer people are now being hospitalised – which means fewer people are now being recruited to Recovery,” says Landray. “That means results which were rapidly achieved a few weeks ago will now take longer. It’s good news, really.”