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A steroid cut COVID deaths
A trial with many arms
A brand new pandemic left no time to develop a drug from scratch, and most of the drugs people proposed had been around for decades and were off patent. So a team at the University of Oxford, funded by the UK government's two research agencies, UKRI and MRC, and later by Wellcome and the Flu Lab, built a trial with many arms.
Every hypothesis got its own arm against a control group. Some people were sure hydroxychloroquine would prevent COVID. Others warned that a steroid like dexamethasone was too dangerous to give. By June 2020, months before vaccines, the RECOVERY trial had shown that hydroxychloroquine and some other drugs did not work and that dexamethasone did.
What changed
The team double-checked the data to be sure the result wasn't spurious before the press release went out. Within a day, the NHS changed what it gave hospitalized COVID patients, because it now knew something that would reduce their chance of death. One prominent model suggests it saved a million lives around the world within 12 months.
The cost
The trial cost an estimated $20 million. Patients already in hospital signed an extra one- or two-page form and were randomly assigned to one of the drugs in the trial, which kept the cost far below that of running separate trials at separate centers.
Why would a steroid help severe COVID?
Severe COVID often involves an overactive immune response that inflames the lungs even after the virus itself is under control. Dexamethasone is a corticosteroid, a drug class that dampens inflammation across the body. RECOVERY's results, published in the New England Journal of Medicine in 2020, showed the benefit in patients who needed oxygen or a ventilator. Patients who needed no respiratory support did not show a benefit.
How can one trial test many drugs?
RECOVERY is a platform trial, which means new treatments can join and failing ones can be dropped without starting over. Patients are randomly assigned among the available arms, and the comparison group receiving usual care is shared across all of them. Sharing it means far fewer patients are needed than in separate trials, one per drug. RECOVERY enrolled patients at hospitals across the UK.
Why did doctors fear steroids in viral illness?
Earlier experience with SARS and influenza suggested corticosteroids could slow the clearing of virus and raise the risk of complications. In March 2020, interim guidance from the World Health Organization advised against routinely giving corticosteroids to COVID patients outside of trials. That caution is why a large randomized test carried so much weight. In September 2020, after the RECOVERY result and other trials, the WHO guidance changed to recommend systemic corticosteroids for severe COVID.
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