Randomized controlled studies have advantages, but there are other valuable sources of data.
As Thomas Frieden, who directed the Centers for Disease Control and Prevention under Mr. Obama, wrote in a 2017 New England Journal of Medicine article: “Elevating RCTs at the expense of other potentially highly valuable sources of data is counterproductive.” Such limitations affect their use for “urgent health issues, such as infectious disease outbreaks.” He added: “No study design is flawless, and conflicting findings can emerge from all types of studies.”
Two randomized trials of Gilead’s antiviral drug remdesivir show how such studies can produce inconclusive results. A randomized trial in China, published in the Lancet in May, enrolled 237 patients. The study found no significant clinical benefit over a placebo, but most of the patients were severely ill when treated. Patients who had symptoms for 10 or fewer days, however, were 25% less likely to die. Similarly, a randomized National Institutes of Health trial with 1,063 patients found the drug reduced average recovery time by four days and the risk of death by 30%, but the survival benefit was statistically insignificant.
Some experts have dismissed the antimalarial hydroxychloroquine, or HCQ, even though more than a dozen observational studies have found it beneficial. A retrospective observational study of Covid-infected nursing-home residents in France, for instance, found those treated with HCQ and azithromycin were 40% less likely to die.
But a few randomized controlled trials found no benefit. A Spanish randomized trial of HCQ for prophylaxis found it didn’t reduce risk of illness among a large group of people exposed in nursing homes, households and health-care settings. Yet two-thirds of the subjects “reported routine use of masks at the time of exposure,” so they were probably less likely to be infected. Nursing-home residents, who may be less likely to wear masks, were 50% less likely to become sick if they took HCQ. But this finding was statistically insignificant, because the trial included only 293 residents.