In a video that went viral yesterday, Dr. Stella Immanuel, a primary care physician in Houston, declared that no one need fear the coronavirus that has so far killed more than 150,000 people in the United States and more than 650,000 worldwide.
“This virus has a cure. It is called hydroxychloroquine, zinc, and Zithromax.”
Dr. Immanuel made these remarks together with other doctors in front of the U.S. Supreme Court building in a video produced by Tea Party Patriots, a political group. They argue that the American public has been duped by a broad disinformation campaign designed to suppress facts about hydroxychloroquine, the malaria drug touted by President Trump as a treatment for COVID-19. The drug, they say, is effective.
This is a bold claim. Is it accurate? The doctors admonish their listeners not to take the word of experts but do their own reading on the evidence. In that spirit, here’s a rundown of what is known.
To start, Dr. Immanuel referred to a 2005 study, which alerted her to the potential of hydroxychloroquine as a treatment against COVID-19. In the study, published in the Virology Journal, researchers looked at the effect of the drug on cell cultures of primates and found that it inhibited the SARS virus. That’s interesting, but it’s a long way from a COVID-19 treatment. For one thing, a great deal of additional testing would need to be done to establish a benefit to humans. Also, although SARS is similar to SARS-CoV-2, they’re not the same virus.
Fortunately, there’s better data available. So far, several studies have been published on hydroxychloroquine and COVID-19 that use the gold-standard for medical science: the randomized clinical trial. How a drug performs in a randomized trial is the best way to know whether it is really working.
Ideally, a test measures one thing only. If you’re testing the effectiveness of a drug, you need to know that only the drug is affecting the outcome and nothing else is interfering. When scientists design a study, they test two groups of patients. One group (the treatment group) gets the drug, the other group (the control group) doesn’t. To avoid bias, the patients don’t know which group they’re in. Neither do the doctors who administer the drug.
Randomization is the key to making sure the treatment group and the control group are as identical as possible. For instance, since young people are more likely to survive COVID-19, you don’t want them over represented in either group. Randomly choosing which patients go in the two groups ensures that this is not likely to happen. Size is also important: the bigger the two groups, the more likely they are to be identical, just as a coin flipped a thousand times is more likely to come up heads half the time than a coin flipped twice.
When the coronavirus struck, there were no randomized control trials available for any drug or treatment. Still, sick patients showed up in emergency rooms and doctors had to treat them. They tried various available drugs, including hydroxychloroquine. Having long been used to treat malaria and lupus, it was known to alter the immune system. Perhaps it could have some benefit to COVID-19 patients, many of whom were going into respiratory distress because their immune systems were overreacting to the virus.
As doctors were using the drug, they were also studying it. Not all of them were randomized trials, however. Some, out of necessity, were observational studies—doctors were treating patients with hydroxychloroquine, seeing how well they responded and writing up the results so other doctors could benefit from what they’d learned. In April, one such observational study gave researchers hope that the drug might be effective against the new disease. It took place in a hospital in France, where doctors gave 20 patients hydroxychloroquine and compared their progress to other patients who refused the treatment. Doctors did not randomly select patients for each group and they only tested a small number of patients. They reported a positive response.
At about the same time, doctors in a hospital in Wuhan assigned 62 patients randomly to control and treatment groups. They found that the group that received the treatment did better than the control group.
Based on these two studies, hydroxychloroquine became a household word. President Trump began to tout the drug as a possible treatment. The FDA authorized the drug for emergency use, which meant that the U.S. would stockpile and distribute it.
More evidence fell into place in May. Two big studies turned up no effect. One study, of 1446 patients, appeared in the New England Journal of Medicine; the other study, of 1438 patients, was published in the Journal of the American Medical Association. This lent support to the National Institutes of Health’s recommendation that hydroxychloroquine be used only in clinical trials and not in routine care. Although both studies were peer-reviewed and considered robust, they were observational, and thus far from definitive.
During this time, Dr. Anthony Fauci, in White House briefings, was cautioning that rigorous testing was needed to know if the drug actually worked. Two big randomized trials were underway, which scientists hoped would provide solid evidence one way or the other—a large study in Nashville and another in the UK.
In June, the National Institutes of Health announced that the Nashville study, which had enrolled 470 patients, had stopped taking on new ones. An independent review board had reviewed the data and concluded, “while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with COVID-19.”
The other big randomized trial met a similar fate. After signing up more than 11,000 patients from 175 hospitals in the UK, an independent committee examined the data and concluded that “there is no beneficial effect of hydroxychloroquine in patients hospitalized with COVID-19.” They, too, stopped enrolling new patients. Neither the Nashville study nor the UK study have been published in peer-reviewed journals—their status was announced in press releases.
Hydroxychloroquine was sputtering in other studies, too. On the question of whether the drug administered before symptoms could serve as an effective prophylactic, a randomized study of 821 patients published in the NEJM in June came up empty-handed. “After high-risk or moderate-risk exposure to COVID-19, hydroxychloroquine did not prevent illness compatible with COVID-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.” Another randomized trial, involving 150 patients in China, also found that the drug showed no benefits.
On June 15, the FDA revoked authorization of hydroxychloroquine for emergency use. “Our actions will be guided by science,” said Dr. Anand Shah of the FDA in a statement.
More recently, a randomized study in the U.S. of 491 patients, published in July in Annals of Internal Medicine, showed negative results for an oral administration of the drug to patients with mild symptoms who were not hospitalized. Their conclusion: “Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19.”
Six months into the pandemic, the gold-standard evidence on hydroxychloroquine is beginning to mount, and it’s not looking good. Meanwhile, the spotlight on hydroxychloroquine soaked up a disproportionate share of NIH research funds. Between April 1 and June 15, the NIH spent nearly $11 million studying the drug compared to $1.3 million on a vaccine.
Dr. Immanuel claims to have “personally treated over 350 patients with COVID,” including those with underlying conditions, and “we’ve not lost one.” That would be considered just another observational study—if she were to document it and publish it in a peer-reviewed journal.