On Sunday, March 22, the U.S. Department of Justice announced that it was taking action in federal court to stop COVID-19-related fraud, and recommended that “Americans ignore offers for a COVID-19 vaccine, cure, or treatment.”
The very next day, President Trump tweeted about a “miracle cure” for coronavirus: Hydroxychloroquine, an antimalarial drug that has not been approved by the U.S. FDA to treat coronavirus.
Insufficient evidence
Why make the claim that hydroxychloroquine is a “game changer” for coronavirus treatment? Hydroxychloroquine and chloroquine are known to provide in-vitro protection against coronaviruses, but so far there is no peer-reviewed clinical evidence showing that it is effective against COVID-19. The hype is based on reports of success with the drug in China and a small French study that examined the effects of taking hydroxycholoroquine along with azythromysin (an antibiotic) on the viral loads of COVID-19 patients.
The study included just 42 hospitalized COVID-19 patients, with 26 given hydroxychloroquine and 16 given no treatment. After six days, the percentage of patients with no viral load detected in testing fell to about 30% in the treatment group, compared to 85% in the control group. Those treated with azythromysin as well as hydroxychloroquine appeared to do even better, with 100% showing no viral load on tests after 6 days.
Looking at this study quickly, one might agree that hydroxychloroquine is indeed a miracle cure. But on closer examination, there are serious methodological issues with the study that should make readers think twice about the results.
First, a significant portion of patients originally in the treatment group (6/26 patients) were excluded from the final analysis. Why? Three were transferred to the ICU, one died, one left the hospital, and one withdrew due to nausea. The fact that these cases were “excluded” rather than counted as failures of the treatment is suspicious.
Second, as Dr. Jason Pogue pointed out on Twitter, the patients in the control arm of the study appeared to have higher viral loads to begin with, compared with patients in the treatment arm. Therefore, it would be more difficult for them to have a zero viral load on a test, compared to patients in the treatment arm.
Why do I bring this up. Because it means there was a chunk of pts in the monotherapy arm who would need a greater antiviral effect to reach “negative” or undetectable virus. In this analysis negative was defined as Ct>35. It’s also notable that negative is often defined at Ct>40.
— Jason Pogue (@jpogue1) March 20, 2020
What’s the harm in hype?
We do not have strong evidence that hydroxychloroquine helps COVID-19 patients, but that does not mean that it cannot help them. If this drug has the potential to help in this pandemic, what’s wrong with bringing attention to it?
It is just as likely that giving COVID-19 patients hydroxychloroquine could harm them as help them. Hydroxychloroquine has several side effects, including–in rare cases–fatal cardiac failure. Exposing patients to these side effects without evidence that they will benefit from the treatment is risky.
Misleading claims about COVID-19 cures can also lead to people hoarding drugs or harming themselves by taking drugs without medical supervision. Unfortunately, many such events have already happened as a result of Trump’s actions. Overdoses of chloroquine have been reported across the world. An American couple ingested chloroquine phosphate, a chemical typically used to clean fish tanks; the woman became seriously ill and the man died.
Those who need hydroxychloroquine for indicated conditions like lupus or rheumatoid arthritis are having trouble accessing their medications. For these patients, “stopping the medication could cause them to flare, which means that they then need to go on other immunosuppressants … or even get admitted and potentially get exposed [to the coronavirus] in the clinical setting,” said Brigham and Women’s rheumatologist Dr. Jeff Sparks, in a WBUR interview.
Ironically, hype about this drug may make it more difficult to find out whether the drug really works. As hospitals start clinical trials to test the effects of hydroxychloroquine for COVID-19, it may be harder to recruit patients to be randomized, if they already believe that the drug is effective.
Not having a vaccine or a cure is scary, but now is not the time to throw evidence out the window. As Dr. Ezekiel Emanuel and Dr. Vinay Prasad wrote in a recent op-ed in The Washington Post, “When it comes to fearsome, fatal conditions, it is human nature to try something because it should help, because it might help, because it must help, or because it couldn’t hurt. But often it does harm people and our quest for a real cure.”