COMMENTARY

It's Too Dangerous to Prescribe Off-Label Drugs for COVID-19

Arthur L. Caplan, PhD

Disclosures

April 21, 2020

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This transcript has been edited for clarity.

Hi. I'm Art Caplan. I'm talking to you from my home in Ridgefield, Connecticut. I'm socially isolating up here with my spouse and my dog. I have to point out that my dog has never been happier. She's getting 24-hour attention, whereas in normal times she might see a dog walker only once a day. At least some creature is upbeat about a plague.

That said, many people want to be upbeat about the plague, but they worry and wonder. President Trump said that the use of malaria drugs combined with some antibiotics is a treatment that we should all be using right away because it works. This is hydroxychloroquine and azithromycin in combination.

The president, way back on March 19, said this was a game-changer drug combination. He said, "What do you have to lose?" That we should try it because these drugs are approved as antimalarial drugs. They're just out there. We're not talking about experimental agents; we're talking about something that's approved.

I think he based some of his optimism on a paper that came out of France that was circulating around March 17, detailing 26 patients who were allegedly given this combination of drugs, some of whom got better. I think that set off panic-prescribing of the drug.

Remember, we don't know exactly what the status was of these patients. Is this something we're supposed to take to prevent us from getting infected, to prevent the virus from getting far within somebody who is infected? Or is it the emergency medicine we try and throw at somebody if they're on a ventilator and doing poorly?

It's not clear what is meant when somebody says "try it," whether it's the president or some other people in various media outlets who've been saying "use it, try it," and endorsing it. I happen to think it's a terrible idea. I think the evidence that this does anything is completely bogus.

That paper appeared in the International Journal of Antimicrobial Agents, which is a legitimate journal. It turns out that the author, a professor named Gautret, had not reported fully the results. Of the 26 people, six who didn't get better were dropped out of his report. Basically, it undermined the whole study.

The journal, under pressure, said that it was not reliable and no one should follow anything based on what this paper reported. Right away, an early report of a rather pathetic study, which turned out to be bogus completely, set off this frenzy of enthusiasm for this particular combination.

Why else would I not be in favor of this? Some doctors have said to me, "If you were dying, you'd want us to use this on you." However, my answer is "No, I wouldn't." Part of the reason I wouldn't is that you don't know the dose, you don't know how often you give it, and you don't know what you're doing.

If I was participating in a study of the drug and people said that maybe there's something to this; let's give it twice a day at a certain dose, and then we'll try it on somebody else three times a day at double the dose. That way, we start to figure out a little bit about whether this works or not. If somebody just gives it to me and a fair number of people are going to recover anyway, then I have no idea what this drug is doing in terms of facilitating improvement or cure.

The other big problem is that there are many other agents that are equally promising or more so. There is the transfusion of plasma from people who have been infected and survived. That study is underway and that seems to be an interesting idea. There are many drugs being tried to control immunologic overreactions, including interleukin drugs.

I've identified 80 agents that people have in mind, some to prevent getting infected, some to prevent the virus from getting very far if you are infected, and some as rescue or salvage interventions to see if you could be helped if you weren't doing well on a ventilator. All of those different goals have to be studied and examined.

Critics will still say that's going to take a long time. My answer to that is, no, it will take a short amount of time because we have to be willing to accept weaker evidence. I understand that we don't have a year or 18 months if we're trying to find a cure. I get it. For people who are dying, we may want to try desperate things upon them, which limits us to days or maybe a week.

If the drug and the pharmacokinetics are such that it can't even get into your body unless you have 72 hours, then what are we talking about for salvage therapies with certain drugs? If it's the case that we have no idea of the dose, frequency, or even the mode of administration, unless we organize something, would we ever really know that anything worked or whether there were adverse events from it?

The last problem with these malaria drugs is that people say, "Well, they're approved, so we know they're safe." They were approved for 35-year-olds who were going to places where there were malarial mosquitoes, to help treat malaria. They weren't approved for 75-year-olds on ventilators with underlying pulmonary problems and heart conditions.

Does anybody remember Vioxx? It's a drug that was approved, but until people started giving it to older Americans and they started to have heart attacks and die, we didn't realize that it wasn't safe for that group. In the approval process, it hadn't been tested on that group.

Just because a drug is approved doesn't mean that off-label use is safe for everyone. It certainly doesn't mean that it's safe for someone who is very fragile, very sick, and has multiple underlying conditions.

Avoid panic-prescribing. Don't hoard the drug. Don't take drugs away from people who are benefiting from them and can't get them because everybody's rushed out to hoard these things or prescribe these things. That's not how we're going to work our way out of this pandemic.

We may not be able to do randomized controlled trials for a year. We can certainly do comparative trials and adaptive trials that take weeks or months to start building some answers. If we don't build those answers, we're going to be as blind in the fight against this virus as we are today, without any further information about which way to turn or which agent might be best.

I'm Art Caplan at the Division of Medical Ethics at the NYU Grossman School of Medicine. Thank you for watching.

Arthur L. Caplan, PhD, is director of the Division of Medical Ethics at New York University Langone Medical Center and Grossman School of Medicine. He is the author or editor of 35 books and 750 peer-reviewed articles as well as a frequent commentator in the media on bioethical issues.

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