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Why using unproven Ebola medicine is bad science

Relatives weep as a Liberian health department burial team prepares to enter the home of a woman suspected of dying of the Ebola virus. Some say these desperate times should not call for desperate measures.
Relatives weep as a Liberian health department burial team prepares to enter the home of a woman suspected of dying of the Ebola virus. Some say these desperate times should not call for desperate measures.
John Moore

This week, the World Health Organization announced that it is ethical to give untested drugs to Ebola sufferers in what is the worst-ever outbreak. The announcement came after uneasy questions about Ebola medicine emerged following the treatment of two Americans with the experimental drug ZMapp. Some critics asked why Africans didn't have the same access.

Wider use of experimental medications, the WHO said, could be helpful at a time when there are no approved treatments or cures for Ebola. But not everyone agrees. Dr. Philip Rosoff, who specializes in clinical ethics at Duke University, says he's concerned that the decision to test experimental drugs during this outbreak may hurt more people than it helps. Here's a transcript of our conversation.

Julia Belluz: The WHO endorsed the use of experimental treatment in this outbreak, but you disagree with that decision. Why?

Philip Rosoff: If you read the WHO release on the ethics of using these drugs, they emphasize a couple of points: it should be okay to use them, but informed consent should be gotten. That seems to be self-evident but I'm not sure what informed consent means under situations of such desperation when a drug that's never been used in people is held out as a life saver.

JB: Some might say that's a necessary evil: One of the main reasons for approving the use of these medicines was that, with proper data collection after they're given out, we may be able learn about whether they work and we'll potentially have more tools to help people in future outbreaks.

PR: That's the second problem: the WHO talks about collecting data but that's going to be almost impossible to do. It'll be impossible to decide whether it's effective or not because it's not going to be used under controlled circumstances. When people get better, we'll have no idea whether it was because people are using the drug, or if somebody dies after getting the drug you don't know whether it's the disease or the drug. Because these patients are so sick, it may not be possible to detect side effects that you could under more controlled circumstances.

All of these drugs have never been tested in humans. Animal experiments are good and important to do prior to testing in humans. But they're only of limited value. Only a small percentage of drugs that start being tested in labs as potentially interesting finally make it to being approved as safe and effective by the Food and Drug Administration.

"Desperation doesn't necessarily breed good science or good medicine."

JB: Are you concerned about precedent — that we could be rushing to this decision, and if all doesn't go well, it may set a low bar for how we handle future outbreaks?

PR: I think people have been rushing a little too quickly and not thinking about some of the more complex and intricate issues that are raised by this situation. I think that if this goes forward, and people start using this drug and we make a precedent that we're going to use highly experimental, never-before-tried drugs in desperate situations, then we might make more mistakes than see benefits.

Desperation doesn't necessarily breed good science or good medicine. I think desperation breeds desperate measures that aren't the best measures.

JB: You've also mentioned a concern that there may be challenges with deciding who gets treatment. Can you explain that?

PR: Because the outbreak is mostly occurring in Africa, there's a rationing problem. If you are going to use this drug, who should get it? There's quite a bit of controversy about the fact that three people who have gotten [ZMapp] are all Caucasian, all from western countries. None of the people most affected by the outbreak have received this drug. So are all these people equally deserving of this particular drug since we don't know anything about who it might work better with?

There is a long and sordid history of western pharmaceutical companies doing clinical trials in Africa and subjecting Africans who are poor or under-educated to experimental drugs that would never be used there be used on  westerners. Luckily there are conventions that have eliminated that activity. On the other hand, people are concerned that the three people treated so far are from wealthy western countries and not those that are most affected. Either way, this brings up memories about the bad old days.

JB: Another justification for sanctioning the use of unproven drugs is that they're better than the alternative — near certain death from Ebola. Supporters of the use of experimental treatments say that doing something is better than nothing.

PR: I say the question is whether we're actually going to be able to learn anything using this drug in such a spotty way without any kind of control groups. I suppose you could say that you have historical control groups: you know a certain percentage of people who contract Ebola die. If you use this drug in a large enough group of people, you could compare that with a historical control.

But there's any number of problems with that. If this were a uniformly fatal disease where virtually everyone who got it died, you could make a case that you should be able to learn something. But with good, supportive care a reasonable percentage of people with Ebola do live through this.

There's going to be bias in terms of who you decide to put on the drug. For instance, one of the nice things about a randomized trial is that the people who decide who goes on the drug don't have any power over who gets placebo and who gets the drug. If you decide to leave it up to treating physicians, there may be a hidden bias that they should only give it to people who are getting better anyway. And then you may mistakenly assume that the drug is efficacious, but it is not.