12 Aug 2014

Ebola, ZMapp And Ethics Of Drug Distribution - by Arthur Caplan

What should happen if a massive viral outbreak appears out of nowhere and the only possible treatment is an untested drug? And who should receive it? The two American missionaries who contracted the almost-always-fatal virus in West Africa were given access to an experimental drug cocktail called ZMapp. It consists of immune-boosting monoclonal antibodies that were extracted from mice exposed to bits of Ebola DNA. Now in isolation at an Atlanta hospital, they appear to be doing well.

It’s an opportunity the 900 Africans who’ve died so far never had. Is there a case to suspend ethical norms if lives might be saved by deploying an experimental drug?

The reasons for different treatment are partly about logistics, partly about economics and, partly about a lack of any standard policy for giving out untested drugs in emergencies. Before this outbreak, ZMapp had only been tested on monkeys. Mapp, the tiny, San Diego based pharmaceutical company that makes the drug, stated two years ago: “When administered one hour after infection (with Ebola), all animals survived…Two-thirds of the animals were protected even when the treatment, known as ZMapp, was administered 48 hours after infection.”

But privileged humans were always going to be the first ones to try it. ZMapp requires a lot of refrigeration and careful handling, plus close monitoring by experienced doctors and scientists—better to try it at a big urban hospital than in rural West Africa, where no such infrastructure exists.

And because of the drug’s experimental nature, it’s unclear that it should go to anyone else. Even if the drug is cooled correctly, success in a few monkeys (less than 20) tells us little about what will happen in a lot of humans who’d had the infection for more than two days. No one knows how much drug to give, how often, what other pre-existing medical conditions might influence its efficacy or even what route is best, be it IV, pill, syrup, or even surgically right into the liver. With an untested drug, there is always a chance you will kill the first human subject who might otherwise have lived. And the two Americans who got it in Africa had been infected for more than a week, making its efficacy completely unknown. Still, because they are a small group in such a carefully controlled setting, they are better candidates for the drug than others might be.

But it’s about more than logistics. Drugs based on monoclonal antibodies usually cost a lot—at least tens of thousands of dollars. This is obviously far more than poor people in poor nations can afford to pay; and a tiny company won’t enthusiastically give away its small supply of drug for free. It is likely that if they were going to donate drugs, it would be to people who would command a lot of press attention and, thus, investors and government money for further research—which is to say, not to poor Liberians, Nigerians or Guineans.

The medical missionaries got the experimental drug because the evangelical Christian international relief organisation they work for, Samaritan’s Purse, reached out to the US Centre for Disease Control and the NIH to find out if there was any drug to give to them. They were referred to Mapp Pharmaceuticals and evidently struck some kind of deal to get the drug to their employees who were in Africa at the time. (Technically, African health ministries could make a similar request.) The Food and Drug Administration has little oversight over what goes on abroad, and the federal government has no programme to consider appeals for use—much less payment—of experimental drugs that have only been tried on animals. Without an organisation pushing, no one might have received access to any sort of treatment. The chance of a poor African getting an experimental drug is about the same as Donald Trump contracting Ebola (which is apparently his greatest current fear).

Even if logistical and economic obstacles could be surmounted, is there a case for giving ZMapp to Africans still dying from Ebola? Many Africans were infected more recently than the Americans now being treated in Atlanta, so they better fit the conditions in which the drug was tried in the monkey lab.

But there is no accepted set of rules for a sick person to request compassionate access to drug that is experimental, expensive, and in short supply. And access to experimental drugs remains a long shot full of risk. While the American Ebola patients gave their consent, and while most people would want to do something rather than nothing, the decision about gaining access is more in the hands of the drug manufacturer than the would-be subject. The dying may feel more cavalier about entering a drug experiment—the rewards (life) could justify the risks (since death approaches anyway)—but a company may still withhold a drug from a willing volunteer for fear that it will fail and reduce investor interest or increase attention from malpractice attorneys.

An ethical case can surely be made for an organisation that puts health-care workers in harm’s way to acquire access to experimental drugs and bring staff home to get the best possible care. But that is neither a fair nor just policy for deciding what to do when an emergency arises and rationing is the only option. This Ebola outbreak has taught us two things: That we need to act quickly to shut down emerging epidemics wherever they occur, and it is long past time to have a transparent public policy about what to do when not everyone gets a chance to live.

Arthur L. Caplan is the director of the Division of Medical Ethics at New York University Langone Medical Centre’s Department of Population Health.

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