Was it ethical to give two Americans an experimental Ebola therapy?

by Tom Ulrich on August 12, 2014

Ebola response ethics experimental treatment therapy ZMapp

Guinean Red Cross volunteers prepare to decontaminate a hospital in the capital, Conakry. (European Commission DG ECHO/Flickr)

The world paused for a moment when the news broke last week that two Ebola-infected American missionaries working in Liberia had received an experimental therapy called ZMapp. As I write this, both patients are back on U.S. soil, and seem to be responding well to the treatment.

But was it ethical?

That difficult question can be divided into two. First is the question of whether it was ethical to give the two patients a drug that, up to that point, had never been tested in people. The second—in some ways thornier—question is: Was it ethical to give the treatment to two Americans but not the nearly 1,850 West Africans infected in the outbreak (as of August 11)?

First, do no harm

Aaron Kesselheim, MD, JD, a physician and health policy researcher at Brigham and Women’s Hospital who studies drug development, notes that there is a long history of ethical debate around providing patients experimental drugs on a compassionate or “expanded access” basis, as was the case with the two U.S. missionaries. ZMapp’s developer, Mapp Pharmaceuticals, had carried out animal experiments, but had no clinical data on whether the treatment was safe, never mind effective.

“If a person with a life-threatening condition has no other choices and there is some scientific rationale for this product working, some have argued that patients have a right of personal autonomy to try anything they can to help themselves,” Kesselheim says.

The problem, he adds, is that a patient requesting compassionate access to a drug can’t simply say, “I demand the therapy and I shall have it.” “There are lots of practical considerations that can serve as barriers,” he says, citing production, delivery, administration and patient monitoring that need to be addressed. And indeed, as the CDC notes in an FAQ about the outbreak, there is only a “very limited supply” of ZMapp.

Ebola virus ethics experimental treatment therapy ZMapp

The Ebola virus. (CDC)

Richard Malley, MD, an infectious disease expert and vaccine researcher with Boston Children’s Hospital, notes that for a disease as rare and rapidly fatal as Ebola, a critical situation may provide the only good opportunity to study a treatment.

“It’s a very difficult situation,” he explains. “Ebola is so rare, lethal and unpredictable that this would be a situation where an experimental drug would be used in less-than-ideal situations.”

Malley adds that when patients understand the risks and can give consent, and adverse effects can be monitored to the extent possible, it is reasonable to use an experimental therapy. His words mirrored those of an ethics panel convened by the World Health Organization (WHO), which announced in a statement this morning that “it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.”

But, he cautions, as with any experimental therapy, questions about ZMapp’s efficacy and potential safety risks should not be glossed over. Dire situations like the one in West Africa “should never in any way alleviate the responsibility of the scientific community to figure out a way to study a medication and determine whether it is efficacious. And constant monitoring for safety issues is critical.”

Why Americans and not Africans?

This second question has, in some ways, been the more contentious one. As a journalist from Sierra Leone, Winston Ojukutu-Macauley, reportedly asked, “If Americans had this serum all the time, why didn’t they send it to us Africans to help save lives?”

This question has appeared in several stories and editorials in the scientific and mainstream media for the last few days. And it is certainly echoing loudly through the halls of the WHO, which last week declared the outbreak an international public health emergency.

Ebola response ethics experimental treatment therapy ZMapp

A Guinean Red Cross volunteer talks to local residents about the risks of Ebola and how they can protect themselves from the virus. (European Commission DG ECHO/Flickr)

Malley says that the authorities that make decisions like this are stuck between a rock and a hard place.

“Imagine the situation in reverse,” he says. “A U.S. company makes an experimental drug. We only know it has preclinical efficacy, and the first humans to receive it are from West Africa. Now you’re open to criticism that West Africans are being used as test subjects for an experimental drug of unclear safety and benefit.

“It’s a difficult situation,” he adds. “And in some ways reasonable criticism can be raised one way or the other.”

Kesselheim wonders what the next steps should be as we learn from the experience of the two Americans. “If it turns out that this is a promising treatment, what’s the most ethical and efficient way of making it available to the people in Africa who need it?”

And ignoring for a moment the fact that supplies of the treatment are so low as to be nonexistent, who gets to be first in line if more becomes available? Local clinicians, many of whom have become infected themselves? Foreign aid workers? The young, the old, the newly diagnosed? These are questions the WHO ethics panel addressed only so far as to say that there needs to be more discussion.

But this important ethical debate shouldn’t distract from the fact that we still don’t know whether ZMapp works, cautions Malley. “Hopefully this helps pave the way for starting a real clinical trial and working toward a treatment that will have real benefit,” he says. “Unless we can start evaluating medications like this in a rigorous fashion we’ll be having conversations like this for years to come.”

To learn more about the ethical debates swirling around these questions, we recommend reading:


Leave a comment

Previous post:

Next post: