Why caution is critical in using unapproved Ebola drugs on humans

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Amid reports of protesters breaking into a holding center in Liberia and carrying away Ebola patients, the current outbreak in Western Africa threatens to transform from a local and contained problem to a pandemic with potential worldwide ramifications.

To combat the spread of this deadly disease, which is easily passed from person to person through close contact with blood or bodily fluids, several Western companies are in the early stages of developing both vaccines and therapeutics. Even though none of the drugs has been tested in humans for safety or efficacy, the ongoing epidemic is exerting pressure on regulatory authorities to quickly advance this process.

Last week the World Health Organization issued an emergency bulletin stating that because of the circumstances surrounding the Ebola crisis, if certain conditions are met, “it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.”

One company – Mapp Biopharmaceutical Inc. – has created a biologic drug called Zmapp that in the laboratory appears to neutralize the Ebola virus, showing promise as an effective treatment. However, it had never been given to humans until it was administered to three Ebola patients – two Americans and one Spaniard – who contracted the disease while working with others sick with Ebola and more recently to three African patients, exhausting the supply.

It may seem reasonable to bypass the normal regulatory pathways to demonstrate both safety and efficacy for this drug and take the chance that it might work. But despite these desperate circumstances, caution should be paramount when approving the use of an unproven drug because:

1Desperation often gives rise to ill-considered choices both on the part of doctors and others caring for the very sick, their families and the patients themselves. Holding out the hope of a treatment, irrespective of how that hope is couched with caveats, is likely to prove irresistible to those frantic for any chance whatsoever, making the idea of informed consent meaningless.

2There are many examples of drugs that looked promising in nonhuman animals only to prove ineffective and/or dangerously toxic when given to people. Unfortunately, giving Zmapp to patients under these conditions will not permit us to find out if it is effective, overly toxic or completely ineffective and nontoxic. It would be a tragedy to discover later that we held out hope and poured energy into developing a drug that didn’t help anyone or, worse, hurt them.

3 Western pharmaceutical companies have had a long and unsavory history of carrying out drug trials in African populations – typically in poor and undereducated people – only to take the data they generate to market medicines to be sold in wealthy countries and not benefit the people whose sacrifice made this possible. These practices have changed dramatically over the past 10 years or so, but memories die hard, and this is still a sensitive issue. When Zmapp was given to three Westerners and not Africans, it recalled past discriminatory actions. There should be a proportionate distribution of both the burdens and the benefits of any intervention and research.

4Finally, even under the best of circumstances, it is unlikely there will be sufficient Zmapp (or some other medicine yet to come) to treat all infected with Ebola. Therefore, decisions must be made about who should receive the extremely limited supply.

No matter how this is decided, insufficient time and thought have been devoted to creating a fair and equitable system to distribute the potential and questionable benefits of this experimental therapy.

The outbreak of Ebola represents a tremendous challenge to fragile public health systems, to poor countries whose populations were already suffering from poverty and other ills, and to those charged with attempting both to treat the sick and prevent the spread of the virus. Nevertheless, we must not be so frightened that we fail to give due regard to the difficult ethical questions raised by this harrowing situation.

It is bad enough that so many people are dying. We should not compound the grievousness of their plight and come to regret that they suffered even more for avoidable mistakes.

Dr. Philip M. Rosoff is professor of pediatrics and medicine at the Trent Center for Bioethics, Humanities and History of Medicine at Duke University Medical Center in Durham.