Placebo Use In Ebola Trials Unethical, Experts Say

As new Ebola cases continue to concern citizens worldwide, how to go about examining potential treatments in clinical trials has become a highly contested issue. Indeed, a panel of experts recently sent a letter into The Lancet medical journal arguing that, with a fatality rate of up to 70 percent, placebo use in Ebola trials is unethical.

According to the letter’s authors, proponents of randomized controlled trials (RCTs) say that placebo trials are customary and the only way to proceed. Lead author Clement Adebamowo and others write, “Advocates of this RCT approach state that as this experimental design will create the most robust evidence for the future, and is what regulators are used to, it is the only approach that should be considered. We disagree.”

The experts wrote that while RCTs do provide evidence and are useful in some situations, in the case of Ebola, the priorities are different. They argue the priority should be generating data on efficacy and safety as quickly as possible in order to deploy treatment, and to do so it would be best if the pharmaceutical industry, healthcare organizations, and regulatory bodies begin to consider alternative trial designs.

RCT Objections

The first objection that the experts have to RCTs regards what they call “equipoise,” or when researchers are truly uncertain that an untested treatment could provide more benefits to that of conventional care. Authors state that equipoise is a useful principle but not in a high mortality situation or when conventional care offers little benefit. As evidence, authors point to Ebola’s high mortality rate and lack of treatments with efficacy.

The authors also point out that western medical workers were not randomized to receive a placebo or zMapp, and no one would consent to receive a placebo if infected with the Ebola virus. Cancer is a good example of weighing mortality and treatments when designing trials. Regulatory bodies commonly accept evidence from trials conducted without a placebo for currently-untreatable cancers. Rules are not bent in these instances; procedures exist and are used in trials for certain diseases.

Another objection to RCTs is practical, they say. Even if randomization was ethical, it is not practical in West Africa because the population is terrified and lacks trust in their government and health care workers. Therefore, authorities have little control and cannot compel patients to consent to randomization nor can patients be expected to consent in an epidemic situation.