With Ebola nearly eliminated from West Africa, world health officials’ focus has shifted to vaccine trials and whether they can collect enough information about the effectiveness of some experimental treatments. With the end of the epidemic in sight, some experts are worried it will be too difficult to conduct ethical research on a dwindling population of Ebola patients.
The outbreak, which has killed more than 11,000 people since late 2013, appears to be on its way out. On Saturday, the World Health Organization (WHO) declared Liberia Ebola-free after 42 days without a new case of the virus. The neighboring countries of Guinea and Sierra reported seven and two cases in the first full week of May respectively.
Vaccine trials launched at the height of the epidemic last December, but WHO officials contend that human trials for two experimental Ebola treatments — the first developed by GlaxoSmithKline and the second developed jointly by Merck and NewLink Genetics — haven’t yielded sufficient data. Researchers’ sights have also turned to two drugs developed by Zmapp Pharmaceuticals and Tekmira Pharmaceuticals that they said too would produce limited results.
“It is not clear whether it will be possible to have even a hint of efficacy from these two vaccines,” Dr. Marie-Paule Kieny, WHO Assistant Director-General, said during a news briefing in Geneva. “To have efficacy we must see if people are actually protected, as the number of cases is going down it is not clear whether there will be a strong robust answer to this question at the end of epidemic.”
At this point, global health officials have placed a considerable number of options on the table in a quest to create the most effective Ebola treatment within such a short time. During a meeting in Geneva, scientists mulled over how to ethically conduct vaccine trials with so few patients. At the center of the discussion is whether to carry out a randomized controlled experiment during which patients are randomly assigned the experimental drug or a placebo, with doctors unaware of who received what. Some American and European officials believe that this trial would work best, despite a slim likelihood that the drugs’ efficacy would be proven.
But randomized, controlled, and double-bind trials aren’t without their critics, many of whom say that such testing causes harm to patients desperate to improve their condition, particularly those who receive the placebo. Some researchers have remained especially wary in the aftermath of a human trial for a drug named brincidofovir that resulted in four deaths, according to people closely familiar with the study. “We couldn’t do this in the U.S., and you couldn’t do it in the U.K., so why do you think you can you do it in Africa?” Andre Kalil, a leading Ebola doctor from the University of Nebraska Medical Center, said during an April WHO meeting.
Vaccine testing can also rely on the use of historical controls, which allow researchers to compare outcomes for those given the experimental treatment with past results. This method has drawn some skepticism among those who followed the Ebola epidemic closely. WHO’s Martin Friede said that drugs tested historically shouldn’t be the standard of care, pointing out that the data doesn’t show high efficacy. Nonrandomized trials have also been under consideration, with proponents pointing out that it’s arguably more ethical than its counterpart.
The debate about unethical experimentation in the developing world isn’t limited to the Ebola vaccine trials in West Africa. The topic has been widely discussed since the Public Citizen’s Health Research Group brought light to the phenomenon in the late 1990s. In its report, the organization brought attention to randomized, controlled trials — most of which American research entities funded — during which some HIV-positive women with child received random assignments to placebos and other treatments known to ineffective rather than the drug proven to prevent the spread of the disease from mother to baby.
Experts say that outsourcing biomedical research to developing countries has a number of advantages. First, the patients are those who would benefit from the treatment in question. Additionally, it’s highly likely that subjects haven’t taken other medication that could skew results. However, the likelihood of abuse remains likely.
An article published in The Lancet last June reached a similar conclusion, showing that more than 2,000 children in India received injections of saltwater instead of one of several widely available, effective vaccines for rotavirus, a common, life-threatening virus that causes severe diarrhea. That study was later determined to have violated international ethical standards for conducting human research.
“The continued conduct of such trials reflects a persistent, troubling disregard for international ethical principles for human subjects research, particularly research involving disadvantaged subjects in the developing world,” Michael Carome, M.D., director of the Public Citizen’s Health Research Group, wrote in Huffington Post column last year. ”Allowing such research creates a double standard that allows research using unacceptable designs to proceed in developing countries,” he added.
Despite all of the focus on developing an Ebola vaccine, Liberian President Ellen Johnson Sirleaf wants to secure her country’s long-term future, with questions of how the nation will battle the next outbreak weighing heavily on her mind. During her visit to the United States in February, Sirleaf told the Associated Press that she wants to strengthen Liberia’s medical infrastructure. Her main objectives include maintaining hospital equipment, constructing roads that allow the sick to access medical facilities, and enabling access to clean water that will stop the spread of disease.
Perhaps the issue of greatest concern for Sirleaf and others striving to prepare Liberia for another outbreak involves the death of trained medical professionals. Before Ebola struck, experts said that post-civil war Liberia needed to increase its medical personnel ten-fold to provide adequate services. Even so, many qualified Liberian doctors around the world, including Dr. James Sirleaf, the president’s son, have shown a reluctance to return to their homeland. That shortage bore some of the blame in a lethargic reaction to the Ebola outbreak in its infancy, with less than 200 doctors available to tend to more than 4 million people.
“Our own limited resources have not enabled us to take them to the level where they could be in a preventive mode. And that’s the support we want,” Sirleaf told the Associated Press. “The great lesson in all these things, you know, whether you’re dealing with conflict or whether you’re dealing with disease, is to emphasize prevention rather than cure. It costs so much when you have to fix it.”