PRINCETON – It may, in the end, turn out to be fortunate that a handful of people in developed countries – four in the United States and one in Spain – have contracted Ebola. Tragic as this was for Thomas Duncan, the only one of these patients who has died, if all of the more than 13,000 cases and nearly 5,000 deaths had occurred in Africa, Ebola would never have aroused nearly as much attention in rich countries.
In this respect, Ebola is – or, rather, was – an example of what is sometimes referred to as the 90/10 rule: 90% of medical research is directed toward illnesses that comprise only 10% of the global burden of disease. The world has known about the deadly nature of the Ebola virus since 1976; but, because its victims were poor, pharmaceutical companies had no incentive to develop a vaccine. Indeed, pharmaceutical companies could expect to earn more from a cure for male baldness.
Government research funds in affluent countries are also disproportionately targeted toward the diseases that kill these countries’ citizens, rather than toward diseases like malaria and diarrhea that are responsible for much greater loss of life.
But the tiny number of Ebola cases in rich countries – and the ensuing panic-inducing headlines and quarantine measures – have brought home the global nature of infectious disease today. Mass travel has made effective containment of epidemics extremely difficult.
The best defense against an infectious disease is to fight it where it originates, and that requires good health services. Ebola appears to have been eradicated from Nigeria, in no small part because that country had a Gates Foundation-supported hospital with personnel trained and equipped to control infectious diseases. If, over the past decade or two, affluent countries had done more to assist Liberia, Sierra Leone, and Guinea, the current Ebola outbreak could have been minimized, if not prevented.
But now it is too late for that, and scientists are rushing to find both a vaccine and an effective treatment for Ebola. What ethical considerations should guide them in their search?
The standard way to judge the efficacy of a vaccine is to conduct a trial in which those who could benefit are randomly assigned to two groups, one of which receives the potentially beneficial vaccine, while the other receives a substance with no active ingredients, known as a placebo. To avoid possible confounding factors, such as greater risk-taking by those who know they have been vaccinated, or the desire of those conducting the trial to show that the vaccine works, the study is “double blind”: Neither the subjects nor those administering the trial and collecting the data know who got the vaccine and who got the placebo. Only an independent group examining the data sent in from the field has that information.
Without such a trial, the appearance of efficacy may be an illusion, because other factors would have led to a lower rate of infection anyway. Yet if a promising vaccine is available – and if safety trials in healthy human volunteers who are not at risk of infection demonstrate that it does no harm – to deny it to those who are tending to the sick and dying, at great risk to their own health, seems unethical.
That question will soon need to be answered, because both the pharmaceutical giant GlaxoSmithKline (in conjunction with the US National Institute of Allergy and Infectious Diseases) and the Public Health Agency of Canada have candidate vaccines in development.
At a recent World Health Organization meeting in Geneva, Ripley Ballou, the head of GlaxoSmithKline’s program to develop a vaccine, argued that a randomized controlled trial comparing a potential Ebola vaccine with a vaccine that protects against another virus would be the most ethical way to assess efficacy. Depending on the outcome, results could be available within three months, allowing production and distribution to go ahead with greater confidence.
Representatives of Médecins Sans Frontières (Doctors without Borders), which has more than 3,000 staff members combating Ebola in the most affected countries, strongly opposed giving placebos to anyone at high risk of contracting the disease. But Ballou appears to have persuaded many of the participants at the meeting that his proposal will save more lives in the long run. If that is true, a randomized controlled trial could be the most ethical option.
When it comes to treatment, the situation is different. In a letter published last month in The Lancet, doctors, scientists, and bioethicists from a wide range of countries – including Guinea, Ghana, Nigeria, and Senegal, as well as Britain, France, Hong Kong, and the United States – argued that a randomized trial is justified only when there is “equipoise,” or balance, between the two options offered. This can happen when doctors do not know whether a proposed treatment will do more harm than good, or when they are in doubt about which of two treatments is more likely to cure the patient.
But, when facing a disease that kills up to 70% of those who are infected, and no accepted treatment yet exists, patients could reasonably refuse consent to a trial in which they might receive a placebo, rather than an experimental treatment that offers some hope of recovery. In such cases, it might be more ethical to monitor carefully the outcomes of different treatment centers now, before experimental treatments become available, and then compare these outcomes with those achieved by the same centers after experimental treatments are introduced. Unlike in a randomized trial, no one would receive a placebo, and it should still be possible to detect which treatments are effective.