This morning the Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) resumed consideration of U.S. engagement in the global response to the current Ebola epidemic by examining ethical issues that arise when conducting research during a public health emergency.
As experts move to accelerate development of drugs and vaccines against Ebola, a debate has emerged over whether these therapies should be evaluated with the placebo randomized control approach. This type of research involves clinical trials in which one group of volunteers receives the actual vaccine or drug candidate and another group receives a placebo.
Many clinicians consider the placebo-control approach to be the gold standard for determining the efficacy of a new treatment. But tension in western Africa today involves how scientists and policy makers should prioritize humanitarian and scientific concerns as they address both the immediate crisis and seek evidence that can be applied to future outbreaks.
Clement A. Adebamowo, B.M., Ch.B., F.W.A.C.S., F.A.C.S., Sc.D., a Professor of Epidemiology and Public Health at the University of Maryland School of Medicine, told members of the Bioethics Commission that the placebo-control approach provides very strong evidence. But Adebamowo, who was closely involved with Nigeria’s Ebola response as chair of Nigeria’s National Health Research Ethics Committee, said Nigerian health authorities have concluded there are instances in which other approaches may be warranted.
“We believe that these things should not be taken as doctrinaire positions,” he said. “That is why the Nigerian ethics committee issued the guidance statement saying we are going allow the use of therapies that have not completed the standard clinical trial development pathway in the context of this epidemic and share the data with all so we can rapidly evaluate the efficacy of these interventions.”
Luciana Borio, M.D., Assistant Commissioner for Counterterrorism Policy and Director of the Office of Counterterrorism and Emerging Threats at the U.S. Food and Drug Administration (FDA), said that there is an ethical case to be made for conducting a placebo-control trial even in the midst of a major disease outbreak like the Ebola epidemic in western Africa. While some have questioned the ethics of giving a placebo to research subjects at high risk of being exposed to Ebola, Borio said that one could argue that conducting a trial without a placebo control is unethical if it is not going to determine treatment efficacy.
“In the case of Ebola, (such a trial) would be scientifically invalid and a scientifically invalid study by definition cannot be ethical,” she said.
She said that western African countries have been very receptive to clinical trials with a placebo control and that the recent Ebola vaccine trial initiated in Liberia, which includes a placebo, has attracted a large number of volunteers.
“We have taken position that the best way forward is an adaptive randomized control trial,” she said. “We think that is the best way to protect patient safety now. We know that new Ebola outbreaks will occur and now is the time to do this right.”
There are other issues to consider, said Nancy Kass, Sc.D., the Phoebe R. Berman Professor of Bioethics and Public Health in the Department of Health Policy and Management at the Johns Hopkins Bloomberg School of Public Health and Director for Public Health at the Berman Institute of Bioethics.
Kass acknowledged that for a vaccine trial, without a placebo control, “how else can we learn that the vaccines work?” But she said for evaluating treatments, there could be other options.
“Ethics is often about thinking of a creative third option,” she said, “and that often requires getting a lot of people with a lot of different expertise in the same room who can think creatively.”
For example, Kass said that one option could be to hold a small pilot study with 40 patients where all get the treatment to see if the experimental treatment is overwhelmingly effective, a “home-run drug.”
“So if out of 40 people, 38 get up and walk away, you don’t need a placebo,” she said. “But if 38 people did not walk out, you actually have a lot more ethical justification for introducing a placebo.”
Next up: The Commission seeks perspective on the Ebola response from veterans of past fights against infectious disease outbreaks.