The Ebola virus disease outbreak in West Africa that has so far claimed the lives of more than 2,900 people captured the worlds attention. The steady rise in the death count and efforts to thwart Ebolas spread remain top stories in the news. But when two American healthcare workers contracted the virus and were given ZMapp, an experimental drug that was previously untested in humans, the ethical considerations behind the use of experimental drugs in extreme cases of illness was thrust into the forefront.
The scientific process of testing a new drug starts with the process of concept and design, followed by test tube (or bench) studies and then by animal studies (preclinical stage). Data analysis from successful animal studies is required to support safety for clinical drug trials in humans. In the case of ZMapp, the drug had not gone through clinical trials so its safety and effectiveness had not been tested in humans yet it still was given to Kent Brantly, MD, and Nancy Writebol, the American healthcare workers who contracted Ebola in Monrovia, Liberia. The move raised ethical concerns in administering ZMapp for treatment, not research, that included:
the high potential for harm by doing nothing
the high potential for harm without safety data on the drug
the informed consent process
the selection of recipients
Because ZMapp is in the preclinical research stage, this is not a compassionate use case. Compassionate use (also called expanded use) refers to the Food and Drug Administrations approved use of an investigational drug (not an untested drug like this one) to treat a patient, especially when research in humans shows promising results and when no comparable or satisfactory alternative treatment options are available. In this outbreak, with the potential for global spread, we are in uncharted territory, where the line between the research world and the clinical care world is blurred.
A key concern with ZMapp was whether the intent of administering the experimental drug was for research or to save lives. In this case, ZMapp was administered with the intent of treating the patients and saving their lives. Not much is known about how ZMapp works in humans, what adverse effects might occur, how this drug affects people with additional health problems and what long-term problems might occur. The potential harms are significant but many people are infected and dying of Ebola as the outbreak spreads. In the face of a high fatality rate, the potential benefit to the recipient must greatly outweigh the potential harm of the drug and the harm of doing nothing when there are no safety assurances or standard therapy.
Informed consentSarah B. Vittone, RN
The selection of the first humans to use ZMapp is a key concern. While impartial and just processes must be in place to initially choose candidates for the drug, the first humans receiving an unstudied drug must be allowed to participate fully in the decision.
Unlike massive inoculations during a public health threat in which the public good is protected by a vaccine that has been proven safe, this untested treatment was not.
Normally, an Institutional Review Board providing human studies protections would have reviewed the consent statements, but in the state of this emergency, this also could be done without prior approval. How Brantly and Writebol were presented with information about the experimental drug in their vulnerable condition, before signing the consent forms, is important to the process. Did they have advocates with them? Did they understand the information? Could they apply sound reasoning and appreciate the impact of receiving the drug?
Perhaps the rationale to allow Brantly and Writebol to be the first human recipients of ZMapp was because they have some knowledge of the research nature of the treatment and worked with Ebola patients; their awareness of Western medicine and the spread of disease; and their ability to participate in the decision. It is likely their level of understanding would have satisfactorily met this level of informed consent.
There must be a clear process for advocacy and safety with respect for dignity and impartiality when considering using untested experimental drugs in the general population. Cultural and other differences to understanding the implications of these drugs must be taken into account.
Future implications and considerations
How the Ebola outbreak will be curtailed is yet to be established. Ethical processes for the just use of resources for containment are of key importance. The current limited supply of ZMapp and other experimental drugs in the pipeline reveal the unfortunate lack of local and global preparedness for this outbreak. The lack of established treatment, want of protective supplies (gloves and masks) and withdrawal of healthcare workers, according to media reports, can lead to unchecked illness in the absence of sustainable healthcare. Ebola continues to present a high physical threat to healthcare workers unable to effectively treat their patients or to protect themselves.
The use of resources at both a local and global level must respect and protect human dignity and the right to basic healthcare. Prevention and protection also is foundationally a communication issue. How quickly and effectively local healthcare workers communicate about suspected outbreaks and how government and global health infrastructure responds is key to health safety.
The Americans treated with ZMapp have been discharged from the hospital and are doing well. Research is ramping up to provide the safety data on using ZMapp and other options for Ebola treatment, and we should continue to consider our ethical obligations as this outbreak, or others like it, shows the potential to spread to the U.S.
As Susan M. Grant, MS, RN, CNAA, BC, CNO for Emory Healthcare and interim dean for Nell Hodgson Woodruff School of Nursing, said in an Aug. 6 Washington Post article, The insight we gain by caring for them will prepare us to better treat emergent diseases that may confront the U.S. in the future. We also can export our new knowledge to treat Ebola globally Today, diseases do not stay contained to one city, country or even continent.
Nursings role in these global ethical conversations will be key to advocacy and protections for the global community, the ill and healthcare workers.