Earlier this week, the World Health Organization, responding both to the international outcry over the rapidly rising number of Ebola cases and deaths across sub-Saharan Africa (and critiques of the speed of their action), and the news that western health care workers and ministry had found ways to get access to the untested-in-humans Ebola drug ZMapp, convened a panel of ethicists to offer recommendations on more widespread use of experimental Ebola treatments.
The issues considered by the ethicists included:
1) Whether it is ethical to use unregistered interventions with unknown adverse effects for possible treatment or prophylaxis. If it is, what criteria and conditions need to be satisfied before they can be used?
2) If it is ethical to use these unregistered interventions in the circumstances mentioned above, then what criteria should guide the choice of the intervention and who should receive priority for treatment or prevention?
Public health ethicists have raised an array of caution flags about ZMapp’s use in such circumstances, among them: the drug not having been tested in humans, resulting in a lack of data on ZMapp’s safety, efficacy or dosage (which could only be determined through controlled clinical trials); the inability to discern what benefits (or harms) might specifically be attributable to the treatment, given the placement of the American patients into a highly specialized treatment facility in Atlanta; that it is unlikely the drug would have been made available to patients in the U.S. absent approval from the FDA; that one reason the drug was given to these patients was the charity with which they were affiliated sought out the drug from the manufacturer (as opposed to the patients getting some special dispensation from the U.S.); and that because little of the drug is available, and it would take time to ramp up production, it would be impossible to offer access in the near future to the general population. That being said, many of us also argued that it is morally justified to prioritize first responders in an outbreak for treatment when limited medications are available, due to the significant risks to which these care providers voluntarily expose themselves (Caplan, Kass, Silverman), the magnifying effect that offering first responders care can have to extend help in an emergency (Kass, Silverman), and due to implicit agreements western aid organizations make with providers when they take on dangerous assignments (Caplan). (I’ve catalogued many of these discussions in a Storify here).
Earlier today, the World Health Organization’s Ethics panel determined that:
In the particular circumstances of this outbreak, and provided certain conditions are met, the panel reached consensus that it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects, as potential treatment or prevention.
Ethical criteria must guide the provision of such interventions. These include transparency about all aspects of care, informed consent, freedom of choice, confidentiality, respect for the person, preservation of dignity and involvement of the community.
In order to understand the safety and efficacy of these interventions, the group advised that, if and when they are used to treat patients, there is a moral obligation to collect and share all data generated, including from treatments provided for ‘compassionate use’ (access to an unapproved drug outside of a clinical trial).
The WHO panel appears to have settled on more of a bioethics than public health ethics framework for working through the issues. The moral grounds cited are individual patient-centric, rather than population focused, with autonomy at the core. The criteria resonate with the enhanced informed consent approach process used with off-label use of approved drugs. For example, the 2013 revision of the Declaration of Helsinki recommends the following approach to use of unproven treatments in clinical practice:
In the treatment of an individual patient, where proven interventions do not exist or other known interventions have been ineffective, the physician, after seeking expert advice, with informed consent from the patient or a legally authorised representative, may use an unproven intervention if in the physician’s judgement it offers hope of saving life, re-establishing health or alleviating suffering. This intervention should subsequently be made the object of research, designed to evaluate its safety and efficacy. In all cases, new information must be recorded and, where appropriate, made publicly available.
At this point, population-focused ethical considerations (Lisa Lee has compiled an outstanding list of possible frameworks here appear largely to be relegated to three areas:
- transparency (which could mean transparency in disclosing that there are “unknown unknowns” in offering this treatment, or transparency in the policy-making process);
- “involvement of the community,” which could be more of a signal to cultural competence than anything else; and
- data collection and sharing.
To me, probably the most interesting aspect of this news is the role into which the ethicists were placed. The questions posed to the panel by the WHO were written in a way that resonate both with lawyer-client relationships and a “Getting to Yes” framework as might be used in clinical ethics.
While I have no doubt about the ability of the ethicists to weigh all sides of the ethical issues before them, the WHO, as the client, seemed to have in mind an end that it sought – namely, finding a rationale that would justify broader access to experimental drugs. More of a “Yes, if…” request to the panel (or an elephant guiding the rider, to use a Jonathan Haidt metaphor Scott Burris likes) than an open-ended exploration of the moral issues at hand.
The WHO panel recommendation opens the door to increased use of experimental treatments to address the epidemic. However, the ethics committee notes there are still plenty of ethical questions to be addressed, including:
- ethical ways to gather data while striving to provide optimal care under the prevailing circumstances;
- ethical criteria to prioritize the use of unregistered experimental therapies and vaccines;
- ethical criteria for achieving fair distribution in communities and among countries, in the face of a growing number of possible new interventions, none of which is likely to meet demand in the short term.
To be continued…