Epilogue: Ethical Lessons from Ebola Virus Disease

Nulla (enim) res tantum ad dicendum proficit, quantum scriptio.

—Cicero

Nothing so much assists learning as writing down what we wish to remember. Reflecting on Cicero’s words and all of those written in this book, there is much to remember—and much to learn—from the 2013–2016 West African Ebola virus disease (EVD) epidemic. This chapter summarizes the deliberations and recommendations of the Presidential Commission for the Study of Bioethical Issues (Bioethics Commission) as outlined in its February 2015 report, Ethics and Ebola: Public Health Planning and Response. The Bioethics Commission examined the ethical dimensions of the ongoing epidemic and wrote down what it wished for us to remember as we face future public health emergencies. In the report, the Bioethics Commission observed, “The current Ebola epidemic reveals how our engagement in outbreaks of infectious disease can reflect national values. Deliberate development of public health policies in accordance with high ethical and evidentiary standards is the mark of a society committed to national and global health.”1 This sentiment forms the basis of the Bioethics Commission’s seven recommendations for future public health preparedness planning.

The Ethical and Prudential Imperative to Act

Although slow to react during the first half of the Ebola epidemic, international response grew throughout late 2014 and early 2015. Once cases of EVD were diagnosed outside the western African region, governments—including officials in the United States—came to realize that engagement in this global public health emergency served the collective interests of all nations. Stemming the tide of infection at its source, preventing global spread, and stabilizing political and economic systems at risk of collapse from the devastating outbreak represented important pragmatic and self-interested motivations for global action. Engagement based on such enlightened self-interest and recognition that our interests are interconnected and mutually reinforcing have the potential to move us toward a wider worldview that incorporates a moral imperative.

The West ultimately recognized that it had a moral imperative, based in our common humanity, to provide assistance in the face of abject suffering. Both the public and those in a professional position to respond recognized the great need for engagement. Whether based in social justice and the obligation to respond to the health needs of the severely disadvantaged, or in the tacit expectations resulting from former colonial relationships, the ethical justification for intervention was clear.

In the end, the West’s response revealed both its ethical and prudential interests in fighting Ebola, even if half a world away. In its first recommendation, the Bioethics Commission concluded, “In an interconnected world, for ethical reasons and to protect national interests, the US government has a responsibility to engage in preparedness and to participate in coordinated global responses to public health emergencies.”2

Further noting that an effective public health response to future emergencies requires coordinated public health infrastructure and international response capacity, the Bioethics Commission’s second recommendation was to strengthen key elements of the United States’s global response capabilities. Specific measures cited for improvement included strengthening the World Health Organization through increased funding and collaboration with other governmental and nongovernmental responders; empowering a single US health official to serve as the responsible party for all federal response to domestic and international public health emergencies; and strengthening the deployment capability of the US Public Health Service, which serves as the US point organization for public health emergency response.3

In the face of a public health emergency, public support for domestic policy and global engagement requires transparency and accountability. Engaging the public through clear communication of scientifically sound information—as well as recognizing and acknowledging existing uncertainties—fosters trust and support for action in response to public health emergencies. In chapter 8 of this volume, Kim Yi Dionne and Laura Seay describe the multiple misconceptions held by the American public during the 2013–2016 EVD epidemic.4 As they report, misperceptions about geography and history can have devastating effects in a global public health emergency.

Clear information about how population health during an outbreak differs from individual clinical care, for example, can assist the public with understanding the need for movement restrictions and other effective public health interventions such as contact tracing. Evidence-based policies that reduce—or at least do not exacerbate—existing inequities are critical. In addition, policies based on the least possible infringement of personal liberty are ethically preferable. If choosing between policy options, all else being equal, the one with the least intrusion on individual freedom is the most defensible choice.

Preparation for public health emergencies includes not only planning logistics and ensuring necessary supplies, but also preparing the public. Proactive deliberation and education before emergencies can assist public officials with addressing conflicting values that can complicate policy making in our diverse society. Deliberative decision making requires time. It involves exploration of a plurality of views, reflection, and respectful exchange of ideas. Engaging in deliberative processes as a part of public health preparedness is best begun during non-emergent times. Inevitably, public engagement is necessary during emergencies as well, and public health should put these systems in place during nonemergency deliberations for use during or in the aftermath of crises.

Effective communication is directly connected to successful uptake of public health policies, and the Bioethics Commission recommended that public health professionals educate the public and communicate clearly about the nature and justification of public health responses. Communication efforts should provide the public with accurate information about the response, including what is known and what is not known. Efforts also must provide persons most directly affected by public health response policies with the reasoning behind them, as well as the values reflected in policy implementation. Across all communication efforts, the Bioethics Commission urged approaches and techniques that mitigate stigmatization and discrimination that can result during public health emergencies.5

One of the most poignant lessons from this Ebola outbreak was the need for real-time integration of ethical decision making to complement response planning. The Bioethics Commission noted that during public health emergencies, public health professionals and policymakers need responsive and accessible resources to assist them with the myriad ethical challenges that inevitably arise in the course of the response. Patricia Henwood remarks on the need for “real-time evolution” of EVD management in chapter 2.6 Integration of ethics into this real-time evolution is essential in order to facilitate questions of what we should do that are raised by emerging questions of what we can do. These ethical problem-solving resources work best when they are integrated into the established public health infrastructure. While calling in a consulting ethicist when something troubling arises in the midst of a crisis can be helpful, policy decisions that incorporate ethical considerations during the planning process can help public health professionals anticipate, identify, and address ethical concerns throughout policy development and implementation. Including ethical expertise in response monitoring and post-response evaluations also can assist with preparation for future emergencies.

To ensure that ethical principles are incorporated into timely and agile public health emergency response, the Bioethics Commission recommended, “Qualified public health ethics expertise should be readily available to identify ethical considerations relevant to public health emergencies and responses in light of real-time available evidence.”7 To realize ethics integration as more than an add-on from outside the public health infrastructure, the commission recommended that a single US public health official be accountable for all domestic and international emergency response, including integrating ethics as an essential part of the response.8

Public Health Practice and Research during Emergencies

In the 2013–2016 EVD epidemic, several US public health actions required thorough ethical consideration. The lack of ethics engagement in planning for such an emergency led to real-time examination of three especially challenging issues: quarantine, the use of placebo-controlled trials, and the collection and sharing of biospecimens.

Quarantine

From a public health practice perspective, requiring and enforcing movement restrictions during an infectious disease outbreak raises a number of ethical considerations, many of which are outlined by Kelly Hills in chapter 16.9 Most of these challenges revolve around the tension between the individual liberty we have come to expect in liberal democracies and the communal orientation of public health interventions needed to contain the spread of disease. Limiting one’s ability to move about and interact freely is a severe intervention and ought be applied only when nothing less will serve the same end. This claim is based on the principle of least infringement, which requires public health officials to implement the least intrusive approach to achieve the public health goal. What measures achieve the public health goal depend on characteristics of the infectious agent as well as willingness of affected communities to participate. Agent characteristics include mode and ease of transmission, the infectious period, severity of resulting illness, availability of treatment, and associated mortality, among others. Community willingness to abide by public health movement restrictions depends on a clear understanding of and justification for such measures. Affected communities must be assured that the policy is evidence-based, represents the least possible infringement on individual liberty for the shortest duration, and is implemented justly and equitably.

The Bioethics Commission examined lessons from past epidemics such as SARS, tuberculosis, and HIV. During the 2002–2003 SARS epidemic, countries across the globe experienced various levels of cooperation with quarantine and isolation orders. Success was correlated with vigorous public education and financial subsidies for missed wages and other expenses for persons quarantined. Tuberculosis, like SARS, is spread via respiratory droplets expelled when an infectious persons sneezes or coughs. Public health laws in US states give public health officials authority to quarantine and isolate infectious persons, but these restrictive orders are enforced only after less intrusive measures, such as directly observed therapy, fail. HIV, unlike SARS and tuberculosis, is relatively difficult to transmit; it requires contact with infected blood, semen, or vaginal fluid. Still, for the first few decades of the epidemic, fear drove much of the public response and many policy decisions. The need for accurate communication of evidence-based information remains in the fight against HIV and other infectious pathogens. A lesson common to all of these examples is the need to anticipate and mitigate public fear. When an infectious threat creates fear—real or imagined—communities often marginalize and stigmatize persons whom they perceive to be a threat. This “othering” often has severe social consequences ranging from discrimination to property damage to physical harm or death in egregious cases, as Kim Yi Dionne and Laura Seay discuss in chapter 8. Unfortunately, these consequences still occur. In the 2013–2016 EVD epidemic, Liberian-Americans and other members of the African diaspora reported experiencing overt hostility from strangers. Health care workers returning from volunteering in western Africa faced discrimination themselves and worried that their families would suffer consequences by association. These experiences give us an opportunity to consider carefully what ethical dimensions must be addressed when considering movement restrictions.

The Bioethics Commission outlined five ethical principles or conditions that provide justification for movement restrictions in the face of a public health emergency. The first two, the harm principle and the principle of least infringement, address the importance of minimizing the impingement on individual liberty. The harm principle guides us to limit the restrictions on individual liberty to those necessary to keep an individual or group from harming others. The principle of least infringement supports the imposition of the least intrusive effective public health interventions; if another intervention is as effective, but intrudes less on liberty, it should be used in place of the more intrusive one. The third principle, beneficence, along with its corollary, nonmaleficence, guides us to consider interventions that promote benefit while not introducing harm. Movement restriction in the context of an infectious disease epidemic can promote great benefit, but is not without harms. In this case, a related concept, proportionality, requires that the probable benefit of the intervention is sufficient to justify its burden. The fourth principle, reciprocity, compels us to consider necessary support for persons who bear the burden of interventions that protect the public’s health. Examples of reciprocal support include access to goods such as food and clothing, compensation for lost income, and protection and care for dependents. Specific types and amount of support are determined by context and depend, in part, on the size of the affected population. Finally, the commission included justice and fairness as an essential ethical consideration for movement restriction. This principle requires that the benefits and burdens of public health response be distributed equitably and not exacerbate existing disparities. For example, discriminatory practices such as imposing restrictions on whole subsets of the population without evidence-based justification are unjust.

These principles are reflected in the Bioethics Commission’s fifth recommendation, which states, “Governments and public health organizations should employ the least restrictive means necessary—on the basis of the best available scientific evidence—in implementing restrictive public health measures, such as quarantines and travel restrictions.”10 The commission concludes this recommendation stating that public health officials have an ethical duty to clearly communicate the rationale for restrictive measures, especially to persons most affected by them, and to update related requirements as evidence develops.

Public Health Research

The conduct of public health and clinical research during an emergency raises numerous ethical questions. Whether research should be done at all when care needs are high is less controversial than exactly how such research ought to be conducted. Annette Rid describes some of the ethical debate associated with conducting research during the 2013–2016 epidemic in chapter 14.11

In its ethical analysis the Bioethics Commission recognized an ethical obligation to learn what we can in the presence of a public health emergency in order to provide the best possible management of the situation, and—importantly—to prepare for the next emergency. There are numerous challenges to conducting research ethically in the midst of a public health emergency, including incorporating rapidly changing information; ensuring resources are used to attend to urgent health and safety needs; and ensuring just and equitable distribution of benefits. Research can only go forward on a foundation of public trust. This trust must be built during non-emergency times and maintained in the midst of a crisis. Morenike Oluwatoyin Folayan and Bridget Haire describe the importance of community trust in chapter 15.12 Proactive public deliberation and transparency are keys to coping with communities in great need. Building capacity for public engagement of affected persons and their families, communities, and leaders is as essential as conducing first-rate science.

Placebo-Controlled Trials

One of the two predominant research ethics-related issues raised during the early months of the 2013–2016 Ebola epidemic was the use of placebos in clinical testing of pharmaceutical treatments and vaccine candidates. With no known treatment and no effective vaccine in the face of a lethal virus, trials to develop these were sorely needed. The placebo-controlled trial is the most scientifically rigorous way to show effectiveness of a drug candidate, producing results with the fewest participants in the shortest time compared with other methods. However, such trials require that some participants be randomly assigned to receive a “sugar pill” or inactive dose of the trial medication. This produces an ethical tension between speed of discovery and the reality that, in public health emergencies involving such high mortality rates, all persons want access to medicines with even a remote possibility of helping.

Researchers have been debating the ethics of the use of placebos in clinical trials for many years. Withholding treatment to test the safety and efficacy of a new intervention is ethically complex. However, in a situation like the Ebola epidemic where there are no approved treatments, the ethical argument is not whether to withhold existing treatment, but rather whether or not all patients should be given a treatment that has the possibility of benefit, even if the benefit is unproven and the treatment could cause harm. Requiring the best possible research design, given the constraints and the context, is morally required. The Bioethics Commission has held that ethical science begins with quality science.13 Undertaking flawed science lacks social value and puts participants at risk while yielding no possibility of societal benefit.

The Bioethics Commission considered four ethically relevant considerations for examining the ethical challenges involved in choosing a research design that provides the best possible evidence in the shortest period (i.e., a placebo-controlled trial) and other designs that would provide all participants with potential benefit but might take longer, require more participants, or possibly compromise interpretation of results. First, there are important scientific and ethical differences between vaccine trials and treatment trials. In vaccine trials, participants are healthy volunteers and are not likely to directly benefit from participation. In vaccine trials, it is ethically preferable to include as few healthy volunteers as possible to achieve accurate scientific results—again, through the placebo-controlled trial.

Second, when considering a disease like Ebola, where mortality is high and there are no known treatments, treatment trials by definition include persons who are ill and in need of supportive care. In a placebo-controlled trial design, participants should receive the best available supportive care. The definition of “best available supportive care” must be addressed. Does it mean the best possible care available anywhere? The best possible care given the circumstances? The level and type of care that is sustainable in the local context once the research is complete? Providing sustainable supportive care is most prudent for numerous reasons, two of which include longer-term sustainability once international aid retreats and ensuring that superior supportive care in a treatment trial does not mask results of an effective treatment.

Third, the Bioethics Commission considered the important role of community responsiveness in designing effective trials. Affected persons must be willing to participate in clinical trials, which makes it critical to engage communities about what is palatable with respect to research design. The best trial design is rendered useless if communities are unwilling to participate in the study.

Lastly, considering their contention that ethical science begins with good science, the Bioethics Commission considered that while differences remain between persons advocating for placebo-controlled trials and those arguing for alternative designs, the primary concern is that the trial design yield credible results. Risks to participants cannot be justified if trial design does not allow for benefit to be realized.

Consideration of these factors led the Bioethics Commission to its sixth recommendation stating that research should be designed to ensure that all participants receive the best supportive care that is sustainably available in the host community. Researchers should implement methodologically rigorous designs that produce clearly interpretable results and are acceptable to the host community. Carefully designed placebo-controlled trials can meet these demands; where they cannot, innovative designs such as adaptive randomized trials should be considered. Research teams should engage with affected communities to determine what trial design best meets the extant ethical and scientific requirements.14

Collection and Future Use of Biospecimens

Another research-related concern that garnered attention during this Ebola epidemic was the ethical collection and future use of biospecimens for research. Like the placebo issue, the collection and future use of biospecimens is not unique to the Ebola epidemic. The literature on this topic is robust, and the Bioethics Commission first addressed it in their report, Privacy and Progress in Whole Genome Sequencing.15 Familiar ethical considerations like privacy and consent exist in the public health emergency context as well, but there are additional ethical complexities to which researchers must attend in an infectious disease outbreak and potential pandemic in low- and middle-income countries. One of these concerns equitable benefit sharing. Animated by reciprocity and justice, persons and communities that provide samples must not be denied access to the benefits derived from them. This concern is especially important when the specimens must be transported to high-resource laboratories equipped to perform research with dangerous pathogens, which generally exist in more developed countries. Allowing specimens to be collected and used for research requires trust that the benefits will be available to the communities that supplied the biospecimens, even if that community cannot afford to purchase them at market value. As the opportunity to acquire specimens might arise only during a public health emergency, researchers and policymakers would benefit from engaging with global partners in planning for biospecimen collection.

In the last recommendation in Ethics and Ebola, the Bioethics Commission called on the US government and global partners to ensure that biospecimens are obtained ethically and to facilitate access to the resulting benefits to the broadest group possible. They recommended that global partners “work collaboratively with local scientists whenever possible to develop effective strategies for ensuring equitable distribution of the benefits of research.”16

Conclusion

While not officially declared over, as of September 2015 the epidemic had waned considerably, and Sierra Leone, Guinea, and Liberia had begun to rebuild. Schools were back in session after closure for nearly an entire academic year; care once again was available from antenatal clinics, which were closed to accommodate Ebola patients and to avoid spreading the disease. Before the lens of history colors our memory, we are right to ensure that the lessons of the largest, most widespread Ebola virus epidemic in history guide our public health planning and response. It is clear that a swift, evidence-based response to public health emergencies is ethically required and prudentially justified. Our public health preparedness includes ethical preparedness, and we are wise to ensure early and explicit infusion of ethical considerations and problem solving into our public health emergency response.

Disclaimer

The content of this manuscript represents the opinions and conclusions of the author and does not necessarily represent those of the US Presidential Commission for the Study of Bioethical Issues or the US Department of Health and Human Services.