The role of community engagement in addressing bystander risks in research: The case of a Zika virus controlled human infection study

There is limited guidance on how to assess the ethical acceptability of research risks that extend beyond research participants to third parties (or “research bystanders”). Community or stakeholder engagement has been proposed as one way to address potential harms to community members, including bystanders. Despite widespread agreement on the importance of community engagement in biomedical research, this umbrella term includes many different goals and approaches, agreement on which is ethically required or recommended for a particular context. We analyse the case of a potential Zika virus human challenge trial to assess whether and how community engagement can help promote the ethical acceptability of research posing risks to bystanders. We conclude that, in addition to having intrinsic value, community engagement can improve the identification of bystander risks, effective approaches to minimizing them, and transparency about bystander risks for host communities.     

Bystanders and ethical review of research: Proceed with caution

Scientists seeking to conduct research with human subjects must first submit their proposals to research ethics committees (Institutional Review Boards [IRBs], in the United States). Some of these studies pose risks to “bystanders,” i.e., people who may be affected by the research but who are not enrolled as study subjects. Should IRBs expand their scope to include oversight over possible harms to bystanders as well as research subjects? This paper presents arguments against this step. Prior review of research with human subjects, despite its evident burden on the research enterprise, is a necessary caution, because the tension between the objectives of humane treatment of research subjects and sound scientific design and procedure has in the past led to serious abuses. This rationale is inapplicable in the case of bystanders. Moreover, in view of the many and varied effects of both research practices and scientific advances on the broader public over time, those who may be considered to be “bystanders” may potentially expand without limit; requiring IRBs to anticipate these distant and long-term effects as part of prior ethical review could greatly increase its burden and its deterrent effect on research. While conducting research without concern for serious potential harm to bystanders may be irresponsible and unethical, expanding the scope of prior review by IRBs to include risks to bystanders is not required by the principles governing human subjects research, and the costs and burdens of this expansion may outweigh any expected gains.     

Study bystanders and ethical treatment of study participants—A proof of concept

The ethics of research on human subjects is often construed as a fine balance between the interests of patients in need of novel health interventions, and those of study participants who should remain safe in the process. But there is a third group in the mix. Some people belong to neither category, yet research can affect or jeopardize them. Call such people “bystanders.” This article shows that thinking about bystander protection can question whether there is an upper limit on the risks that studies may legitimately visit upon their participants. Thus, thinking about appropriate bystander protection can shed light on the appropriate protection of study participants. Core research ethics, which focuses on the latter, must consider the former as well.     

Risky research and bystander consent

There is no quick and easy answer to the question whether research activities that endanger bystanders without their consent ever thereby violate those bystanders’ rights. We cannot dismiss the idea that bystanders possess strong rights against researchers simply on the grounds that they are, after all, merely bystanders. Indeed, it is easy to imagine scenarios in which researchers would be morally required to gain the informed consent of bystanders whom they risk harming. Whether bystander consent is required in any particular real-world case will depend, in part, upon exactly how the research activity endangers them.     

Social eavesdropping and the evolution of conditional cooperation and cheating strategies

The response of bystanders to information available in their social environment can have a potent influence on the evolution of cooperation and signalling systems. In the presence of bystanders, individuals might be able to increase their payoff by exaggerating signals beyond their means (cheating) or investing to help others despite considerable costs. In doing so, animals can accrue immediate benefits by manipulating (or helping) individuals with whom they are currently interacting and delayed benefits by convincing bystanders that they are more fit or cooperative than perhaps is warranted. In this paper, I provide some illustrative examples of how bystanders could apply added positive selection pressure on both cooperative behaviour and dishonest signalling during courtship or conflict. I also discuss how the presence of bystanders might select for greater flexibility in behavioural strategies (e.g. conditional or condition dependence), which could maintain dishonesty at evolutionarily stable frequencies under some ecological conditions. By recognizing bystanders as a significant selection pressure, we might gain a more realistic approximation of what drives signalling and/or interaction dynamics in social animals.     

VULNERABILITY IN RESEARCH AND HEALTH CARE; DESCRIBING THE ELEPHANT IN THE ROOM?

Despite broad agreement that the vulnerable have a claim to special protection, defining vulnerable persons or populations has proved more difficult than we would like. This is a theoretical as well as a practical problem, as it hinders both convincing justifications for this claim and the practical application of required protections. In this paper, I review consent-based, harm-based, and comprehensive definitions of vulnerability in healthcare and research with human subjects. Although current definitions are subject to critique, their underlying assumptions may be complementary. I propose that we should define vulnerability in research and healthcare as an identifiably increased likelihood of incurring additional or greater wrong. In order to identify the vulnerable, as well as the type of protection that they need, this definition requires that we start from the sorts of wrongs likely to occur and from identifiable increments in the likelihood, or to the likely degree, that these wrongs will occur. It is limited but appropriately so, as it only applies to special protection, not to any protection to which we have a valid claim. Using this definition would clarify that the normative force of claims for special protection does not rest with vulnerability itself, but with pre-existing claims when these are more likely to be denied. Such a clarification could help those who carry responsibility for the protection of vulnerable populations, such as Institutional Review Boards, to define the sort of protection required in a more targeted and effective manner.     

Bystanders,risks, and consent

This paper considers the moral status of bystanders affected by medical research trials. Recent proposals advocate a very low threshold of permissible risk imposition upon bystanders that is insensitive to the prospective benefits of the trial, in part because we typically lack bystanders' consent. I argue that the correct threshold of permissible risk will be sensitive to the prospective gains of the trial. I further argue that one does not always need a person's consent to expose her to significant risks of even serious harm for the sake of others. That we typically need the consent of participants is explained by the fact that trials risk harmfully using participants, which is very hard to justify without consent. Bystanders, in contrast, are harmed as a side-effect, which is easier to justify. I then consider whether the degree of risk that a trial may impose on a bystander is sensitive to whether she is a prospective beneficiary of that trial.     

Using,risking, and consent: Why risking harm to bystanders is morally different from risking harm to research subjects

Subjects in studies on humans are used as a means of conducting the research and achieving whatever good would justify putting them at risk. Accordingly, consent must normally be obtained before subjects are exposed to any substantial risks to their welfare. Bystanders are also often put at risk, but they are not used as a means. Accordingly—or so I argue—consent is more often unnecessary before bystanders are exposed to similar substantial risks to their welfare.     

Cluster randomization and political philosophy

In this paper, I will argue that, while the ethical issues raised by cluster randomization can be challenging, they are not new. My thesis divides neatly into two parts. In the first, easier part I argue that many of the ethical challenges posed by cluster randomized human subjects research are clearly present in other types of human subjects research, and so are not novel. In the second, more difficult part I discuss the thorniest ethical challenge for cluster randomized research--cases where consent is genuinely impractical to obtain. I argue that once again these cases require no new analytic insight; instead, we should look to political philosophy for guidance. In other words, the most serious ethical problem that arises in cluster randomized research also arises in political philosophy.     

Compensation and reparations for victims and bystanders of the U.S. Public Health Service research studies in Tuskegee and Guatemala: Who do we owe what?

Using the infamous research studies in Tuskegee and Guatemala, the article examines the difference between victims and bystanders. The victims can include families, sexual partners, and children not just the participants. There are also the bystanders in the populations who are affected, even vaguely, decades after the initial studies took place. Differing reparations for victims and bystanders through lawsuits and historical acknowledgments has to be part of broader discussions of historical justice, and the weighing of the impact of racism and imperial research endeavors.     

Animal Research Ethics in Africa: Is Tanzania Making Progress?

The significance of animals in research cannot be over‐emphasized. The use of animals for research and training in research centres, hospitals and schools is progressively increasing. Advances in biotechnology to improve animal productivity require animal research. Drugs being developed and new interventions or therapies being invented for cure and palliation of all sorts of animal diseases and conditions need to be tested in animals for their safety and efficacy at some stages of their development. Drugs and interventions for human use pass through a similar development process and must be tested pre‐clinically in laboratory animals before clinical trials in humans can be conducted. Therefore, animals are important players in research processes which directly and indirectly benefit animals and humans. However, questions remain as to whether these uses of animals consider the best interests of animals themselves. Various research and training institutions in Tanzania have established some guidelines on animal use, including establishing animal ethics committees. However, most institutions have not established oversight committees. In institutions where there may be guidelines and policies, there are no responsible committees or units to directly oversee if and how these guidelines and policies are enforced; thus, implementation becomes difficult or impossible. This paper endeavours to raise some issues associated with the responsible use of animals in research and training in Tanzania and highlights suggestions for improvement of deficiencies that exist in order to bridge the gap between what ought to be practised and what is practised.     

Coherent use of information by hens observing their former dominant defeating or being defeated by a stranger

This study examines the role of observation during the formation of triads in female domestic hens. Results indicate that during hierarchy formation, a hen observing agonistic interactions and conflict settlement between its former dominant and a stranger uses this information when in turn confronted by the latter. Under a first condition (E, n = 15 triads), bystanders witnessed their prior dominant being defeated by a stranger before being introduced to them. In a second condition (C1, n = 16 triads), bystanders witnessed the victory of their prior dominant over a stranger. In a third condition (C2, n = 15 triads), bystanders witnessed two strangers establishing a dominance relationship before being introduced to their prior dominant and to a stranger the former had just defeated. The behavioural strategies of bystanders depended on the issue of the conflict they had witnessed. Bystanders of the E condition behaved as having no chance of defeating the stranger. They never initiated an attack against it, and upon being attacked, readily submitted in turn to the stranger. On the contrary, bystanders of the C1 condition behaved as having some chances against the stranger. They initiated attacks in 50% of cases, and won 50% of conflicts against the stranger. Under condition C2, bystanders first initiated contact with the strangers in only 27% of cases, which approximates the average of their chances for defeating the stranger. However, bystanders finally defeated the strangers in 40% of cases. These results suggest that bystanders of conditions E and C1 gained some information on the relationship existing between their prior dominant and the stranger and that they used it coherently, perhaps through transitive inference, thus contributing to the existence of transitive relationships within the triads. Alternate explanations are examined.     

Ethical Concerns Over Testing on Human Subjects

A Joint Subcommittee of the Scientific Advisory Board and the FIFRA Scientific Advisory Panel recently issued a report to the U.S. Environmental Protection Agency (USEPA) concerning the use of data derived from testing on human subjects. The authors address both scientific and ethical issues pertaining to such research and conclude that as long as certain conditions are met, the deliberate exposure of voluntary subjects to potentially dangerous levels of pesticides can be both scientifically and ethically sound. I argue that there are further ethical problems not adequately addressed in the report. In particular, there are serious concerns about fairness and exploitation in connection with paid volunteers, which also raise questions about the degree to which the conditions of non-coercion and informed consent are likely to be met. The primary aim of this paper is to bring these issues more fully into the discussion. I also consider briefly the constraints placed on legitimate justifications of human studies by the requirement that the promotion of public safety be the ultimate purpose of the studies. This will help to clarify which reasons in support of human studies are in principle legitimate, which will in turn better enable us to weigh them against the ethical concerns about fairness and exploitation.     

Identifying and evaluating layers of vulnerability – a way forward

“Vulnerability” is a key concept for research ethics and public health ethics. This term can be discussed from either a conceptual or a practical perspective. I previously proposed the metaphor of layers to understand how this concept functions from the conceptual perspective in human research. In this paper I will clarify how my analysis includes other definitions of vulnerability. Then, I will take the practical‐ethical perspective, rejecting the usefulness of taxonomies to analyze vulnerabilities. My proposal specifies two steps and provides a procedural guide to help rank layers. I introduce the notion of cascade vulnerability and outline the dispositional nature of layers of vulnerability to underscore the importance of identifying their stimulus condition. In addition, I identify three kinds of obligations and some strategies to implement them. This strategy outlines the normative force of harmful layers of vulnerability. It offers concrete guidance. It contributes substantial content to the practical sphere but it does not simplify or idealize research subjects, research context or public health challenges.     

A moderate Buddhist animal research ethics

Though there is a burgeoning interest in applied Buddhist ethics, Buddhist animal research ethics remains an underdeveloped area. In this paper I will explore how some central Buddhist ethical considerations can usefully engage our use of other animals (henceforth, animals) in science. As the scientific use of animals is broad, I will narrow my focus to laboratory science. I will show that, though a Buddhist abolitionism would not be unmotivated, it is possible to reject it. While doing so, it will be important to resist emphasizing elements of Buddhist thought that merely provide reasons to adopt the dominant ethical framework governing laboratory animal research ethics, known as the 3Rs. Though I will suggest how a Buddhist animal research ethics can sometimes permit the use of animals in harmful research, it will also require ethical constraints that resonate with some of the more progressive elements in ‘Western’ bioethics.     

ON THE NEED FOR IMPROVED PROTECTIONS OF INCAPACITATED AND NON‐BENEFITING RESEARCH SUBJECTS

In this article, it is claimed that the protective provisions for adults with impaired decision‐making capacity are misguided, insofar as they do not conclusively state whether research on this group should be permitted only as an exception, and as they arbitrarily allow for some groups to benefit from such research while others will not. Moreover, the presumed or former will of the subject is given insufficient weight, and the minimal risk standard does not make sense in this context. Because of these problems, the present guidelines allow for the possibility of vulnerable people being exploited, something that is hidden behind a guise of solidarity. Instead we need to address the real issues at stake by rewriting the present statutes. It is suggested that new guidelines should be in some continuity with earlier efforts. However, in order to protect these subjects there is additional need for appointed representatives who monitor research and for legal obligations to compensate for any injuries suffered. Without these or similar measures we won't have an adequate system in place for the protection of non‐benefiting persons who are unable to consent to research.     

Ethical Issues in Adolescents' Sexual and Reproductive Health Research in Nigeria

There is increasing interest in the need to address the ethical dilemmas related to the engagement of adolescents in sexual and reproductive health (SRH) research. Research projects, including those that address issues related to STIs and HIV, adverse pregnancy outcomes, violence, and mental health, must be designed and implemented to address the needs of adolescents. Decisions on when an individual has adequate capacity to give consent for research most commonly use age as a surrogate rather than directly assessing capacity to understand the issues and make an informed decision on whether to participate in research or not. There is a perception that adolescents participating in research are more likely to be coerced and may therefore not fully comprehend the risk they may be taking when engaging in research. This paper examines the various ethical issues that may impact stakeholders' decision making when considering engaging adolescents in SRH research in Nigeria. It makes a case for lowering the age of consent for adolescents. While some experts believe it is possible to extrapolate relevant information from adult research, studies on ethical aspects of adolescents' participation in research are still needed, especially in the field of sexual and reproductive health where there are often differences in knowledge, attitudes and practices compared to adults. The particular challenges of applying the fundamental principles of research ethics to adolescent research, especially research about sex and sexuality, will only become clear if more studies are conducted.     

Professional Hubris and its Consequences: Why Organizations of Health‐Care Professions Should Not Adopt Ethically Controversial Positions

In this article, I argue that professional healthcare organizations such as the AMA and ANA ought not to take controversial stances on professional ethics. I address the best putative arguments in favor of taking such stances, and argue that none are convincing. I then argue that the sort of stance‐taking at issue has pernicious consequences: it stands to curb critical thought in social, political, and legal debates, increase moral distress among clinicians, and alienate clinicians from their professional societies. Thus, because there are no good arguments in favor of stance‐taking and at least some risks in doing so, professional organizations should refrain from adopting the sort of ethically controversial positions at issue.     

Should human germ line editing be allowed? Some suggestions on the basis of the existing regulatory framework

The application of genetic editing techniques for the prevention or cure of disease is a highly promising tool for the future of humanity. However, its implementation contains a number of ethical and legal challenges that should not be underestimated. On this basis, some sectors have already asked for a veto on any intervention that modifies the human germ line, while supporting somatic line editing. In this paper, I will support that this suggestion makes no sense at all, because the somatic/germ line disjunctive has no moral relevance and, therefore, it should not play any role in legal terms. I will provide a number of reasons to hold this assumption, such as the non‐sacred nature of the germ line, the difference between germ line and human genome modification, or the moral importance of the presence of a will to create modified descendants. While doing so, I will provide some examples of the different approaches to germ line editing adopted by different regulations so as to demonstrate that, contrary to what is sometimes stated, a general ban on this practice is not the rule, but the exception. Additionally, I will show how alternative options which currently exist, such as a selective ban based on criteria different to the germ line/somatic line distinction, match better with the need to conciliate research needs and legitimate ethical concerns. Finally, I will introduce some further suggestions to this same purpose.