Research studies and interventions sometimes offer potential benefits to subjects that compensate for the risks they face. Other studies and interventions, which I refer to as “nonbeneficial” research, do not offer subjects a compensating potential for benefit. These studies and interventions have the potential to exploit subjects for the benefit of others, a concern that is especially acute when investigators enroll individuals who are unable to give informed consent. US regulations for research with human subjects attempt to address this concern (...) by mandating strict protections for nonbeneficial research with subjects who cannot consent. Typically, humans who cannot consent, such as children, may be enrolled in nonbeneficial research only when it poses low risks and has the potential to gather information of sufficient value to justify the risks, an appropriate surrogate gives permission on the individual’s behalf and the individual agrees (assents). In contrast, US regulations for nonbeneficial research with nonhuman primates do not include these protections, even though it too involves subjects who cannot consent and who face risks for the benefit of others. Is this difference in regulatory protections justified? Or does the principle of fairness—treat like cases alike—imply that regulations for nonbeneficial research with nonhuman primates should include protections similar to those that apply to nonbeneficial research with humans who cannot consent? (shrink)

One of the key ethical requirements for biomedical research is that it have an acceptable risk-benefit profile (Emanuel, Wendler, and Grady 2000). The International Conference of Harmonization guidelines mandate that clinical trials should be initiated and continued only if “the anticipated benefits justify the risks” (1996). Guidelines from the Council for International Organizations of Medical Sciences state that biomedical research is acceptable only if the “potential benefits and risks are reasonably balanced” (2002). U.S. federal regulations require that the “risks to (...) subjects” be “reasonable in relation to anticipated benefits, if any, to subjects and the importance of the knowledge” to be gained from the .. (shrink)

Research risks have to meet minimal risk requirements in order for the research to qualify for expedited ethics review, to be exempted from ethics review, or to be granted consent waivers. The definition of “minimal risk” in the Common Rule (45 CFR 46) relies on the risks-of-daily-life and risks-of-routine-tests as comparators against which research activities are assessed to meet minimal risk requirements. While either or both comparators have been adopted by major ethics codes, they have also been criticized. In response (...) to criticisms, elaborations, and alternative comparators have been proposed. In this paper, I approach the search for workable comparators from the point of view that ethical reasoning about minimal risk involves analogical reasoning using comparators. In this regard, I develop two necessary conditions for an adequate minimal risk conception, which I use to assess three comparators. I conclude that the risks-of-routine-tests best fits the analogical reasoning operating in minimal risk assessments. (shrink)

Non-beneficial paediatric research is vital to improving paediatric healthcare. Nevertheless, it is also ethically controversial. By definition, subjects of such studies are unable to give consent and they are exposed to risks only for the benefit of others, without obtaining any clinical benefits which could compensate those risks. This raises ethical concern that children participating in non-beneficial research are treated instrumentally; that they are reduced to mere instruments for the benefit of science and society. But this would make the research (...) incompatible with the widely endorsed principle of the primacy of the human subject, which stipulates that the interests of the participating individual should prevail over the interests of science and society. This paper deals with this conflict. It analyses solutions to this problem developed in the literature, and shows that they are unsuccessful. Finally, it offers a new idea of how to reconcile the conduct of non-beneficial paediatric research with the PP. The paper argues for a new formula of the PP, and shows that it implies a specific non-comparative definition of the minimal risk threshold. (shrink)

One of the fundamental ethical concerns about biomedical research is that it frequently exposes participants to risks for the benefit of others. To protect participants’ rights and interests in this context, research regulations and guidelines set out a mix of substantive and procedural requirements for research involving humans. Risk thresholds play an important role in formulating both types of requirements. First, risk thresholds serve to set upper risk limits in certain types of research. Second, risk thresholds serve to demarcate risk (...) categories that streamline risk-adapted systems of ethical oversight. But although risk thresholds play such an important role in research governance, there is a need both to better define the existing risk thresholds and to delineate new thresholds in order to develop more risk-adapted systems of research oversight. The present paper examines the existing minimal risk threshold and the surrounding debates with the goal of deriving a systematic approach to setting thresholds of research risk. (shrink)

Ethical challenges to certain aspects of research on human subjects are not uncommon; examples include challenges to first-in-human trials (Chapman in J Clin Res Bioethics 2(4):1–8, 2011), certain placebo controlled trials (Anderson in J Med Philos 31:65–81, 2006; Anderson and Kimmelman in Kennedy Inst Ethics J 20(1):75–98, 2010) and “sham” surgery (Macklin in N Engl J Med 341:992–996, 1999). To date, however, there are few challenges to research when the subjects are competent and the research is more than minimal risk (...) with no promise of direct benefit. The principal reason given for allowing research that is more than minimal risk without benefit is that we should respect the autonomy of competent subjects. I argue that though the moral intuitions informing respect for autonomy are sound, there is another set of intuitions regarding what we take to be just treatment of another when one agent knowingly causes or allows suffering on another agent. I argue that concerns generated by commutative justice serve as limitations on permissible research. I highlight our intuitions informing this notion of justice by appealing to work done on theodicy; what counts as a morally sufficient reason for God to allow suffering in humans is applicable also to the researcher-subject relationship. I conclude that all human subjects who are exposed to more than minimal risk research should enjoy the same actual protections (e.g., subpart D) as those given subjects who cannot consent. (shrink)

The American Journal of Bioethics, Volume 12, Issue 1, Page 37-38, January 2012.

The concept of minimal risk has been used to regulate and limit participation by adolescents in clinical trials. It can be understood as setting an absolute standard of what risks are considered minimal or it can be interpreted as relative to the actual risks faced by members of the host community for the trial. While commentators have almost universally opposed a relative interpretation of the environmental risks faced by potential adolescent trial participants, we argue that the ethical concerns against the (...) relative standard may not be as convincing as these commentators believe. Our aim is to present the case for a relative standard of environmental risk in order to open a debate on this subject. We conclude by discussing how a relative standard of environmental risk could be defended in the specific case of an HIV vaccine trial among adolescents in South Africa. (shrink)