The inclusion of children in research gives rise to a difficult ethical question: What justifies children's research participation and exposure to research risks when they cannot provide informed consent? This question arises out of the tension between the moral requirement to obtain a subject's informed consent for research participation, on the one hand, and the limited capacity of most children to provide informed consent, on the other. Most agree that children's participation in clinical research can be justified. But the ethical (...) justification for exposing children to research risks in the absence of consent remains unclear. One prevalent group of arguments aims to justify children's risk exposure by appealing to the concept of benefit. I call these ‘benefit arguments’. Prominent versions of this argument defend the idea that broadening our understanding of the notion of benefit to include non-medical benefits helps to justify children's research participation. I argue that existing benefit arguments are not persuasive and raise problems with the strategy of appealing to broader notions of benefit to justify children's exposure to research risk. (shrink)

This thesis is a contribution to the ethical justification for clinical research with children. A research subject’s participation in a trial is usually justified, in part, by informed consent. Informed consent helps to uphold the moral principle of respect for persons. But children’s limited ability to make informed choices gives rise to a problem. It is unclear what, if anything, justifies their participation in research. Some research ethicists propose to resolve this problem by appealing to social utility, proxy consent, arguments (...) explaining why it is permissible to expose children to some harm, and an argument concerning the appropriate balance between research harms and benefits. I argue that each of these is a necessary part of the justification for research with children, but that the argument concerning harms and benefits is under-developed. It relies on the concept of minimal risk, but minimal risk is inadequately justified. I propose an interpretation of minimal risk. I defend the idea that minimal risk should be interpreted according to the risks of daily life. I reject the most prominent defense of daily life, which claims that daily risks are morally relevant because they replace, rather than add to, the risks a child would ordinarily face. Instead, I propose that these risks are part of a reasonable trade-off between personal safety and our ability to pursue meaningful lives. I then examine whose daily life should be captured in the concept of minimal risk. I reject arguments that minimal risk should refer to healthy children or the subjects of the research and propose instead that the referent should be children who are not unduly burdened by their lives. I argue that children are not unduly burdened when they fare well and defend the idea that children fare well when they possess sufficiently high degrees of the substantive goods of childhood. I conclude by analyzing a controversial case study using my interpretation of minimal risk. I draw on this case to argue that my interpretation offers clear guidance for research ethics review and contributes to a determination that is more plausible than its rivals. (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)

Pediatric research without the potential for clinical benefit is vital to improving pediatric medical care. This research also raises ethical concern and is regarded by courts and commentators as unethical. While at least 10 justifications have been proposed in response, all have fundamental limitations. This article describes and defends a new justification based on the fact that enrollment in clinical research offers children the opportunity to contribute to a valuable project. Contributing as children to valuable projects can benefit individuals in (...) two ways. First, individuals may come to ?embrace? the contributions they made as children. Second, contributing to valuable projects can lead to a better overall life. Because these potential benefits can outweigh small research risks, they provide a justification for pediatric research without the potential for clinical benefit, when it poses low risks and has the potential to benefit others in important ways. (shrink)

This article reviews four areas of pediatric research in which we have identified questionable levels of allowable risk, exceeding those foreseen by the Commission. They are the following: the categorization of increasingly risky interventions as minimal risk in a variety of protocols; the increasing number of applications for federal panel review of research not otherwise approvable because of higher projected risk levels; research on asymptomatic at risk children; and the inclusion of children and adolescents in placebo-controlled trials for participants of (...) all ages without performing subgroup analysis. While embracing the imperative to include children in research is an encouraging step towards providing the pediatric population with effective medical care and finally eradicating the therapeutic orphan, we must ensure that this research does not become overly permissive. (shrink)

Pediatric participation in non-therapeutic research that poses greater than minimal risk has been the subject of considerable thought-provoking debate in the research ethics literature. While the need for more pediatric research has been called morally imperative, and concerted efforts have been made to increase pediatric medical research, the importance of protecting children from undue research risks remains paramount.United States research regulations are derived largely from the deliberations and report of the National Commission for the Protection of Human Subjects of Biomedical (...) and Behavioral Research. The authors of this report specifically designated children as a vulnerable population and suggested additional protections, most of which became U.S. law. One of the more contested sets of regulations surrounds non-therapeutic research, e.g., research that does not offer the potential for direct benefit to participants. Federal regulations allow local Institutional Review Boards to approve non-therapeutic research posing a minor increase above minimal risk when it involves children who have the disease or medical condition that the research addresses. (shrink)

Net‐risk pediatric research encompasses interventions and studies that pose risks and do not offer a compensating potential for clinical benefit. These interventions and studies are central to efforts to improve pediatric clinical care. Yet critics argue that it is unethical to expose children to research risks for the benefit of unrelated others. While a number of ethical justifications have been proposed, none have received widespread acceptance. This leaves funders with uncertainty over whether they should support and institutional review boards with (...) uncertainty over whether they should approve net‐risk pediatric research. To try to answer these questions, this article describes a justification that I previously proposed and considers two objections to it. This analysis reveals that the opportunity to contribute to a valuable project can justify exposing children to risks even though some trials turn out to be valueless and others turn out to be harmful. It follows that, to protect pediatric participants, institutional review boards need to assess whether trials have the potential to collect socially valuable information and whether they are likely to enroll and retain a sufficient number of participants. (shrink)

The U.S. federal regulations require investigators conducting nonbeneficial research to obtain the assent of children who are capable of providing it. Unfortunately, there has been no analysis of which children are capable of assent or even what abilities ground the capacity to give assent. Why should investigators be required to obtain the positive agreement of some children, but not others, before enrolling them in research that does not offer a compensating potential for direct benefit? We argue that the scope of (...) children's research decision making should be based on the principles of respect for autonomy and nonmaleficence. These principles imply that the threshold for assent should be fixed at 14 years of age, and a dissent requirement should be adopted for all children in the context of nonbeneficial research. (shrink)

The involvement of children in non-beneficial clinical research is extremely important for improving pediatric care, but its ethical acceptability is still disputed. Therefore, various pro-research justifications have been proposed throughout the years. The present essay aims at contributing to the on-going discussion surrounding children’s participation in non-beneficial clinical research. Building on Wendler’s ‘contribution to a valuable project’ justification, but going beyond a risk/benefit analysis, it articulates a pro-research argument which appeals to a phenomenological view on the body and vulnerability. It (...) is claimed that children’s bodies are not mere physical objects, but body-subjects due to which children, as persons, can contribute to research that may hold no direct clinical benefit to them even before they can give informed consent. (shrink)

Non-therapeutic research on children raises ethical concerns. Such research is not only conducted on individuals who are incapable of providing informed consent. It also typically involves some degree of risk or discomfort, without prospects of medically benefiting the participating children. Therefore, these children seem to be instrumentalized. Some ethicists, however, have tried to sidestep this problem by arguing that the children may indirectly benefit from participating in such research, in ways not related to the medical intervention as such. It has (...) been argued, for example, that non-therapeutic pediatric research does not instrumentalize the children enrolled since it has the prospects of furthering their moral development. We argue that this argument is far too undeveloped to be taken seriously. (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)

Guidelines around the world require children to provide assent for their participation in most research studies. Yet, little further guidance is provided on how review committees should implement this requirement, including which children are capable of providing assent and when the requirement for assent may be waived on the grounds that the research offers participating children the potential for important clinical benefit. The present paper argues that the assent requirement is supported by the importance of allowing children who are capable (...) to make their own decisions. This suggests children are capable of assent when they become able to understand the research in question. While development varies across individual children, existing data suggest most children develop this ability by approximately age 14. Until instruments are developed to assess the assent capacity of individual children, this age should be used as the threshold for assent. In addition, the importance of protecting children from harm suggests that the sustained dissent of all children, including those who are unable to provide assent, should be respected. While the assent requirement may be waived when research participation offers the potential for important medical benefit that is unavailable outside the research context, analysis suggests that children’s sustained dissent should be respected in all cases. (shrink)

Volume 20, Issue 4, May 2020, Page 118-120.