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)

We argue that the current ethical and regulatory framework for permissible risk levels in pediatric research can be helpfully understood in terms of children’s moral right to adequate protection from harm. Our analysis provides a rationale for what we propose as the highest level of permissible risk in pediatric research without the prospect of direct benefit: what we call “relatively minor” risk. We clarify the justification behind the usual standards of “minimal risk” and “a minor increase over minimal risk” and (...) explain why it is permissible to impose any risks at all on child participants who do not stand to benefit directly from enrollment in research. Finally, we illuminate some aspects of the concept of “best interests.”. (shrink)

The American Journal of Bioethics, Volume 12, Issue 1, Page 42-44, January 2012.

The American Journal of Bioethics, Volume 12, Issue 1, Page 40-42, January 2012.

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)

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)

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

The American Journal of Bioethics, Volume 12, Issue 1, Page 32-34, January 2012.

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)

Medical care of critically ill and injured infants and children globally should be based on best research evidence to ensure safe, efficacious treatment. In South Africa and other low and middle-income countries, research is needed to optimise care and ensure rational, equitable allocation of scare paediatric critical care resources.

The American Journal of Bioethics, Volume 12, Issue 1, Page 39-40, January 2012.

Biomedical research involving human subjects is an arena of conflicts of interests. One of the most important conflicts is between interests of participants and interests of future patients. Legal regulations and ethical guidelines are instruments designed to help find a fair balance between risks and burdens taken by research subjects and development of knowledge and new treatment. There is an universally accepted ethical principle, which states that it is not ethically allowed to sacrifice individual interests for the sake of society (...) and science. This is the principle of precedence of individual. But there is a problem with how to interpret the principle of precedence of individual in the context of research without prospect of future benefit involving children. There are proposals trying to reconcile non-beneficial research involving children with the concept of the best interests. We assert that this reconciliation is flawed and propose an interpretation of the principle of precedence of individual as follows: not all, but only the most important interests of participants, must be guaranteed; this principle should be interpreted as the secure participant standard. In consequence, the issue of permissible risk ceiling becomes ethically crucial in research with incompetent subjects. (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)

The American Journal of Bioethics, Volume 12, Issue 1, Page 35-36, January 2012.

:To what extent, if any, should minors have a say about whether they participate in research that offers them no prospect of direct benefit? This article addresses this question as it pertains to minors who cannot understand enough about what their participation would involve to make an autonomous choice, but can comprehend enough to have and express opinions about participating. The first aim is to defend David Wendler and Seema Shah’s claim that minors who meet this description should not be (...) offered a choice about whether they participate. The second aim is to show, contra Wendler and Shah, that the principle of nonmaleficence requires more with respect to giving these minors a say than merely respecting their dissent. Additionally, it requires that investigators obtain affirmation of their non-dissent. This addresses intuitive concerns about denying children a choice, while steering clear of the problems that arise with allowing them one. (shrink)

The American Journal of Bioethics, Volume 12, Issue 1, Page 44-46, January 2012.

Evidence-based nursing practice is based on three pillars: the available research, known preferences of the patient or patient group and the professional experience of the nurse. For all pillars, research is the tool to expand the evidence we have, but when implementing evidence-based practice in paediatric nursing two of the pillars demand that children are included as respondents: practice research on the nursing interventions in paediatrics and the preferences of patients, something recognized by scholars and practitioners. But including a vulnerable (...) group as children in nursing research raises specific ethical issues that need to be considered by researchers. What are ethical considerations that are currently raised about doing research with children and what do we learn by synthesizing the narrative of these studies of why the issues are raised and which solutions can be offered for these issues? In this article, considerations on three ethical principles according to the Belmont report are described by examining recent research. Twenty-one studies were found addressing relevant ethical aspects including vulnerability, gaining consent, designing quantitative or qualitative research methods and considerations regarding the execution of the study. Ethical considerations should be much more a case of continuous awareness and attitude, then box-ticking exercise, although there are sufficient international guidelines available specifically for research that includes children to aid researchers. (shrink)