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)

Unequal treatment of human research subjects is a significant ethical concern, because justice in research involving human subjects requires equal protection of rights and equal protection from harm and exploitation. Disputes sometimes arise concerning the issue of unequal treatment of research subjects. Allegedly unequal treatment occurs when subjects are treated differently and there is a genuine dispute concerning the appropriateness of equal treatment. Patently unequal treatment occurs when subjects are treated differently and there is not a genuine dispute about the (...) appropriateness of equal treatment. Allegedly unequal treatment will probably always occur in research with human subjects due to disagreements about fundamental questions of justice. The best way to deal with allegedly unequal treatment is to promote honest and open discussions of the issues at stake. Research regulations can help to minimize patently unequal treatment by providing rules for investigators, ethical review boards, institutions, and sponsors to follow. However, patently unequal treatment may still occur because the regulations are subject to interpretation. Federal agencies have provided interpretive guidance that can help promote consistent review and oversight of human subjects research. Additional direction may be needed on topics that are not adequately covered by current guidance or regulations. International guidelines can help promote equal treatment of human subjects around the globe. While minor variations in the treatment of research subjects should be tolerated and even welcomed, major ones (i.e. those that significantly impact human rights or welfare) should be avoided or minimized. (shrink)

Minimal risk is a central concept in the ethical analysis of research with children. It is defined as the risks “. . . ordinarily encountered in daily life . . . .” But the question arises: who is the referent for minimal risk? Commentators in the research ethics literature often answer this question by endorsing one of two possible interpretations: the uniform interpretation or the relative interpretation of minimal risk. We argue that describing the debate over minimal risk as a (...) disagreement between the uniform and the relative interpretation impedes progress on the identification of a justifiable referent for minimal risk. There are two main problems with this approach: constructing the debate over minimal risk as a disagreement between a uniform and a relative interpretation misconstrues the main difference between competing interpretations and neither the uniform nor the relative interpretation identifies one unique and consistent group of children as the referent for minimal risk. We conclude that progress on the debate over minimal risk requires that we abandon the uniform and relative interpretations and address the main moral problem at stake: whether healthy children or the subjects of the research should be the referent for minimal risk. (shrink)

: Despite its mandate on minimizing harms in clinical trials, the Common Rule provides little guidance as to how IRBs should evaluate risk. The Common Rule and derivative commentaries tend to conceptualize risk review as an expert-based endeavor aimed at an objective and universal evaluation of possible harm; they also have tended to locate risk in the research activity itself rather than in the context of the research. These views of risk conflict with scholarship showing that risk evaluations are socially (...) determined even among experts, that the context of harms can influence how persons evaluate risks, and that forums that approach risk assessment as a technical endeavor bracket from discussion the numerous values that ground risk judgments. Possible reforms are proposed for clinical trial risk review that would render it more inclusive of the different types of risks encountered and more attuned to the priorities of trial subjects. (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)