Practical implications

In the previous chapter I ask, who should be the referent for minimal risk? I answer that the referent should be a group of children who are not unduly burdened by their daily lives. I argue that children who are not unduly burdened are those who fare well and

defend a substantive good theory of children’s welfare. In this section, I examine a related question: what are the implications of a child failing to fare well enough to be the referent for minimal risk? To put it another way, what happens when a research ethics board determines that a group of children should not be the referent for minimal risk?

One possible implication of a research ethics board determining that a child fails to fare sufficiently well is that a child should not be included in research at all. That is, if a child should not be the referent for minimal risk then she should not be a research participant full stop. One might reach this conclusion by reasoning that when a child is unduly burdened by her daily life, imposing on her the additional burdens of research would be unjust. This conclusion is problematic. It suggests that many, if not most sick children, and all those suffering from diseases and disorders whose medical treatment involves significant burdens should be excluded from research. But excluding these children from research would complicate or prevent valuable research—including research on children’s cancer, diabetes, cystic fibrosis, and meningitis—which would delay the improvement of medical treatment of current and future children. Further, if this conclusion were correct, then it would follow that a great deal of the current research with children (which focuses primarily on sick children) is morally impermissible.

However, it is not the case that children who fail to fare well should be excluded from research participation. Identifying the referent for minimal risk is part of the broader project of assessing whether a research protocol involves a reasonable balance between harms and benefits. The analysis of harms and benefit aims to establish the degree of risk that is permissible in various research procedures; it is a requirement of the broader ethical principle of beneficence, which aims to ensure that benefits to research subjects are maximized and harms are minimized (Belmont Report, 1979).

Analyses of the principle of beneficence are separable from considerations about the fair selection of research subjects, which falls under the broader ethical principle of justice (and concerns the fair distribution of the burdens and benefits of research)

(Belmont Report, 1979). Both of the principles of beneficence and justice are important; fulfilling the requirement of each is necessary for the ethical justification of a proposed research protocol. But they are separable and have different purviews. Harm benefit assessments govern the appropriate risk limits for research procedures. And this analysis

is separable from and presupposes that a research ethics board will also consider and pass judgment on who should be the morally appropriate subject population for a trial.

The relationship between the principles is not always straightforward. Insofar as identifying the referent for minimal risk requires us to identify a group of children whose daily lives are morally relevant, it involves the selection of a group of children. But this group is morally relevant not because they are appropriate research subjects for a given protocol. Instead, the relevance of this group of children is that their daily lives involve morally defensible degrees of risk. And consequently, their daily experiences are a justifiable standard for permissible degrees of risk in non-therapeutic research

procedures. Insofar as the identification of a referent for minimal risk is part of a harm- benefit assessment, it should not necessarily influence the selection of morally

appropriate research subjects. That said, the moral justification of a protocol will always depend on also fulfilling the justice requirement to choose research subjects fairly.

This analysis suggests that when a child does not fare well enough to be the referent for minimal risk, she should not necessarily be excluded from research

participation. A research ethics board may find that it is consistent with the requirements of justice to provide a child who does not fare well enough to be the referent for minimal risk with access to participation in a given trial. For example, a child undergoing

chemotherapy for treatment of a serious cancer probably does not possess sufficient amounts of the substantive goods of childhood to fare well. But a research ethics board may still determine that she is an appropriate subject in a trial examining new methods for managing the side effects of chemotherapy. In this kind of case, the child’s failure to fare well does not exclude her from research. But it does require that she receive

additional protections in research. She must not be exposed to non-therapeutic research procedures involving risks comparable to those she experiences in her own daily life (given that it likely involves risks that are higher than the morally justifiable degrees of daily risks faced by children who fare sufficiently well). Instead, she must only be exposed to non-therapeutic procedures involving no more risk than that which is experienced in the daily lives of children who do fare sufficiently well.

It is worth considering whether this analysis differs with respect to the other prominent interpretations of the referent for minimal risk. Identifying the referent as the

subjects of the research has no mechanism by which to provide additional research protections for a child heavily burdened by her disease. It follows that when the eligible study population for a trial is children undergoing chemotherapy for a serious cancer, then the risks of non-therapeutic research procedures should be comparable to the risks that child faces in her daily life. Thus, if a child’s (imprudent) parents or guardians agreed to enroll her in this trial, she might face risks comparable to those of

chemotherapy (e.g. significant discomfort or death) in research procedures administered without the prospect of benefit. These kinds of non-therapeutic risks are too high, but not clearly prohibited by the subjects of the research interpretation. Both my interpretation and the subjects of the research interpretation permit the enrollment of sick children in research, but my interpretation offers better protections than the subject of the research interpretation for sick children in research.

However, identifying the referent as healthy children yields similar results as my proposal. That is, if a child is identified as sick—and accordingly, her daily experiences are deemed inappropriate as a comparator for the risks of non-therapeutic research procedures—she is not necessarily excluded from research participation. Instead, she might be included but only on the condition that the risks of non-therapeutic procedures are limited to those comparable to the risks healthy children face in daily life. Thus, the implications of a child failing to fare well enough to be the referent for minimal risk are that if she is included in a trial, she may only be exposed to non-therapeutic procedures involving risks that are comparable to the daily experiences of children who fare well (and not her own higher risk daily experiences). The main point is that the referent for minimal risk is a reference class of children whose daily lives serve as a justifiable measure for the risks of non-therapeutic research procedures; identifying a group of children as the referent does not necessarily influence whether these children are appropriate research subjects.

5.1.1 Implications for therapeutic research procedures

Another important question about the implications of my argument is: in what ways, if any, does my proposed interpretation inform the analysis of research protocols involving therapeutic procedures? In chapter 1, I situate my analysis of minimal risk within a

broader system of analyzing harms and benefits. This system—component analysis—is based on the idea that a great deal of clinical research involves both therapeutic and non- therapeutic procedures and develops an approach found within the work of the National Commission. Therapeutic procedures and non-therapeutic procedures should be

demarcated and are governed by separate moral rules (Freedman, Fuks, & Weijer, 1991; Weijer, 2000).

Minimal risk is a moral threshold governing the permissibility of non-therapeutic procedures on vulnerable populations. Accordingly, it exerts influence only over

procedures that are administered in the exclusive interests of the study and not an individual subject. In other words, my interpretation of minimal risk elaborates on the assessment of non-therapeutic procedures. It has no direct impact on the moral

assessment of therapeutic procedures, but it does help to identify the conditions under which a trial including therapeutic procedures may be found permissible. I’ve argued that all trials including therapeutic procedures also include non-therapeutic research

procedures. Further, to be ethically permissible, both the therapeutic and non-therapeutic procedures of a trial must be deemed permissible. Thus, my analysis of minimal risk helps to explain the conditions under which a trial involving non-therapeutic procedures or a mixture of therapeutic and non-therapeutic procedures can be found ethically permissible.