To protect children in research, procedures that are not administered in the medical interests of a child must be restricted. The risk threshold for these procedures is generally measured according to the concept of minimal risk. Minimal risk is often defined according to the risks of “daily life.” But it is not clear whose daily life should serve as the baseline; that is, it is not clear to whom minimal risk should refer. Commentators in research ethics often argue that “minimal (...) risk” should refer to healthy children or the subjects of the research. I argue that neither of these interpretations is successful. I propose a new interpretation in which minimal risk refers to children who are not unduly burdened by their daily lives. I argue that children are not unduly burdened when they fare well, and I defend a substantive goods account of children’s welfare. (shrink)

Controlled human infection model (CHIM) studies involve the intentional exposure of healthy research volunteers to infectious agents. These studies contribute to knowledge about the cause or development of disease and to the advancement of vaccine research. But they also raise ethical questions about the kinds of risks that should be permissible and whether limits should be imposed on research risks in CHIM studies. Two possible risk thresholds have been considered for CHIM studies. The first suggests constraining ethically permissible risks according (...) to a minimal risk threshold and the second endorses a higher risk threshold that excludes irreversible or fatal infections. I argue that neither of these thresholds is persuasive and situate questions about risk thresholds in CHIM studies within a broader debate about permissible risks in research. I argue that risks in CHIM studies should be constrained according to limits on research risks that do not offer corresponding benefits in all studies rather than developing a unique risk threshold for CHIM studies. I then propose five recommendations for the ethical assessment of risk in CHIM studies. (shrink)

COVID-19 poses an exceptional threat to global public health and well-being. Recognition of the need to develop effective vaccines at unprecedented speed has led to calls to accelerate research pathways ethically, including by conducting challenge studies ) with SARS-CoV-2. Such research is controversial, with concerns being raised about the social, legal, ethical and clinical implications of infecting healthy volunteers with SARS-CoV-2 for research purposes. Systematic risk evaluations are critical to inform assessments of the ethics of any proposed SARS-CoV-2 CHIs. Such (...) evaluations will necessarily take place within a rapidly changing and at times contested epidemiological landscape, in which differing criteria for the ethical acceptability of research risks have been proposed. This paper critically reviews two such criteria and evaluates whether the use of effective treatment should be a necessary condition for the ethical acceptability of SARS-CoV-2 CHIs, and whether the choice of study sites should be influenced by COVID-19 incidence levels. The paper concludes that ethical evaluations of proposed SARS-CoV-2 CHIs should be informed by rigorous, consultative and holistic approaches to systematic risk assessment. (shrink)

Ethics guidelines and commentary suggest that a central function of research ethics committees is to assess the scientific merit of the protocols they review. However, some commentators object to this role, and evidence suggests that the assessment of scientific merit is a significant source of confusion and animosity between ethics committees and clinical investigators. In this essay, we argue that ethics committees should assess the scientific value and validity of research protocols and that new decision-making tools are needed to help (...) them do so in a systematic, transparent, and reliable way. We present a novel ethical framework that can assist in this task. (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)

Infants are unable to make their own decisions or express their own wishes about medical procedures and treatments. They rely on surrogates to make decisions for them. Who should be the decision-maker when an infant’s biological parents are also minors? In this paper, we analyse a case in which the biological mother is a child. The central questions raised by the case are whether minor parents should make medical decisions on behalf of an infant, and if so, what are the (...) limits to this decision-making authority? In particular, can they refuse treatment that might be considered best for the infant? We examine different ethical arguments to underpin parental decision-making authority; we argue that provided that minor parents are capable of fulfilling their parental duties, they should have a right to make medical decisions for their infant. We then examine the ethical limits to minor parents’ decision-making authority for their children. We argue that the restricted authority that teenagers are granted to make medical decisions for themselves looks very similar to the restricted autonomy of all parents. That is, they are permitted to make choices, but not harmful choices. Like all parents, minor parents must not abuse or neglect their children and must also promote their welfare. They have a moral right to make medical decisions for their infants within the same ‘zone of parental discretion’ that applies to adult parents. We conclude that adult and minor parents should have comparable decision-making authority for their infants. (shrink)

Most agree that clinical research offers one of the best prospects of improving pediatric medicine. Most also agree that children may be exposed to some degree of risk while participating in clinical trials. But the degree of risk that should be permitted and the reasons for which it should be permitted remain controversial. In this paper, I examine a central risk threshold in research with children—the threshold constraining risks that do not offer research subjects the prospect of direct medical benefit. (...) That is, the threshold for research risks undertaken in the interests of deriving valuable knowledge that may benefit future children, but not the research subjects themselves. I examine competing... (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)

Ethics has been identified as a central reason for choosing the stepped wedge trial over other kinds of trial designs. The potential advantage of the stepped wedge design is that it provides all arms of the trial with the active intervention over the course of the study. Some groups receive it later than others, but the study intervention is not withheld from any group. This feature of the stepped wedge design seems particularly ethically advantageous in two instances: when the study (...) intervention appears especially likely to be effective and when the consequences of not receiving the intervention may be dire. But despite an increase in the use of the stepped wedge design and appeals to its ethical superiority as the motivation for its selection, there has been limited attention to the stepped wedge trial in the ethics literature. In the following, I examine whether there are persuasive ethical reasons to prefer or to require a stepped wedge trial. I argue that while the stepped wedge design is ethically permissible, it is not morally superior to other kinds of trials. To this end, I examine the ethical justification for providing, withholding, and delaying interventions in research. (shrink)

The use of charged-particle radiation therapy is an increasingly important development in the treatment of cancer. One of the most pressing controversies about the use of this technology is whether randomised controlled trials are required before this form of treatment can be considered to be the treatment of choice for a wide range of indications. Equipoise is the key ethical concept in determining which research studies are justified. However, there is a good deal of disagreement about how this concept is (...) best understood and applied in the specific case of CPRT. This report is a position statement on these controversies that arises out of a workshop held at Wolfson College, Oxford in August 2011. The workshop brought together international leaders in the relevant fields , including proponents on both sides of the debate, in order to make significant progress on the ethical issues associated with CPRT research. This position statement provides an ethical platform for future research and should enable further work to be done in developing international coordinated programmes of research. (shrink)

The American Journal of Bioethics, Volume 11, Issue 6, Page 25-27, June 2011.

Despite more than a century of research on sexual dysfunction, there has been limited attention to ethical concerns. This is problematic because sex research involves complex ethical questions that generate confusion for ethics review and have not been addressed by ethical guidelines. We analyze two questions. First, does sexual content raise the risk profile of a research protocol? We argue that there is nothing inherent in sexual content that makes a study high risk and that many sexual dysfunction studies involve (...) no more than minimal risk. Second, we ask whether research interventions that involve seeing participants undressed or having physical contact with a research subject are permissible? We argue that these interventions raise an important ethical challenge—they often involve sexual dysfunction researchers engaging in interventions that would not be conducted in their standard practice. To resolve this, we propose an expertise-based account of the permissibility of sexual dysfunction research. (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)

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 central problems concerning research with children is the delineation of appropriate levels of risk exposure. In the U.S. Code of Federal Regulations, the "minimal risk" concept serves as an anchoring measure for allowable risk. While the regulations sought to promote a balance between scientific advances and the protection of children's vulnerable status, ambiguities in the language of the regulations and the regulatory definition of "minimal risk" have given rise to a great deal of confusion. Research ethics boards (...) and the medical community espouse a multitude of varying opinions regarding the interpretation and application of the federal regulations with more recent research demonstrating an apparent increase in risk without corresponding benefit in pediatric research. Informed by ethical theory, law, and science, this project analyzes the apparent increase in allowable risk, calls for a reassessment of the concept of "minimal risk," and recommends modifications to the federal regulations. (shrink)

Iris Marion Young, On female body experience: “Throwing like a girl” and other essays, New York: Oxford University Press, 2005, reviewed by Ariella Binik.

Human challenge studies, in which human research subjects are intentionally exposed to pathogens to contribute to scientific knowledge, raise many ethical complexities. One controversial question is whether it is ethically permissible to include children as participants. Commentary of the past decades endorses the exclusion of children, while new guidance suggests that pediatric human challenge studies can be ethically permissible. This paper argues that neither children's exclusion nor their inclusion are well justified. I examine and reject three arguments for exclusion, but (...) suggest that these arguments establish pediatric human challenge studies as a complex ethical category of research that requires caution. I then argue for a strong presumption against children's inclusion, by drawing on an analogy to children's inclusion in phase I trials, emphasizing a requirement of necessity, and suggesting that accommodating children's vulnerability promotes an age de-escalation approach for pediatric human challenge studies research. In the final section, I suggest a procedure for ethics review. (shrink)