Most of the literature on phase one trials has focused on ethical and safety issues in research on patients with advanced cancer, but this article focuses on healthy, adult subjects. The article makes six specific recommendations for protecting the rights and welfare of healthy subjects in phase one trials: 1) because phase one trials are short in duaration (usually 1 to 3 months), researchers should gather more data on the short-term and long-term risks of participation in phase one studies by (...) healthy subjects; 2) researchers should develop strict inclusion/exclusion criteria that exclude unhealthy or vulnerable subjects, such as decisionally impaired people, in phase one studies; 3) subjects should not participate in more than one phase one study at the same time and should wait at least 30 days between participating in different studies; 4) researchers should develop a database to keep track of phase one participants; 5) subjects should be guaranteed a minimum wage equivalent to the equivalent type of unskilled labor, but there should be no upper limits on wages; and 6) subjects should be allowed to engage in collective bargaining with research sponsors. *Disclaimer: The ideas and opinions expressed in this article are the authors' personal views and do not represent the views of the National Institute of Environmental Health Sciences, the National Institutes of Health, or the United States government. (shrink)

This paper considers what are the appropriate limits of parental or guardian proxy consent for a child's participation in medical or social science research. Such proxy consent, it is proposed, is invalid in regards “non-therapeutic research.” The latter research may add to scientific knowledge and/or benefit others, but any benefit to the child research participant is but a coincidental theoretical possibility and not a primary objective. Research involving children, without intended and acceptable prospect of beneficial outcome to the individual participant, (...) even if with negligible risk, does not meet the test for “best interests.” Proxy consent for children's involvement in research is justifiable only when given for and on behalf of the child in his or her best interest to enhance the child's well-being. Only in the latter case is the parental proxy consent situation analogous in regards key criteria to a competent individual consenting to research participation. (shrink)

An informed consent and voluntary assent in biomedical research with adolescents is contingent on a variety of factors, including adolescent and parent perceptions of research risk, benefit, and decision-making autonomy. Thirty-seven adolescents with asthma and their parents evaluated a high or low aversion form of a pediatric asthma research vignette and provided an enrollment decision; their perceptions of family influence over the participation decision; and evaluations of risk, aversion, benefit, and burden of study procedures. Adolescents and their parents agreed on (...) research participation decisions 74% of the time, yet both claimed ultimate responsibility for the participation decision. Both rated most study procedures as significantly more aversive than risky. Parents were more likely to rate aspects of the hypothetical study as beneficial and to provide higher risk ratings for procedures. Disagreements concerning research participation decisions and decision-making autonomy have implications for the exercise of voluntary assent in biomedical research. (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)

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)

The papers in this volume are largely about research ethics and cover questions of consent, reproduction, pediatric research, ethical codes, and clinical relationships. Half the papers have this common aspect: they are conservative—in the sense of supporting the standard, prevailing, or popular view—but they shift the focus—supporting the standard views in terms of moral factors generally neglected by the literature. The volume provides a diverse set of papers for the reader: variously addressing abstract and concrete problems from within different philosophical (...) traditions. (shrink)

How should the definition of “minimal risk” in the federal research regulations be interpreted in regard to pregnant women and fetuses? Surprisingly, there has been little discussion of this question. There is, after all, a substantial amount of published work addressing the question of how “minimal risk” should be interpreted. Similarly, there is a large body of literature on the ethics of research involving pregnant women and fetuses, particularly maternal-fetal surgery. However, in neither of these bodies of work can one (...) find an analysis of minimal risk in regard to fetuses or pregnant women.The concept of minimal risk is defined in the regulations as follows:Minimal risk means that the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upon concentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim (...) of this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upoconcentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of (...) this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

The concept of minimal risk has been used to regulate and limit participation by adolescents in clinical trials. It can be understood as setting an absolute standard of what risks are considered minimal or it can be interpreted as relative to the actual risks faced by members of the host community for the trial. While commentators have almost universally opposed a relative interpretation of the environmental risks faced by potential adolescent trial participants, we argue that the ethical concerns against the (...) relative standard may not be as convincing as these commentators believe. Our aim is to present the case for a relative standard of environmental risk in order to open a debate on this subject. We conclude by discussing how a relative standard of environmental risk could be defended in the specific case of an HIV vaccine trial among adolescents in South Africa. (shrink)

Contemporary research ethics policies started with reflection on the atrocities perpetrated upoconcentration camp inmates by Nazi doctors. Apparently, as a consequence of that experience, the policies that now guide human subject research focus on the protection of human subjects by making informed consent the centerpiece of regulatory attention. I take the choice of context for policy design, the initial prioritization of informed consent, and several associated conceptual missteps, to have set research ethics off in the wrong direction. The aim of (...) this paper is to sort out these confusions and their implications and to offer instead a straightforward framework for considering the ethical conduct of human subject research. In the course of this discussion I clarify different senses of autonomy that have been confounded and present more intelligible justifications for informed consent. I also take issue with several of the now accepted dogmas that govern research ethics. These include: the primacy of informed consent, the protection of the vulnerable, the substitution of beneficence for research's social purpose, and the introduction of an untenable distinction between innovation and research. (shrink)

The idea that research with human participants should benefit society has become firmly entrenched in various regulations, policies, and guidelines, but there has been little in-depth analysis of this ethical principle in the bioethics literature. In this paper, I distinguish between strong and weak versions and the social benefits principle and examine six arguments for it. I argue that while it is always ethically desirable for research with human subjects to offer important benefits to society, the reasonable expectation of substantial (...) public benefit should be a necessary condition for regarding research as ethical only when it imposes more than minimal risks on non-consenting subjects; or it is supported by public resources. (shrink)

Many pediatric research regulations, including those of the United States, the Council for International Organizations of Medical Science, and South Africa, offer similar rules for review board approval of higher hazard studies holding out no therapeutic or direct benefit to children with disorders or conditions. Authorization requires gaining parental permissions and the children’s assent, if that is possible, and showing that these studies are intended to gain vitally important and generalizable information about children’s conditions; it also requires limiting the risks (...) of harm to no more than a “minor increase over minimal risk” and showing the study is commensurable with the children’s experiences. For convenience, these investigations will be called “no benefit, higher hazard” studies.Despite the existence of these policies for decades, studies show that review boards’ judgments vary about what “no benefit, higher hazard” studies should be approved. (shrink)

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