Although the principle of fair subject selection is a widely recognized requirement of ethical clinical research, it often yields conflicting imperatives, thus raising major ethical dilemmas regarding participant selection. In this paper, we diagnose the source of this problem, arguing that the principle of fair subject selection is best understood as a bundle of four distinct sub-principles, each with normative force and each yielding distinct imperatives: (1) fair inclusion; (2) fair burden sharing; (3) fair opportunity; and (4) fair distribution of (...) third-party risks. We first map out these distinct sub-principles, and then identify the ways in which they yield conflicting imperatives for the design of inclusion and exclusion criteria, and the recruitment of participants. We then offer guidance for how decision makers should navigate these conflicting imperatives to ensure that participants are selected fairly. (shrink)

1. The opinions expressed are the author's own. They do not reflect any position or policy of the National Institutes of Health, Public Health Service, Department of Health and Human Services, or any of the authors affiliated organizations.

Wittgenstein, in his famous critique of philosophy, noted that the influence of an idea can be such that it alters the way that we see the world. “It is like a pair of glasses on our nose through which we see whatever we look at,” he said. “It never occurs to us to take them off.” This view of the power of an idea suggests that the interpretation of an event, and what response this event calls for, can depend upon (...) the view one has of the world. A person who is naive about medical facts may, for example, interpret chest pain upon exertion as a sign that he is “overdoing it”; were he more medically knowledgeable, the same symptom might be interpreted as a possible indicator of coronary artery disease. The naive interpretation calls for rest; the informed interpretation calls for medical attention as well. (shrink)

Purposeful infection of healthy volunteers with a microbial pathogen seems at odds with acceptable ethical standards, but is an important contemporary research avenue used to study infectious diseases and their treatments. Generally termed ‘controlled human infection studies’, this research is particularly useful for fast tracking the development of candidate vaccines and may provide unique insight into disease pathogenesis otherwise unavailable. However, scarce bioethical literature is currently available to assist researchers and research ethics committees in negotiating the distinct issues raised by (...) research involving purposefully infecting healthy volunteers. In this article, we present two separate challenge studies and highlight the ethical issues of human challenge studies as seen through a well-constructed framework. Beyond the same stringent ethical standards seen in other areas of medical research, we conclude that human challenge studies should also include: independent expert reviews, including systematic reviews; a publicly available rationale for the research; implementation of measures to protect the public from spread of infection beyond the research setting; and a new system for compensation for harm. We hope these additions may encourage safer and more ethical research practice and help to safeguard public confidence in this vital research alternative in years to come. (shrink)

: Bioethicists have failed to understand the pervasively paternalistic character of research ethics. Not only is the overall structure of research review and regulation paternalistic in some sense; even the way informed consent is sought may imply paternalism. Paternalism has limits, however. Getting clear on the paternalism of research ethics may mean some kinds of prohibited research should be reassessed.