Much of the human research conducted in the United States or by U.S. researchers is regulated by the Common Rule. The Common Rule reflects the decision of 17 federal agencies, including the Department of Health and Human Services, to require that investigators follow the same rules for conducting human research., though there is significant overlap with the Common Rule.) Many of the obligations delineated in the Common Rule can be traced back to the work of the National Commission for the (...) Protection of Human Subjects of Biomedical and Behavioral Research. The National Commission was appointed in 1974 as part of the National Research Act in response to revelations about serious abuses involving human subjects, most notably the Tuskegee/United States Public Health Service Syphilis Study. (shrink)

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. (...) Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research. Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable. (shrink)

Bioethicists have long been concerned that seriously ill patients entering early phase (‘phase I’) treatment trials are motivated by therapeutic benefit even though the likelihood of benefit is low. In spite of these concerns, consent forms for phase I studies involving seriously ill patients generally employ indeterminate benefit statements rather than unambiguous statements of unlikely benefit. This seeming mismatch between attitudes and actions suggests a need to better understand research ethics committee members’ attitudes toward communication of potential benefits and risks (...) of early phase studies to potential subjects. We surveyed the members of two U.S. research ethics committees using a phase I gene transfer study scenario, and compared the results to a previous survey of potential subjects’ perceptions and attitudes toward benefit and risk for the same protocol. The results show that there is indeed a gap between the subjects’ perceptions and the committee members’ views on what is appropriate to be communicated to research subjects. This discrepancy is the product of both the commonly assumed optimism of the subjects and to a “protective pessimism” of the research ethics committee members. We discuss this discrepancy using “frameworks of trust” and demonstrate the need to incorporate these frameworks into the existing model of informed consent. (shrink)

The process of obtaining informed consent continues to be a contentious issue in clinical and public health research carried out in resource-limited settings. We sought to evaluate this process among human research participants in randomly selected active research studies approved by the School of Medicine Research and Ethics Committee at the College of Health Sciences, Makerere University.

The Office of Human Research Protections was not justified in issuing findings against the SUPPORT Institutions. Our community can learn from the evolving healthcare transformation into learning health systems by thinking about the novel ethical issues about standard of care research raised by the SUPPORT with the same spirit of quality improvement. The current regulatory framework and the concept of foreseeable research risks is insufficient to advance the debate about the ethics of randomization of standard clinical interventions. This article uses (...) the example of the Wisconsin cystic fibrosis randomized clinical trial for newborn screening trial to explore the distinctions between risks of research and clinical care and waivers of informed consent for randomization. Collaborative exploration of these complex policy issues is needed and further deliberation, community engagement, and social science research will be critical to advance novel approaches for informed consent. (shrink)

First-in-human research has several characteristics that require special attention with respect to ethics and human subjects protections. At least some nanomedical technologies may also have characteristics that merit special attention in clinical research, as other papers in this symposium show. This paper considers how to address these characteristics in the consent form and process for FIH nanomedicine research, focusing principally on experimental nanotherapeutic interventions but also considering nanodiagnostic interventions.It is essential, as a starting point, to recognize that the consent form (...) and process are by no means the primary protectors of human subjects. Instead, consideration of the form and content of informed consent becomes relevant only after a clinical trial has been reviewed and deemed scientifically and ethically acceptable.Two convergent types of challenges to informed consent are posed by nanomedicine FIH research. First, some issues appear generally applicable to FIH research, but have specific nanomedicine implications. (shrink)