Institutional review boards and investigators are used to talking about risks of harm. Both low risks of great harm and high risks of small harm must be disclosed to prospective subjects and should be explained and categorized in ways that help potential subjects to understand and weigh them appropriately. Everyone on an IRB has probably spent time at meetings arguing over whether a three-page bulleted list of risk description is helpful or overkill for prospective subjects. Yet only a small fraction (...) of all the time and attention lavished on risk disclosure has been devoted to discussing whether and when potential benefit to subjects can reasonably be claimed and, if so, how it should be described in the consent form and process.Traditionally, IRBs and regulators have worked to ensure that clear lines can be drawn between research that, by definition, carries no potential for direct benefit — because it uses healthy volunteers or because it is not foreseeably focused on the development of treatments — and research that does have the development of effective treatments as its goal. (shrink)

Informed consent in clinical research is widely regarded as broken, but essential nonetheless. The most recent attempt to reform it comes as part of the first revisions to the Common Rule since it became truly “common” in 1991. This change, the addition of a “key information” requirement for most consent forms, is intended to support and promote a reasoned decision-making process by potential subjects. The key information requirement is both promising and problematic. It is promising because it encourages clarity and (...) honesty about research participation, creativity in information disclosure, and mutual learning through the investigator-subject relationship. It is problematic because those goals — which have remained aspirational since the beginning — may be difficult to achieve in what has become an excessively compliance-oriented regulatory regime. (shrink)

Nanomedicine is yielding new and improved treatments and diagnostics for a range of diseases and disorders. Nanomedicine applications incorporate materials and components with nanoscale dimensions where novel physiochemical properties emerge as a result of size-dependent phenomena and high surface-to-mass ratio. Nanotherapeutics and in vivo nanodiagnostics are a subset of nanomedicine products that enter the human body. These include drugs, biological products, implantable medical devices, and combination products that are designed to function in the body in ways unachievable at larger scales. (...) Nanotherapeutics and in vivo nanodiagnostics incorporate materials that are engineered at the nanoscale to express novel properties that are medicinally useful. These nanomedicine applications can also contain nanomaterials that are biologically active, producing interactions that depend on biological triggers. Examples include nanoscale formulations of insoluble drugs to improve bioavailability and pharmacokinetics, drugs encapsulated in hollow nanoparticles with the ability to target and cross cellular and tissue membranes and to release their payload at a specific time or location, imaging agents that demonstrate novel optical properties to aid in locating micrometastases, and antimicrobial and drug-eluting components or coatings of implantable medical devices such as stents. (shrink)

Clinical gene transfer research has both a unique history and a complex and layered system of research oversight, featuring a unique review body, the Recombinant DNA Advisory Committee. This paper briefly describes the process of decision-making about clinical GTR, considers whether the questions, problems, and issues raised in clinical GTR are unique, and concludes by examining whether the RAC's oversight is a useful model that should be reproduced for other similar areas of clinical research.Clinical GTR is governed by the same (...) oversight system as most clinical trials, with a significant addition: the RAC. Like other research with human subjects, GTR, if it is affiliated with a federally funded institution, must be approved by an institutional review board whose activities are governed by the common rule, that is, the federal regulations for protection of human subjects in research. Like other research intended to produce a drug, device, or biologic to be marketed in the United States, GTR is also overseen by the Food and Drug Administration. (shrink)

The three important target articles make a strong case for regarding racism as a public health crisis. Each calls for advocacy by the bi...

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme®, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme® and saline in the field and, still without consent, randomized between PolyHeme® and blood after arrival at an emergency department. The Federal regulations that govern the waiver (...) of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood - the standard treatment for hemorrhagic shock - is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)

In March 1996, the General Accounting Office issued the report Scientific Research: Continued Vigilance Critical to Protecting Human Subjects. It stated that “an inherent conflict of interest exists when physician-researchers include their patients in research protocols. If the physicians do not clearly distinguish between research and treatment in their attempt to inform subjects, the possible benefits of a study can be overemphasized and the risks minimized.” The report also acknowledged that “the line between research and treatment is not always clear (...) to clinicians. Controversy exists regarding whether certain medical procedures should be categorized as research.”This problem currently plagues gene transfer research. A few months prior to the GAO report, an ad hoc committee appointed by National Institutes of Health Director Harold Varmus expressed similar concerns in its assessment of NIH investment in research on gene therapy. (shrink)

On September 8, 2015, the Department of Health and Human Services issued a Notice of Proposed Rule Making to revise the Federal Policy for the Protection of Human Subjects, widely known as the “Common Rule.” The NPRM proposes several changes to the current system, including a dramatic shift in the approach to secondary research using biospecimens and data. Under the current rules, it is relatively easy to use biospecimens and data for secondary research. This approach systematically facilitates secondary research with (...) biospecimens and data, maximizing the capacity for substantial public benefit. However, it has been criticized as insufficiently protective of the privacy and autonomy interests of biospecimen and data sources. Thus, the NPRM proposes a more restrictive regime, although more so for biospecimens than data. Both the status quo and the NPRM's proposal are critically flawed. (shrink)

In much the same way that genomic technologies are changing the complexion of biomedical research, the issues they generate are changing the agenda of IRBs and research ethics. Many of the biggest challenges facing traditional research ethics today — privacy and confidentiality of research subjects; ownership, control, and sharing of research data; return of results and incidental findings; the relevance of group interests and harms; the scope of informed consent; and the relative importance of the therapeutic misconception — have become (...) important policy issues over the last 20 years because of the ways they have been magnified by genomic research efforts. Research that examines the ethical, legal, and social implications of human genomics research has become a burgeoning international field of scholarship over the last 20 years, thanks in part to its support first by the genome research funding bodies in the U.S. and then by national science agencies in other countries. (shrink)

The principle of informed consent is so firmly established in bioethics and biomedicine that the term was soon bowdlerized in common practice, such that engaging in the informed decision-making process with patients or research subjects is now often called “consenting” them. This evolution, from the original concept to the rather questionable coinage that makes consent a verb, reveals not only a loss of rhetorical precision but also a fundamental shift in the potential meaning, value, and implementation of the informed consent (...) process. Too often, the sharing of information has been replaced by the mere acquisition of agreement with the authority ostensibly offering a choice.Scholars of informed consent agree that its salience and its legitimacy derive from a fiduciary duty to inform, in order to respect, protect, and promote autonomous decision making by those to whom the duty is owed. (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)

Biodefense and emerging infectious disease animal research aims to avoid or ameliorate human disease, suffering, and death arising, or potentially arising, from natural outbreaks or intentional deployment of some of the world’s most dreaded pathogens. Top priority research goals include finding vaccines to prevent, diagnostic tools to detect, and medicines for smallpox, plague, ebola, anthrax, tularemia, and viral hemorrhagic fevers, among many other pathogens (National Institute of Allergy and Infectious Diseases [NIAID] priority pathogens). To this end, increased funding for conducting (...) research, developing research facilities, and purchasing (stockpiling) developed vaccines, diagnostic tools, and therapeutics .. (shrink)

Cluster randomised clinical trials present unique challenges in meeting ethical obligations to those who are treated at a randomised site. Obtaining informed consent for research within the context of clinical care is one such challenge. In order to solve this problem it is important that an informed consent process be effective and efficient, and that it does not impede the research or the healthcare. The innovative approach to informed consent employed in the COMPASS study demonstrates the feasibility of upholding ethical (...) standards without imposing undue burden on clinical workflows, staff members or patients who may participate in the research by virtue of their presence in a cluster randomised facility. The COMPASS study included 40 randomised sites and compared the effectiveness of a postacute stroke intervention with standard care. Each site provided either the comprehensive postacute stroke intervention or standard care according to the randomisation assignment. Working together, the study team, institutional review board and members of the community designed an ethically appropriate and operationally reasonable consent process which was carried out successfully at all randomised sites. This achievement is noteworthy because it demonstrates how to effectively conduct appropriate informed consent in cluster randomised trials, and because it provides a model that can easily be adapted for other pragmatic studies. With this innovative approach to informed consent, patients have access to the information they need about research occurring where they are seeking care, and medical researchers can conduct their studies without ethical concerns or unreasonable logistical impediments. Trial registration number [NCT02588664][1], recruiting. This article covers the development of consent process that is currentlty being employed in the study. [1]: https://clinicaltrials.gov/ct2/show/NCT02588664. (shrink)

Historian James H. Jones published the first edition of Bad Blood, the definitive history of the Tuskegee Syphilis Experiment, in 1981. Its clear-eyed examination of that research and its implications remains a bioethics classic, and the 30-year anniversary of its publication served as the impetus for the reexamination of research ethics that this symposium presents. Recent revelations about the United States Public Health Service study that infected mental patients and prisoners in Guatemala with syphilis in the late 1940s in order (...) to determine the efficacy of treatment represent only one of the many attestations to the persistence of ongoing, critical, and underaddressed issues in research ethics that Bad Blood first explored. Those issues include, but are not limited to: the complex and contested matters of the value of a given research question, the validity of the clinical trial designed to address it, and the priorities of science. (shrink)

_Bioethics, Public Moral Argument, and Social Responsibility_ explores the role of democratically oriented argument in promoting public understanding and discussion of the benefits and burdens of biotechnological progress. The contributors examine moral and policy controversies surrounding biomedical technologies and their place in American society, beginning with an examination of discourse and moral authority in democracy, and addressing a set of issues that include: dignity in health care; the social responsibilities of scientists, journalists, and scholars; and the language of genetics and (...) moral responsibility. (shrink)

In Shaping Our Selves, Erik Parens offers both a personal history of bioethics and a cleverly clarifying lens to train on disputes in bioethics about emerging technologies. The question for readers is whether this lens, as useful as it is, leaves too much outside our field of vision. Parens, born in 1957, comes from the first wave of bioethics scholars—those of us who still mostly happened into bioethics as a field, before it was sufficiently well-established to be identified as a (...) career pathway. Bioethics enjoys a fascinating diversity of origin stories, and Parens’s is no exception. He began his studies at the University of Chicago’s pan-disciplinary Committee on Social Thought, one of a handful.. (shrink)

One of my favorite bioethics quotes is nearing 50 years old:Let us not forget that progress is an optional goal, not an unconditional commitment, and that its tempo in particular, compulsive as it may become, has nothing sacred about it. Let us also remember that a slower progress in the conquest of disease would not threaten society, grievous as it is to those who have to deplore that their particular disease be not yet conquered, but that society would indeed be (...) threatened by the erosion of those moral values whose loss, possibly caused by too ruthless a pursuit of scientific progress, would make its most dazzling triumphs not worth having.Despite its age, this invocation seems to me increasingly relevant as time... (shrink)

At the time of this writing, a widely publicized, waived-consent trial is underway. Sponsored by Northfield Laboratories, Inc. (Evanston, IL) the trial is intended to evaluate the emergency use of PolyHeme?, an oxygen-carrying resuscitative fluid that might prevent deaths from uncontrolled bleeding. The protocol allows patients in hemorrhagic shock to be randomized between PolyHeme? and saline in the field and, still without consent, randomized between PolyHeme? and blood after arrival at an emergency department. The Federal regulations that govern the waiver (...) of consent restrict its applicability to circumstances where proven, satisfactory treatments are unavailable. Blood?the standard treatment for hemorrhagic shock?is not available in ambulances but is available in hospitals. The authors argue that the in-hospital stage of the study fails to meet ethical and regulatory standards. (shrink)