Emily A. Largent

Going off-label without venturing off-course: evidence and ethical off-label prescribing.

F OLLOWING US FOOD and Drug Administration (FDA) approval, clinicians may lawfully prescribe a drug or biologic agent for treatment regimens not specified in the approved labeling or package insert. This is known as off-label use. A recent study found that for 160 common drugs in the United States, off-label use accounted for 21% of all prescriptions. Many off-label uses are accepted as standard of care, for example, use of -blockers for congestive heart failure. Many other offlabel uses, however, lack evidence of clinical efficacy. In light of growing concerns about appropriateness and cost, off-label use has been identified as 1 aspect of problematic drug prescribing. Currently, there is little guidance to distinguish clearly between of f label uses that are wel l supported by evidence and those that are not. In this article, we address that gap at the level of the practicing physician. First, we identify characteristics of off-label use that signal the need for greater scrutiny. Second, we propose a framework that differentiates types of off-label use based on the available evidence and links the level of evidence to specific requirements for ethical prescribing. Although specifically targeted to off-label use, this framework is applicable to the general issue of appropriate prescribing in light of adequate evidence of risks and benefits.

Misconceptions About Coercion and Undue Influence: Reflections on the Views of IRB Members

Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue influence. Upon critical evaluation of the cogency of ethical concerns regarding payment, as reflected in our survey results, we found expansive or inconsistent views about coercion and undue influence that may interfere with valuable research. In particular, respondents appear to believe that coercion and undue influence lie on a continuum; by contrast, we argue that they are wholly distinct: whereas undue influence is a cognitive distortion relating to assessment of risks and benefits, coercion is a threat of harm. Because payment is an offer, rather than a threat, payment is never coercive.

A prescription for ethical learning

We argued last year in this journal that extensive integration of research and care is a worthy goal of health system design, and we second the call from Ruth Faden and colleagues to move toward learning health care systems. As they recognize, learning health care systems demand the coordination of research and medical ethics—two sets of normative commitments that have long been considered distinct. In offering a novel ethics framework for such systems, Faden et al. advance the scholarly debate about how best to do this and challenge us to think more deeply about its practical implications. However, we believe that at least three issues they raise require additional attention. First, the research-care distinction has more normative bite than they are willing to concede. Second, the role for independent oversight requires clarification. Finally, they neglect the concept of stewardship as a guiding obligation of learning health care systems.

EBOLA and FDA: reviewing the response to the 2014 outbreak, to find lessons for the future

Abstract In 2014, West Africa confronted the most severe outbreak of Ebola virus disease (EVD) in history. At the onset of the outbreak—as now—there were no therapies approved by the U.S. Food and Drug Administration (FDA) for prevention of, post-exposure prophylaxis against, or treatment of EVD. As a result, the outbreak spurred interest in developing novel treatments, sparked calls to use experimental interventions in the field, and highlighted challenges to the standard approach to FDA approval of new drugs. Although the outbreak was geographically centered in West Africa, it showcased FDAs global role in drug development, approval, and access. FDAs response to EVD highlights the panoply of agency powers and demonstrates the flexibility of FDAs regulatory framework. This paper evaluates the strengths and weaknesses of FDAs response and makes policy recommendations regarding how FDA should respond to new and re-emerging public health threats. In particular, it argues that greater emphasis should be placed on drug development in interoutbreak periods and on assuring access to approved products. The current pandemic of Zika virus infection is but one example of an emerging health threat that will require FDA involvement in order to achieve a successful response.

Who Should Get the Last PICU Bed

Administrators sometimes face ethical dilemmas about the allocation of institutional resources. One such situation is when elective surgery cases require reserved ICU beds and the ICU is full. Such situations arise frequently in children’s hospitals today. They are sometimes complicated by questions about whether every patient in the ICU belongs there. We present such a situation and responses from Mark Del Becarro, Vice President for Medical Affairs at Seattle Children’s Hospital; Aaron Wightman, a nephrology fellow and bioethicist at Seattle Children’s Hospital; and Emily Largent, a doctoral student in the joint JD/PhD Program in Health Policy at Harvard University.

Recently proposed changes to legal and ethical guidelines governing human subjects research

In recent months, updates have been proposed to two important documents in human subjects research oversight: the Federal Policy for the Protection of Human Subjects or ‘Common Rule’1 and the Council for International Organizations of Medical Sciences (CIOMS) Ethical Guidelines for Biomedical Research2 (hereafter, ‘CIOMS Guidelines’). The two proposals have garnered significant attention within the research community because, if finalized, they would be the first major revisions to these documents since 1991 and 2002, respectively. Moreover, they include substantive changes that could have far-reaching effects on the conduct of human subjects research.

Blind Peer Review by Academic Journals

The peer review process is central to the advancement of scholarly knowledge and is vital to the advancement of individual careers. With so much at stake, it is important to examine, and reexamine, issues pertaining to the fairness and quality of peer review on an ongoing basis. One central issue is blinding. In this chapter, we review evidence from across a variety of disciplines on the efficacy of blinding as a means of reducing bias and yielding higher quality reviews. We find that evidence is, in general, inconclusive. Most, though not all, benefits attributable to blinding are contingent on blinding being successful. Therefore, we also review evidence on the feasibility and efficacy of blinding and find that blinding is moderately effective. We conclude by examining the views of stakeholders in the peer review process and determine that, although the evidence is mixed, there is broad support for blinding.

Health Care Organizations and the Power of Procedure

Rationing refers to “any explicit or implicit measures that allow people to go without beneficial health care services” (Ubel and Goold 1998). In our health care system, some rationing is both ethi...

Is it ethical to hire sherpas when climbing Mount Everest

A medical ethical approach may be useful, but the jury’s still out, writes Emily Largent

Comparative effectiveness research: what effects for nurses?

Americas present level of health care spending is unsustainable. The rising costs of health care would be less concerning if there was evidence suggesting that more spending made Americans healthier; the evidence, however, suggests otherwise. The purpose of this article is to describe one tool that can potentially address quality and cost concerns for all health care professionals, including critical-care nurses.