U.S. Food and Drug Administration policy prohibits blood donation from men who have had sex with men even one time since 1977. Growing moral criticism claims that this policy is discriminatory, a claim rejected by the FDA. An overview of U.S. blood donation, recent donor deferral policy, and the conventional ethical debate introduce the need for a different approach to analyzing discrimination claims. I draw on an institutional understanding of injustice to discern and describe five features of (...) the MSM policy and its FDA context that contribute to its discriminatory effect. I note significant similarities in the 1980s policy of deferring Haitians, suggesting an historical pattern of discrimination in FDA deferral policy. Finally, I point to changes needed to move toward a nondiscriminatory deferral policy. (shrink)

This paper argues that the Food and Drug Administration’s (FDA) policy for health and wellness apps is ethically problematic. Currently, the FDA does not regulate health and wellness apps that are not intended for medical use. As a result of this hands‐off policy, preventing harm to consumers is left primarily to developers and app marketplaces. We argue that the FDA’s duties to prevent harm and maintain accountability to the American public require that they play a much stronger role. (...) We also discuss concerns about efficiency and fostering innovation, and argue that while they should help shape FDA regulation of health and wellness apps, they do not justify complete absence of FDA involvement. -/- . (shrink)

Transparency requires more than disclosure of data. It requires a mechanism and policy for conveying information to the public. In order for the aims of the excellent report of the FDA Transparency Working Group to be realized, a publicity initiative will need to accompany the plan of action. The FDA will need to actively convey information about the evidence concerning benefit-risk profiles of drugs, sometimes pointing out misleading claims by manufacturers or sponsors. In other cases, the FDA will need (...) to make available its procedures, including possible conflicts of interest, not only in drug approval, but also in guidance documents and in rulemaking. Transparency as a process of letting the public see into the agency should be accompanied by a proactive strategy of distributing information about the products regulated by the agency. (shrink)

The diagnosis of idiopathic short stature refers to children who are considerably shorter than average without any identified medical reason. The US Food and Drug Administration authorised marketing of recombinant human growth hormone for ISS in 2003, while the European Medicines Agency refused it in 2007. This paper examines the arguments for these decisions as detailed in selected FDA and EMA documents. It combines argumentative analysis with an approach to policy analysis called ‘What’s the problem represented to be’. It (...) argues that the FDA presents its approval as an argument for equity of access to the treatment, describing short stature as a potential disadvantage, and assuming that height normalisation is a clinically meaningful result. The EMA, instead, refuses marketing authorisation with an argument that there is an imbalance of risks and benefits, describing ISS as a healthy condition, and arguing that hGH should provide some psychosocial and/or quality of life benefits to children with ISS other than height gain. This paper then discusses how these arguments could be read through different models of disability, particularly through the medical model of disability and the relational, experiential, and cultural understandings of disability. (shrink)

The US National Institute of Health’s Human Microbiome Project aims to use genomic techniques to understand the microbial communities that live on the human body. The emergent field of microbiome science brought together diverse disciplinary perspectives and technologies, thus facilitating the negotiation of differing values. Here, we describe how values are conceptualized and negotiated within microbiome research. Analyzing discussions from a series of interdisciplinary workshops conducted with microbiome researchers, we argue that negotiations of epistemic, social, and institutional values were inextricable (...) from the reflective and strategic category work that defined and organized the microbiome as an object of study and a potential future site of biomedical intervention. Negotiating the divergence or tension between emerging scientific and regulatory classifications also activated “values levers” and opened up reflective discussions of how classifications embody values and how these values might differ across domains. These data suggest that scholars at the intersections of science and technology studies, ethics, and policy could leverage such openings to identify and intervene in the ways that ethical/regulatory and scientific/technical practices are coproduced within unfolding research. (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Criteria assessment and expert elicitation are combined with existing literature, case law, and regulations in an integrative historical case studies approach. We then use our findings as a tool to explore possibilities for effective oversight and regulatory mechanisms for nanobiotechnology. Section I (...) describes oversight mechanisms for human drugs and medical devices and presents current nanotechnology products. Section II describes the results of expert elicitation research. Section III highlights key criteria and relates them to the literature and larger debate. We conclude with broad lessons for the oversight of nanobiotechnology informed by Sections I-III in order to provide useful analysis from multiple disciplines and perspectives to guide discussions regarding appropriate FDA oversight. (shrink)

This article evaluates the oversight of drugs and medical devices by the U.S. Food and Drug Administration using an integration of public policy, law, and bioethics approaches and employing multiple assessment criteria, including economic, social, safety, and technological. Throughout, assessments employing both the multiple criteria and a method of expert elicitation are combined with the existing literature, case law, and regulations providing an integrative historical case study approach. The goal is to provide useful information from multiple disciplines and perspectives (...) to guide discussions regarding appropriate oversight frameworks for nanobiotechnology applications under the FDA’s purview. (shrink)

The US Food and Drug Administration’s controversial decision to grant accelerated approval to aducanumab (Aduhelm), a therapy for Alzheimer’s disease, has motivated multiple policy reforms. Drawing a case series of other drugs granted accelerated approval and interviews of senior FDA officials, I argue that reform should be informed but not defined by aducanumab. Rather, structural reforms are needed to reshape FDA’s core priorities and restore the regulatory system’s commitment to scientific rigor.

In “Missing the Forest for the Trees: Aduhelm, Accelerated Approvals & the Agency,” Dr. Matthew Herder argues that agency capture and politicized discretion drive delays in confirmatory trials of accelerated approval drugs amongst other concerns at US Food and Drug Administration (FDA). In highlighting this important problem and offering nuanced insight into agency workings based in part on interviews with twenty-three unnamed FDA officials and a three-drug case study, Dr. Herder suggests two innovative solutions. However, amidst broader debates balancing agency (...) expertise, data, and delegation, these proposed policy solutions would benefit from more corroborative evidence and consideration of institutional advantages within constitutional limits. (shrink)

As nanotechnology emerges as an important public policy issue, the FDA's relationship with society is about to be tested. Most would agree that fostering public input will be critical to developing effective public policy for nanotechnology. Yet, it will not be easy. Low public confidence in the FDA, the general lack of knowledge about nanotechnology among ordinary Americans, and the way in which the “average” citizen obtains and evaluates knowledge about a public policy issue all pose serious (...) challenges to any public outreach by the FDA. It will be necessary for the FDA to be attentive to not only its own public messages, but also to who is listening and how those messages are being perceived. (shrink)

In April 2021, the U.S. Food and Drug Administration announced its intention to ban menthol flavoring in cigarettes and cigars. The Agency’s decision was based in part on the disproportionate impact of menthol flavoring in Black communities.

In this article, the authors explore the impact of a potential future regulatory decision by FDA whether or not to continue its enforcement discretion policy allowing physicians to perform, and stool banks to sell, stool product for fecal microbiota transplantation as a treatment for recurrent Clostridium Difficile infection without an Investigative New Drug application. The paper looks at the Agency's regulatory options in light of the current gut microbiota based products that are in the FDA pipeline for drug approval (...) and the potential impact and repercussions of their approval on FDA action. In laying out FDA's options we consider the implications of market exclusivity and off-label use of newly approved drugs. Ultimately, we explore the potential impact of FDA's decision on patients, research, and innovation. (shrink)

There are not many public health issues where views are as extremely polarized as those concerning vaccination policies. Ever since its Fast Track approval by the U.S. Food and Drug Administration in 2006, Merck's human papilloma virus vaccine Gardasil has been sparking controversy. Initially, the criticism has been focused at Merck, due to their overly aggressive marketing strategies and lobbying campaigns. According to a 2007 editorial in Nature Biotechnology, Surrounded by a chorus of disapproval, Merck cracked. As Nature Biotechnology went (...) to press, the company announced a cessation of all efforts to lobby for US state laws requiring compulsory vaccination. Subsequently, questions have been raised whether it was appropriate for vaccine manufacturers to partake in public health policies when their conflicts of interests were so obvious. Some of their advertising campaign slogans, such as cervical cancer kills x women per year and your daughter could become one less life affected by cervical cancer, seemed more designed to promote fear rather than evidence-based decision making about the potential benefits of the vaccine versus any risks. (shrink)

Although the Federal Common Rule requires that informed consent documents include all material information, it does not specify the content of materials used to recruit human subjects. In particular, there is no federal regulation relating to how payment for research participation is to be advertised. Rather, the FDA has issued guidance, advising researchers not to emphasize payment information. In order to determine how IRBs have interpreted this guidance, we coded the policies of the top 100 institutions by receipt of NIH (...) funding, in order to determine whether they require, permit, or forbid researchers to disclose the amount of compensation in their recruitment materials. We found that the vast majority of institutions implicitly or explicitly permit such disclosures; however, there are a significant number of IRBs at each extreme, some discouraging or forbidding with others encouraging or mandating such disclosures. Such heterogeneity in local regulations suggests that IRB discretion may be imposing costs on human subjects and the scientific enterprise that outweigh the benefits. We suggest that this heterogeneity should be resolved towards a national consensus on permissibility. (shrink)

The Food and Drug Administration and the European Medicines Agency have launched a recent initiative to enhance collaboration in research, with the intent to “ensure that clinical trials submitted in drug marketing applications in the United States and European Union are conducted uniformly, appropriately, and ethically.” This initiative recalls efforts from two decades ago when the United States, the European Union and Japan formed the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use as a (...) mechanism for harmonizing clinical research regulations. The intent of harmonization was to improve patients’ “access to new drugs, to prevent unnecessary global development delays and to avoid animal and human study duplications” through policy reconciliation.FDA/EMA efforts at collaboration call for a reassessment of past harmonization efforts: to what extent are ICH member policies already synchronized and to what extent can they be harmonized in the future? This paper will focus on these questions through the lens of pediatric investigation. (shrink)

Delivering high quality genomics-informed care to patients requires accurate test results whose clinical implications are understood. While other actors, including state agencies, professional organizations, and clinicians, are involved, this article focuses on the extent to which the federal agencies that play the most prominent roles — the Centers for Medicare and Medicaid Services enforcing CLIA and the FDA — effectively ensure that these elements are met and concludes by suggesting possible ways to improve their oversight of genomic testing.

The payment of human subjects is an area where Institutional Review Boards have wide discretion. Although the “Common Rule” requires the provision of full information to human research participants to secure valid consent, the Rule is silent on the issue of payment. Still, some federal agencies offer guidance on the matter. For example, the National Science Foundation cautions that high payments for risky research “may induce a needy participant to take a risk that they normally would prefer not to take.” (...) For research under its purview, the Food and Drug Administration guidance provides that “[a]dvertisements may state that subjects will be paid, but should not emphasize the payment or the amount to be paid, by such means as larger or bold type.” One might read the FDA guidance to permit the advertisement for human subjects to state the specific amount of payment, as long as it is not emphasized. (shrink)

In bioethics, the predominant categorization of various types of influence has been a tripartite classification of rational persuasion (meaning influence by reason and argument), coercion (meaning influence by irresistible threats—or on a few accounts, offers), and manipulation (meaning everything in between). The standard ethical analysis in bioethics has been that rational persuasion is always permissible, and coercion is almost always impermissible save a few cases such as imminent threat to self or others. However, many forms of influence fall into the (...) broad middle terrain—and this terrain is in desperate need of conceptual refining and ethical analysis in light of recent interest in using principles from behavioral science to influence health decisions and behaviors. This paper aims to address the neglected space between rational persuasion and coercion in bioethics. First, I argue for conceptual revisions that include removing the “manipulation” label and relabeling this space “nonargumentative]influence,” with two subtypes: “reason-bypassing” and “reason-countering.” Second, I argue that bioethicists have made the mistake of relying heavily on the conceptual categories themselves for normative work and instead should assess the ethical permissibility of a particular instance of influence by asking several key ethical questions, which I elucidate, that relate to (1) the impact of the form of influence on autonomy and (2) the relationship between the influencer and the influenced. Finally, I apply my analysis to two examples of nonargumentative influence in health care and health policy: (1) governmental agencies such as the Food and Drug Administration (FDA) trying to influence the public to be healthier using nonargumentative measures such as vivid images on cigarette packages to make more salient the negative effects of smoking, and (2) a physician framing a surgery in terms of survival rates instead of mortality rates to influence her patient to consent to the surgery. (shrink)

Mobile devices with health apps, direct-to-consumer genetic testing, crowd-sourced information, and other data sources have enabled research by new classes of researchers. Independent researchers, citizen scientists, patient-directed researchers, self-experimenters, and others are not covered by federal research regulations because they are not recipients of federal financial assistance or conducting research in anticipation of a submission to the FDA for approval of a new drug or medical device. This article addresses the difficult policy challenge of promoting the welfare and interests (...) of research participants, as well as the public, in the absence of regulatory requirements and without discouraging independent, innovative scientific inquiry. The article recommends a series of measures, including education, consultation, transparency, self-governance, and regulation to strike the appropriate balance. (shrink)

Armed with expanded federal funding for human embryonic stem cell research and new methods for deriving pluripotent stem cells, stem cell researchers in the U.S. are poised to proceed with unprecedented speed toward the development of new clinical therapies. Staring into the new dawn of regenerative medicine, many observers may assume that the only responsible route to the clinic, both scientifically and ethically, is through FDA-approved clinical trials processes. Conventional wisdom dictates that, like pharmaceutical drugs and the use of biological (...) therapeutics, stem cell-based therapies will have to pass through a series of controlled studies — initially to assess safety and toxicity, then efficacy and comparative efficacy — before they can be justifiably administered to patients outside a clinical trials context. (shrink)

This paper discusses exceptional circumstances under which patients outside of clinical trials are likely to receive innovative stem cell-based interventions. These circumstances involve: (1) stem cell interventions not initially amenable to a clinical trials approach; (2) expanded access to investigational stem cell products (“compassionate use”); and (3) off-label uses of FDA approved stem cell products. This paper proposes a new approach to regulating these exceptional cases.

Smoking remains the leading cause of preventable disease and death in the United States, killing approximately 480,000 people each year. This crushing health burden falls disproportionately, and recent CDC data shows that large disparities in adult cigarette smoking remain. One factor in these disparities is the use of flavors. Menthol cigarettes and other flavored tobacco products are used at higher rates by vulnerable populations including youth and young adults, African Americans, women, Hispanics and Asian Americans. This is no accident; the (...) tobacco industry has long targeted these same groups. Given FDA's failure to act to ban flavored tobacco products, states and municipalities are considering taking matters into their own hands to protect their communities from these dangerous products. The authors will explore state and local authority to restrict the sales of these products and review the evidence base indicating that removing flavored tobacco products – and menthol combustible products in particular - from the market would significantly reduce the toll of illness and death caused by these products. (shrink)

The lead article in the Hastings Center Report's November‐December 2020 issue reconsiders the rationale for requiring that patients have a prescription from a physician to obtain a drug. Madison Kilbride, Steve Joffe, and Holly Fernandez Lynch conclude that growing respect for patient autonomy should lead to a new default for drug access: drugs should be available over the counter unless there are special concerns about harms to third parties or about patients' ability to make decisions for themselves. This conclusion would (...) be a substantial reorientation of drug policy in the United States. Bioethics at a societal level is a theme in the second article, “The Social Risks of Science,” and throughout the issue. (shrink)

This book approaches the problems and circumstances confronting blacks in the context of black values, the black community, and the role of government. ^BContents:: The Black Community's Values as a Basis for Action; The Community as Agent of Change; and The Government's Role in Meeting New Challenges.

Public policy tries to promote appropriate drug use by allowing firms to market drugs in interstate commerce only for uses that the Food and Drug Administration has found to be safe and effective. Because of their medical knowledge, physicians are authorized to prescribe drugs even for uses unapproved by the FDA. Nevertheless, physicians have relied on drug firms for information on appropriate prescribing despite the inherent tension between drug firm dissemination of information to promote sales and rational prescribing. In (...) the past, physicians often relied particularly on drug firm advertising for information on drug use. Today, physicians rely on drug firms to finance continuing medical education. A historical review reveals connections between these two different ways commercial interests have influenced the information that physicians receive and points the way to needed reforms. (shrink)

In 2015, the FDA revised its indefinite deferral policy towards MSM blood donors. I develop an empirical case for the revised policy and show why rights-based objections fail. I introduce and defend a distinction between “ordinary” and “exact” justification that accounts for the worries in the empirical case. I conclude that the FDA is committed to further revising the policy to let MSM donors with exact justification donate.

BackgroundThe U.S. Food and Drug Administration traditionally has kept confidential significant amounts of information relevant to the approval or non-approval of specific drugs, devices, and biologics and about the regulatory status of such medical products in FDA’s pipeline.ObjectiveTo develop practical recommendations for FDA to improve its transparency to the public that FDA could implement by rulemaking or other regulatory processes without further congressional authorization. These recommendations would build on the work of FDA’s Transparency Task Force in 2010.MethodsIn 2016-2017, we convened (...) a team of academic faculty from Harvard Medical School, Brigham and Women’s Hospital, Yale Medical School, Yale Law School, and Johns Hopkins Bloomberg School of Public Health to develop recommendations through an iterative process of reviewing FDA’s practices, considering the legal and policy constraints on FDA in expanding transparency, and obtaining insights from independent observers of FDA.ResultsThe team developed 18 specific recommendations for improving FDA’s transparency to the public. FDA could adopt all these recommendations without further congressional action.FundingThe development of the Blueprint for Transparency at the U.S. Food and Drug Administration was funded by the Laura and John Arnold Foundation. (shrink)

Although tissue plasminogen activator (tPA) is the only medication approved by the United States Food and Drug Administration (FDA) for acute ischemic stroke, there is no consensus about the need for informed consent for its use. As a result, hospitals throughout the U.S. have varying requirements regarding obtaining informed consent from patients for the use of tPA, ranging from no requirement for informed consent to a requirement for verbal or written informed consent. We conducted a study to (1) determine current (...) beliefs about obtaining patients’ informed consent for tPA among a large group of stroke clinicians and (2) identify the ethical, clinical, and organizational factors that influence tPA consent practices. Semi-structured interviews were conducted by trained and experienced investigators and research staff to identify key barriers to implementing acute stroke services. Part of the interview explored current beliefs and practices around informed consent for tPA.This was a multicenter study that included 38 Veterans Health Administration (VHA) hospital locations. Participants were 68 stroke team clinicians, serving primarily on the neurology (35 percent) or emergency medicine (41 percent) service. We conducted thematic analysis based on principles of grounded theory to identify codes about consent for tPA. We used interpretive convergence to ensure consistency among the individual investigators’ codes and to ensure that all of the investigators agreed on coding and themes.We found that 38 percent of the stroke clinicians did not believe any form of consent was necessary for tPA, 47 percent thought that some form of consent was necessary, and 15 percent were unsure. Clinicians who believed tPA required informed consent were divided on whether consent should be written (40 percent) or verbal (60 percent). We identified three factors describing clinicians’ attitudes about consent: (1) legal and policy factors, (2) ethical factors, and (3) medical factors.The lack of consensus regarding consent for tPA creates the potential for delays in treatment, uneasiness among clinicians, and legal liability. The identified factors provide a potential framework to guide discussions about developing a standard of care for acquiring the informed consent of patients for the administration of tPA. (shrink)

The primary responsibility of the US Food and Drug Administration is to protect public health by ensuring the safety of the food supply. To that end, it sometimes conducts risk assessments of novel food products, such as genetically modified food. The FDA describes its regulatory review of GM food as a purely scientific activity, untainted by any normative considerations. This paper provides evidence that the regulatory agency is not justified in making that claim. It is argued that the FDA’s (...) class='Hi'>policy stance on GM food is shaped by neoliberal considerations. The agency’s review of a genetically engineered animal, the AquAdvantage salmon, is used as a case study to track the influence of neoliberalism on its regulatory review protocol. After that, an epistemic argument justifying public engagement in the risk assessment of new GM food is outlined. It is because risk evaluations involve normative judgments, in a democracy, layperson representatives of informal epistemic communities that could be affected by a new GM food should have the opportunity to decide the ethical, political or other normative questions that arise during the regulatory review of that entity. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Women and Health Research:A Report from the Institute of MedicineAnna C. Mastroianni (bio), Ruth Faden (bio), and Daniel Federman (bio)In recent years, claims have been made by segments of the research community and by women's health advocacy groups that clinical research practices and policies have not benefitted women's health to the same extent as men's health. Central to these claims has been an assertion that women have been inadequately (...) represented as subjects of clinical studies and that as a result neither health conditions unique to women—e.g., menopause—nor women's manifestations of health problems affecting both sexes—e.g., heart disease—have been investigated sufficiently.The scientific community, including federal agencies that sponsor and regulate clinical studies, is increasingly responsive to these claims and is taking steps to raise the level of women's participation in clinical studies. Controversy and concern have surrounded these actions, however. Two of the claims that have been made are: (1) that women are more difficult to study than men because of their cyclical hormonal changes; and (2) that conducting gender-specific subgroup analyses would increase the size of study populations, raise the cost of studies, and thereby reduce the number of studies that could be performed with the limited resources available. In addition, controversy over the inclusion of women of childbearing potential and pregnant women has been particularly salient. Concerns have been expressed about avoiding potential harm to existing or potential fetuses and about the possible legal and financial ramifications of such harm. A further concern involves the perceived difficulties in enrolling women in studies and retaining them for the duration of the studies.Against this backdrop, the Office of Research on Women's Health at the National Institutes of Health (NIH) asked the Institute of Medicine (IOM) in October 1992 to establish the Committee on the Ethical and Legal Issues Relating to the Inclusion of Women in Clinical Studies. The Committee's charge was to: (1) consider the ethical and legal implications of including women, particularly pregnant women and women of childbearing potential, in clinical studies; (2) examine known instances of litigation regarding injuries to research subjects [End Page 55] and describe existing legal liabilities and protections; and (3) provide practical advice on these issues for consideration by NIH, institutional review boards (IRBs), and clinical investigators.The 16 Committee members came from diverse backgrounds: bioethics, law, epidemiology and biostatistics, public health policy, obstetrics and gynecology, clinical research, pharmaceutical development, social and behavioral sciences, and clinical evaluative sciences.1 Chaired by two of the authors of this article, Ruth Faden and Daniel Federman, and coordinated by the third, IOM Study Director Anna Mastroianni, the Committee met five times over a fourteen-month period, convened a one-and-one-half day invitational workshop, and commissioned several background papers. The Committee's deliberations were complicated by the announcement of new federal policies late in its term. Specifically, the Food and Drug Administration (FDA) issued guidelines (FDA 1993) to replace its 1977 guidelines, which prohibited the inclusion of women of childbearing potential in early phases of most clinical drug trials. In addition, Congress passed the NIH Revitalization Act of 1993 (P.L. 103-43), which contains provisions mandating the inclusion of women and racial and ethnic minorities in NIH-sponsored clinical research. In February 1994, the IOM Committee publicly issued its final report and recommendations, Women and Health Research: Ethical and Legal Issues of Including Women in Clinical Studies, publishing the workshop presentations and commissioned papers in a separate volume.Deliberations of the CommitteeA number of issues arose at the outset as the Committee considered its charge. A few members initially believed that verification of the underrepresentation of women relative to men in clinical studies as a whole was a prerequisite to providing policy recommendations. Others believed that such an examination would be an important contribution to the knowledge base, but that it was not necessary for addressing the Committee's charge. As summarized in the Committee's report, the Committee's research indicated that firm conclusions about the relative underrepresentation of women could not be drawn from the available data because of the lack of systematic information... (shrink)

Introduction In 2013, Dr. J. Muizelaar and Dr. R. Schrot, two neurosurgeons at the University of California Davis Medical Center (UCDMC), were found guilty of research misconduct due to failure to comply with institutional policies as well as Food and Drug Administration (FDA) regulations governing human subjects research. At issue here, however, is the difference between research and innovative therapy in the clinical setting of patient care where clinical judgment is reasonably to be privileged. Methods The UCDMC investigative document is (...) reviewed along with standard literature on clinical ethics and clinical data about glioblastoma multiforme (GBM) cancer. Results In this paper I argue that, by tendentiously focusing on policies, regulations, and procedures governing human subjects research, the UCDMC investigation failed to account for the centrality of clinical judgment and clinical ethics pertinent to judicious review of this matter, especially given the unique clinical context of terminally ill patients having exhausted standard care treatment options for glioblastoma multiforme (GBM) cancer. Conclusions The UCDMC investigation raises serious problems for clinicians who are engaged in innovative therapy in the clinical setting, requiring a regulatory framework separate from the normal Institutional Review Board (IRB) process. (shrink)

Patients have received experimental pharmaceuticals outside of clinical trials for decades. There are no industry-wide best practices, and many companies that have granted compassionate use, or ‘preapproval’, access to their investigational products have done so without fanfare and without divulging the process or grounds on which decisions were made. The number of compassionate use requests has increased over time. Driving the demand are new treatments for serious unmet medical needs; patient advocacy groups pressing for access to emerging treatments; internet platforms (...) enabling broad awareness of compelling cases or novel drugs and a lack of trust among some that the pharmaceutical industry and/or the FDA have patients’ best interests in mind. High-profile cases in the media have highlighted the gap between patient expectations for compassionate use and company utilisation of fair processes to adjudicate requests. With many pharmaceutical manufacturers, patient groups, healthcare providers and policy analysts unhappy with the inequities of the status quo, fairer and more ethical management of compassionate use requests was needed. This paper reports on a novel collaboration between a pharmaceutical company and an academic medical ethics department that led to the formation of the Compassionate Use Advisory Committee. Comprising medical experts, bioethicists and patient representatives, CompAC established an ethical framework for the allocation of a scarce investigational oncology agent to single patients requesting non-trial access. This is the first account of how the committee was formed and how it built an ethical framework and put it into practice. (shrink)

This compact and innovative book tackles one of the central issues in drug policy: the lack of a coherent conceptual structure for thinking about drugs. Drugs generally fall into one of seven categories: prescription, over the counter, alternative medicine, common-use drugs like alcohol, tobacco and caffeine; religious-use, sports enhancement; and of course illegal street drugs like cocaine and marijuana. Our thinking and policies varies wildly from one to the other, with inconsistencies that derive more from cultural and social values (...) than from medical or scientific facts. Penalties exist for steroid use, while herbal remedies or cold medication are legal. Native Americans may legally use peyote, but others may not. Penalties may vary for using different forms of the same drug, such as crack vs. powder cocaine. Herbal remedies are unregulated by the FDA; but medical marijuana is illegal in most states. Battin and her contributors lay a foundation for a wiser drug policy by promoting consistency and coherency in the discussion of drug issues and by encouraging a unique dialogue across disciplines. The contributors are an interdisciplinary group of scholars mostly based at the University of Utah, and include a pharmacologist, a psychiatrist, a toxicologist, a trial court judge, a law professor, an attorney, a diatary specialist, a physician, a health expert on substance abuse, and Battin herself who is a philosopher. They consider questions like the historical development of current policy and the rationales for it; scientific views on how drugs actually cause harm; how to define the key notions of harm and addiction; and ways in which drug policy can be made more consistent. They conclude with an examination of the implications of a consistent policy for various disciplines and society generally. The book is written accessibly with little need for expert knowledge, and will appeal to a diverse audience of philosophers, bioethicists, clinicians, policy makers, law enforcement, legal scholars and practitioners, social workers, and general readers, as well as to students in areas like pharmacy, medicine, law, nursing, sociology, social work, psychology, and bioethics. (shrink)

Although there is no federal legislation yet on e-cigarettes, the U.S. Food and Drug Administration proposed regulations in April 2014 that would prohibit sales of e-cigarettes to anyone under eighteen and require that they be approved by the FDA as a tobacco product and carry warning labels for consumers on their packaging. Only three U.S. states have extended the same restrictions placed on tobacco products to e-cigarettes; however, eighteen states have passed legislation enacting use restrictions on venues such as schools, (...) state property, or workplaces. Until there is applicable legislation at the federal, state, or municipal levels, health care organizations will have to develop institutional policies if they wish to consistently address the use of e-cigarettes by patients and visitors on their property. (shrink)

Federal efforts beginning in the 1990's have successfully increased pediatric research to improve medical care for all children. Since 1997, the FDA has requested 800 pediatric studies involving 45,000 children. Much of this research is "non-beneficial"; that is, it exposes pediatric subjects to risk even though these children will not benefit from participating in the research. Non-beneficial pediatric research (NBPR) seems, by definition, contrary to the best interests of pediatric subjects, which is why one state supreme court has essentially prohibited (...) it. It also appears that the only plausible rationale for this research is utilitarian, as it risks some children for the good of all. But that rationale is troubling. This Article answers two related questions: (1) What is the appropriate legal relationship between NBPR and the "best interests of the child" standard? (2) What is the ethical justification for this research? I argue that courts should hold that the "best interests" standard governs pediatric research. But, contrary to existing case law, courts must consider the benefits to each child, including pediatric subjects, from a policy that permits NBPR, and not simply consider that a non-beneficial protocol presents more risk than potential benefit to a child. Moreover, I argue that the justification for the practice need not be utilitarian. There is no need to appeal to the greater good to justify the research because each child has reason to endorse a policy permitting NBPR where there is a very low ceiling on acceptable risk, and each child has reason to participate in a practice from which she benefits. More controversially, I argue that each child, like other persons, has reason to help others when she can do so at little to no cost to herself. The Article then highlights practical implications of the offered justifications. (shrink)

This paper examines the culture, the dynamics and the financial underpinnings that determine how medical research is being conducted on children in the United States. Children have increasingly become the subject of experiments that offer them no potential direct benefit but expose them to risks of harm and pain. A wide range of such experiments will be examined, including a lethal heartburn drug test, the experimental insertion of a pacemaker, an invasive insulin infusion experiment, and a fenfluramine "violence prediction" experiment. (...) Emphasis, however, is given to psychoactive drug tests because of the inherent ethical and diagnostic problems involved in the absence of any objective, verifiable diagnostic tool. Effort is made to provide readers comprehensive reference sources to evidence-based reports about the serious risks these drugs pose for adults and children so that the reader may judge whether the benefits (if any) outweigh the risks for children. The first ethical issue raised by these experiments is: did the severity of illness in these children justify their exposure to short and long-term risks? The ethics of the experiments will be evaluated by referring to existing codes of medical research ethics-the Nuremberg Code, the Declaration of Helsinki, and the federal Code of Regulations. The thirteen cases presented will demonstrate that children are being used in ever more speculative experiments, often in the absence of a therapeutic intent, but a significant chance for causing harm and / or discomfort. Some of the experiments were designed to explore the mechanisms of pathology and pharmacological interventions, or the response of neurological brain receptors to chemical provocation ("challenge"). Others were designed to test the safety or efficacy of new drugs, even to test these drugs on healthy children who were hypothesized to be "at risk." Children and adolescents have been subjected to "forced dose titration" experiments that induced a spectrum of severe adverse effects, including insomnia, extreme restlessness, agitation, (akathisia) and self-injurious behavior. FDA reports show that suicide is a significant issue in psychotropic drug trials-in pediatric trials the problem is even greater. The paper aims to demonstrate how the enactment of the Better Pharmaceuticals for Children Act (incorporated into the Food and Drug Administration Modernization Act, FDAMA), set in motion a radical shift in public policy by providing huge financial incentives to pharmaceutical companies to test new or patented drugs in children. Federal policy shifted from one aimed at protecting children by setting limits on permissible research risks, to a policy aimed at broadening the inclusion of children as test subjects. It will be shown how the FDA and the Department of Health and Human Services lifted regulatory restrictions to permit research involving greater than minimal risk to be conducted on healthy children, claiming that all children are potentially "at risk" of a future condition. Children were in this way deprived of regulatory protections. An argument will be made that the approval of nontherapeutic, harmful experiments-such as exposure of toddlers to lead poison-under the current gate keeping system raises serious doubts about the sustainability of institutional review boards (IRBs) as protectors of human research subjects. Children, who are precluded from exercising the adult human's right to informed consent, are being exploited as commodities for commercial ends. It is the position of the author that nothing less than the enactment of a federal law mandating a radical overhaul of the current research review system, with independent checks and balances, will provide children the legal protections they need. Ten specific recommendations are offered to protect children from harmful experiments. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Conflicts—and Consensus—about Conflicts of Interest in MedicineMatthew K. Wynia and Bette–Jane Crigger*This fascinating collection of essays about individual experiences of conflict of interest leaves little doubt that physicians remain divided about the importance, impact and meaning of conflicts of interest in their work. These essays offer differing views about what conflicts of interest look and feel like “on the ground” and about whether specific conflicts of interest are bad, (...) just a fact of life, or maybe even good.Conflict, Conflict EverywhereThese essays situate conflict of interest in a variety of contexts: the treatment recommendations a physician makes for an individual patient; the relationship between teaching physician and medical student or practicing physician and health care organization; the interaction between academic researchers and industry collaborators or professional bodies and industry supporters. In this, the narratives taken together reflect the scope of concern about conflict of interest in medicine familiar in the literature. In his classic 1993 essay, Dennis Thompson noted that concerns about conflict of interest encompass issues of physician self–referral, risk sharing between physicians and health care institutions, gifts from industry, hospital purchasing practices, as well as sponsored research and research with patients (Thompson 1993). To that list have subsequently been added relationships with industry in medical education at all levels, physicians’ service as consultants to industry or members of industry speakers bureau, and development of clinical practice guidelines (Lo & Fields 2009).That almost none of these essays draw attention to some widely publicized situations of conflict of interest—for example, gifts to physicians or the provision of drug samples—should, we think, be seen more as an artifact of the authors’ varied individual experiences than as a failure by the authors to engage key concerns in the ongoing professional and public debate. It could also be that the authors, asked to submit personal stories, assumed that yet another essay about the ‘traditional’ issues in the conflicts of interest literature would be seen as redundant, routine or even boring. Or, there is the tantalizing possibility that the absence of some of the more familiar conflicts from these narratives is the early fruit of efforts to address these traditional issues through policies governing interactions between physicians and industry promulgated by academic medical centers and health systems, medical specialty societies, and industry.One significant area of concern that has emerged in recent years is conflict of interest in the development of clinical practice guidelines. E.g., Choudry et al. 2002; Sniderrman & Furberg 2009; Guyatt et al. 2010. Although none of the essays in this [End Page 101] collection address it head on, Perlmutter touches on several key issues. His depiction of how an FDA committee process limited the input he was able to provide as an expert, undermined his potential to contribute to the professional dialogue, and raised concerns about the objectivity of the drug approval process echoes concerns about objectivity, the role of expert opinion, and the presence on guideline development panels of individuals with financial interests in the recommendations to be developed that have been explored at some length in the literature, most recently by the Institute of Medicine in reports on evidentiary standards (Eden et al 2011) and principles for guideline development (Graham et al. 2011).Conflict of Interest or Dual Agency?Several essays set out physicians’ experience in navigating situations of diverging expectations. Bierut, for example, reflects on the disjunction between the goals and products of academic researchers and commercial sponsors. She saw herself advancing basic knowledge and was forced to grapple with the reality of sponsors’ goals to advance commercial ends as well. Nagldinne and Mikulec each recall struggles to reconcile their obligation to exercise professional judgment on behalf of patients with the demands of health care organizations focussed also on the bottom line. Cruz–Flores attests to the challenge of making recommendations for care when one is both a practicing clinician and a clinical investigator engaged in research that might offer benefit to a patient for whom there are limited options.Thompson defined conflicts of interest as “a set of conditions in which professional judgment concerning a primary interest (such as a patient’s welfare or the validity of... (shrink)

Prescribing drugs for uses that the FDA has not approved — off-label drug use — can sometimes be justified but is typically not supported by substantial evidence of effectiveness. At the root of inappropriate off-label drug use lie perverse incentives for pharmaceutical firms and flawed oversight of prescribing physicians. Typical reform proposals such as increased sanctions for manufacturers might reduce the incidence of unjustified off-label use, but they do not remove the source of the problem. Public policy should address (...) the cause and control the practice. To manage inappropriate off-label drug use, off-label prescriptions must be tracked in order to monitor the risks and benefits and the manufacturers’ conduct. Even more important, reimbursement rules should be changed so that manufacturers cannot profit from off-label sales. When off-label sales pass a critical threshold, manufacturers should also be required to pay for independent testing of the safety and effectiveness of off-label drug uses and for the FDA to review the evidence. Manufacturers should also finance, under FDA supervision, programs designed to warn physicians and the public about the risks of off-label drug use. (shrink)

U.S. Food and Drug Administration policy prohibits blood donation from men who have had sex with men even one time since 1977. Growing moral criticism claims that this policy is discriminatory, a claim rejected by the FDA. An overview of U.S. blood donation, recent donor deferral policy, and the conventional ethical debate introduce the need for a different approach to analyzing discrimination claims. I draw on an institutional understanding of injustice to discern and describe five features of (...) the MSM policy and its FDA context that contribute to its discriminatory effect. I note significant similarities in the 1980s policy of deferring Haitians, suggesting an historical pattern of discrimination in FDA deferral policy. Finally, I point to changes needed to move toward a nondiscriminatory deferral policy. (shrink)

Through expanded access protocols, the Food and Drug Administration (FDA) allows patients with serious or immediately life-threatening diseases access to experimental drugs outside the clinical trial setting when no satisfactory alternative treatment is available. While the FDA has established a mechanism for providing patients with unapproved drug access, the regulations do not require the pharmaceutical company to provide the drug. The drug company’s permission to use its experimental drug is a necessary prerequisite to using the FDA’s expanded access mechanism. Increasingly, (...) drug companies are coming under scrutiny regarding the programs governing that decision-making power. Historically, disclosing whether a company has an expanded access program, and whether or how it would respond to an expanded access request, has been left to discretion of the drug companies themselves. Few manufacturers publish adequate expanded access protocols. As a result, patients were provided with little insight into how companies evaluate expanded access requests and are naturally skeptical as to the ethical integrity of the process. The recently passed 21st Century Cures Act changes that practice by requiring drug companies to have, and make publically available, their expanded access procedures including criteria for evaluating and responding to patient requests. In this article, we contend that complying with the new transparency provisions will require drug companies to respond to several unresolved expanded access issues. Namely, how to reconcile a patient’s desire to access lifesaving experimental therapies alongside the company and society’s interest in the efficient development of new drugs. Even more challenging, how can companies devise practices for evaluating and processing expanded access requests that also fairly and equitably acknowledge those concerns? In addressing these questions, this article explores the legal, regulatory, business, and societal influences that have shaped expanded access policies and practices. From there, we provide companies a framework that balances appropriately the desires of individuals and gaining the requisite approvals ensure access not just for one person but for society. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 10.2 (2000) 171-174 [Access article in PDF] Bioethics Inside the Beltway The Oversight of Human Gene Transfer Research LeRoy Walters Jesse Gelsinger's death last September in a gene transfer study being conducted at the University of Pennsylvania has helped to spark a national debate. In part, this debate parallels the broader discussion of how human subjects research should be reviewed and regulated in the (...) United States. However, human gene transfer research is one of a handful of biomedical technologies that seem to deserve special attention, at least in the early years of their development.The major participants in the national debate on human gene transfer include the National Institutes of Health (NIH), the Food and Drug Administration (FDA), the National Bioethics Advisory Commission, members of Congress, biotechnology and pharmaceutical companies, disease-oriented advocacy groups, reporters, and academics. At the December 1999 meeting of the NIH Recombinant DNA Advisory Committee (RAC), the protocol that involved Jesse Gelsinger was a central focus of discussion, but other topics emerged as well. One ad hoc panel reviewed adverse events that had occurred in other research protocols using adenovirus vectors, while a second proposed changes in the general system for reporting adverse events to NIH and the RAC.During the first several months of the year 2000, the United States Congress also became involved in the human gene transfer debate. In February, Senator Bill Frist (R-TN) convened a hearing to which Jesse Gelsinger's father, representatives of NIH and FDA, and several other witnesses were invited. At approximately the same time, the House Commerce Committee and its Subcommittee on Oversight and Investigations initiated their own inquiries, asking the Office of Inspector General at the Department of Health and Human Services to review the oversight roles of NIH and FDA. In March and April, the House committee also wrote directly to the NIH Director, the FDA Commissioner, and the President of the University of Pennsylvania, requesting extensive documentation on gene transfer, in general, and the trial in which Jesse Gelsinger was involved, in particular. Congressman Henry Waxman (D-CA) and Senator Edward Kennedy (D-MA) have also raised questions and proposed solutions in multiple letters to the NIH Director and the Secretary of Health and Human Services. [End Page 171]The major general questions that have emerged from this discussion are the following:(1) What kinds of information about adverse events should be reported by researchers or sponsors during the course of human gene transfer trials?(2) To what group or groups should adverse-event information be reported? How often and in what ways should the information be analyzed?(3) Should the information about adverse events remain confidential, or should it be discussed publicly?(4) How can the disclosure and consent process in gene transfer trials be improved?(5) Which federal agency should have primary responsibility for overseeing human gene transfer research, and how can it best fulfill its oversight role?How these questions are answered will have immediate relevance to the field of human gene transfer research as it enters into its next phase. At the same time, the models that are created for this important cutting-edge field also may be useful in other complex or controversial arenas of biomedical research, for example, xenotransplantation or human embryonic stem-cell research. In addition, the lessons learned from this one important area of human subjects research may suggest ways to improve protections for all the volunteers who make clinical research--and medical progress--possible.In the remainder of this article, I will turn from reporting, in as objective a way as possible, on the status of the public policy debate about human gene transfer research to suggesting measures for improving the current oversight system for such research. My initial general recommendation is that we should not expect a single regulatory agency to be solely responsible for a field as large and dynamic as human gene transfer research. Rather, there should be some helpful redundancy or, to change the metaphor, checks and balances in the public oversight of this field. Thus, an... (shrink)