Off-label prescribing is an integral part of contemporary medicine. Many patients benefit when they receive drugs or devices under circumstances not specified on the label approved by the Food and Drug Administration. An off-label use may provide the best available intervention for a patient, as well as the standard of care for a particular health problem. In oncology, pediatrics, geriatrics, obstetrics, and other practice areas, patient care could not proceed without off-label prescribing. When scientific and medical (...) evidence justify off-label uses, physicians promote patients’ interests by prescribing products off label.Off-label prescribing can also harm patients, however. The potential for harm is greatest when an offlabel use lacks a solid evidentiary basis. A 2006 study examining prescribing practices for 169 commonly prescribed drugs found high rates of off-label use with little or no scientific support. Researchers examining off-label use in U.S. children’s hospitals concluded, “[W]e still have incomplete knowledge about the safety and efficacy of many medications commonly used to treat children across a range of drug classes and clinical diagnoses.”. (shrink)

Can Covid-19 vaccines be used off-label? Should they be? These were questions on the minds of parents, pediatricians, and the media when the FDA fully approved the Pfizer-BioNTech Covid-19 vaccine for people aged 16 and up. Yet the American Academy of Pediatrics cautioned against pediatric off-label use of the vaccine, and the CDC Covid-19 Vaccine Provider Agreement appears to prohibit it. After briefly contextualizing ethical and legal precedents regarding off-label use, we offer an analysis of the ethical (...) permissibility of and considerations for pediatric off-label Covid-19 vaccination based on individual benefits, risks, and available alternatives. Our analysis challenges the ethics of a blanket prohibition on off-label pediatric Covid-19 vaccination, as it limits clinician ability to provide care they may determine to be clinically and ethically appropriate. At the same time, our analysis acknowledges that Covid-19 creates population-level ethical considerations that are at times in tension with individual health interests. (shrink)

Under current U.S. law, physicians may prescribe drugs and devices in situations not covered on the label approved by the Food and Drug Administration. Those supporting this system say that requiring FDA approval for off-label uses would unnecessarily impede the delivery of benefits to patients. Patients do benefit from off-label prescribing that is supported by sound scientific and medical evidence. In the absence of such evidence, however, off-label prescribing can expose patients to risky and ineffective treatments. (...) The medical community and federal authorities should more actively promote patients' interests in receiving beneficial off-label treatments. To exercise responsible self-regulation, members of the medical community must determine whether available evidence justifies specific off-label uses and must promote information-gathering when the evidence is inadequate. Physicians should also discuss with patients the uncertainties accompanying off-label uses. Federal authorities should more closely monitor the effects of off-label prescribing and adopt other measures to reduce harm and enhance benefits produced by off-label prescribing. (shrink)

The term “off-label drug use” refers to drugs that have not yet acquired “approved” status or drugs that have acquired “approved” status but are used with a different dosage, route, or administration method other than that for which the drug has been approved. In New Zealand, the Medicines Act 1981 specifically allows for off-label drug use. However, this authority is limited by the Health and Disability Commissioner Regulations 1996 and the common law, which require that off-label drug (...) use is of an acceptable standard, that the patient should be fully informed, and that the patient should give informed consent. Off-label drug use is an important issue because the current law provides medical practitioners very wide discretionary power, without providing clarification for what is required of the practitioner in exercising his or her discretion in prescribing off-label. This paper discusses possible solutions to this issue, for example, establishing protocol for off-label use, an electronic database of off-label use, and the amendment of legal provisions. (shrink)

We argue that the universal recommendations against “off-label” pediatric use of approved COVID-19 issued by the FDA, CDC, and AAP are overbroad. Especially for higher-risk children, vaccination can be ethically justified even before FDA authorization or approval – and similar reasoning is relevant for even younger patients. Legal risks can also be managed, although the FDA, CDC, and Department of Health and Human Services (HHS) should move quickly to provide clarity.

Anti-vascular endothelial growth factor therapy has revolutionised the treatment of a variety of ophthalmic conditions and has become the first-line therapy for a range of retinal diseases. Bevacizumab, a VEGF inhibitor first approved for the treatment of colorectal cancer, has been shown to be nearly or virtually as effective and safe as other anti-VEGF therapies in the treatment of certain retinal diseases but is not approved or registered by the Food and Drug Administration or European Medicines Agency. While other anti-VEGF (...) options are approved and registered, they are generally more expensive and less accessible. Accordingly, despite its off-label status, bevacizumab is frequently used for a variety of disabling retinal diseases. Indeed, bevacizumab is included on the World Health Organization’s list of essential medicines. However, its use in some parts of the world remains restricted due to its off-label status. How, then, should healthcare authorities approach this situation? What are the ethical and societal implications of adhering to a standard and generally effective evaluation and approval system while restricting access to a potentially cost-saving therapy? In countries where its use is not restricted, how should providers approach off-label treatment with bevacizumab? By examining the evidence behind bevacizumab’s efficacy and safety and evaluating the individual and societal implications of off-label use and restriction, this paper illustrates the ethical factors providers and policy makers must consider in the off-label use of bevacizumab and ultimately argues for increased access to bevacizumab in the treatment of retinal disease. (shrink)

Artykuł dotyczy instytucji pozarejestracyjnego stosowania produktów leczniczych oraz problemów w rozgraniczeniu sytuacji, w których taka forma leczenia ma charakter terapii innowacyjnej od normalnej praktyki leczniczej. Poruszona została kwestia istotnego ryzyka kwalifikacji rutynowej terapii przy użyciu produktów leczniczych jako eksperymentu medycznego oraz relacja pomiędzy pojęciem aktualnej wiedzy medycznej a Charakterystyką Produktu Leczniczego. Omówione zostały trudności w ustaleniu, czy proponowany sposób leczenia jest metodą nową lub częściowo wypróbowaną oraz przedstawiono postulat zwiększenia aktywności lekarskich towarzystw naukowych w tym zakresie. Przedstawiono implikacje kwalifikacji leczenia (...) off-label jako eksperymentu leczniczego w zakresie konieczności uzyskania opinii komisji bioetycznej oraz zawarcia ubezpieczenia odpowiedzialności cywilnej podmiotu przeprowadzającego eksperyment medyczny oraz ich wpływ na bezpieczeństwo pacjenta, bezpieczeństwo prawne lekarza oraz dostępność do świadczeń medycznych. (shrink)

BackgroundDepressive disorders are a common form of psychiatric illness and cause significant disability. Regulation authorities, the medical profession and the public require high safety standards for antidepressants to protect vulnerable psychiatric patients. Ketamine is a dissociative anaesthetic and a derivative of a hallucinogen. Its abuse is a major worldwide public health problem. Ketamine is a scheduled drug and its usage is restricted due to its abuse liability. Recent clinical trials have reported that ketamine use led to rapid antidepressant effects in (...) patients suffering from treatment-resistant depression. However, various flaws in study designs, and possible biased reporting of results, may have influenced those findings. Further analyses of ketamine use are needed to ensure patient safety.DiscussionThe use of ketamine in research and treatment of depressive disorders is controversial. Recently, mental health professionals raised ethical concerns about an ongoing ketamine trial in the UK. Also, a Canadian agency reviewed the existing evidence and did not recommend prescribing ketamine to treat depressive disorders. Findings obtained from tightly controlled research settings cannot be easily translated to clinical practice as substance abuse is commonly comorbid with depressive disorders. An effective antidepressant should reduce severity of depressive symptoms without liability problems. Although the US FDA has not approved the use of ketamine to treat depressive disorders, some psychiatrists offer off-label repeat prescription of ketamine. Prescribing ketamine for treating depressive disorders requires substantial empirical evidence. Clinicians should also consider research findings on ketamine abuse. Depressive disorders can be chronic conditions and the current evidence does not rule out the risk of substance abuse after repeat prescription of ketamine. Off-label ketamine use in treating depressive disorders may breach ethical and moral standards, especially in countries seriously affected by ketamine abuse. This article presents two real-world clinical vignettes which highlight ethical principles and theories, including autonomy, nonmaleficience, fidelity and consequentialism, as related to off-label ketamine use.ConclusionWe urge clinicians to minimise the risk of harming patients by considering the empirical evidence on ketamine properties and attempting all standard antidepressant therapies before considering the off-label use of ketamine. (shrink)

In the United States, while it is legal for physicians to prescribe drugs for “off-label” indications (uses for which the drugs do not have Food and Drug Administration approval), it is largely—though not entirely—illegal for drug manufacturers to promote off-label uses of their drugs to physicians. In recent months, the rules against off-label marketing have been rigorously enforced: in October, Allergan reached a $375 million settlement over off-label promotion of Botox; in September, Novartis settled an off- (...) class='Hi'>label marketing dispute for $422.5 million, and Forest Laboratories settled one for $313 million. These were only the latest in a series of criminal and civil settlements on off-label promotion, the most .. (shrink)

Although there are exceptions, the principle of primum nil nocere remains the cornerstone of the practice of medicine. In the well known handbook, Goodman and Gilman’s The Pharmacological Basis of Therapeutics1 a case is presented which raises doubts about the permissibility of off-label administration of certain drugs to healthy troops as a preventive measure. The following citation from this handbook gives a clear description of the problem:"Prophylaxis in cholinesterase inhibitor poisoning. Studies in experimental animals have shown that pretreatment with (...) pyridostigmine reduces the incapacitation and mortality associated with “nerve agent” poisoning, particularly for agents, such as soman, that … ". (shrink)

Unter Off-Label-Use versteht man den zulassungsüberschreitenden Einsatz eines Arzneimittels außerhalb der von Zulassungsbehörden genehmigten Anwendungsgebiete. Er ist in der medizinischen Praxis weit verbreitet und fächerübergreifend zu beobachten. Der Beitrag gibt eine Einschätzung der Off-Label-Anwendung aus ethischer Sicht. Dazu wird die Off- Label-Anwendung zunächst von anderen, sachlich verwandten Anwendungsweisen abgegrenzt. Danach wird über die aktuelle Verbreitung des Off-Label- Use informiert. Sodann wird gezeigt, dass sich bekannte Problemlagen aus der Medizinethik bei der Off-Label-Anwendung in spezifischer Weise verschärfen. (...) Schließlich wird diskutiert, wie eine ethisch akzeptable Off-Label-Anwendung von Arzneimitteln ausgestaltet werden könnte und auf welchen Ebenen sie ansetzen müsste. (shrink)

The Food and Drug Administration authorizes the marketing of a drug only for uses that the manufacturer has demonstrated to be safe and effective, based on evidence from at least two clinical trials. However, the FDA does not regulate the practice of medicine, so physicians may prescribe drugs in any manner they choose. Prescribing drugs in ways that deviate from the uses specified in the FDA-approved drug label, package insert, and marketing authorization is referred to as off-label prescribing. (...) This occurs when physicians prescribe a drug for a therapeutic purpose other than the one approved by the FDA; treat patients in a different age cohort or gender than the population on which it was tested; or prescribe a different dose, for a different duration of use, or a different mode of administration than indicated on the label. (shrink)

We wish to point out an additional consequence of the Catch-22 described by Andreae and colleagues (Andreae et al. 2016). The decades-long research gridlock of controlled drugs has unintentionally...

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)

Volume 19, Issue 6, June 2019, Page 22-25.

Coronavirus disease 2019 is a fast-developing viral pandemic spreading across the globe. Due to lack of availability of proven medicines against COVID-19, physicians have resorted to treatments through large trials of investigational drugs with poor evidence or those used for similar diseases. Large trials randomize 100–500+ patients at multiple hospitals in different countries to either receive these drugs or standard treatment. In order to expedite the process, some regulatory agencies had also given permission to use drugs approved for other diseases, (...) despite a lack of evidence of efficacy in COVID-19. In this review, we highlight the potential ethical issues that should be addressed during the use of investigational drugs with little prior evidence as a treatment options during a pandemic. We discuss the impact of design of randomized clinical trials using LOTUS trial as an example and that of off-label use of drugs like chloroquine/hydroxychloroquine on the safety of patients during COVID-19. We conclude that the adaptive randomized clinical trial designs offer a flexible and efficient approach, enabling patients to quickly switch to successful treatments, while minimizing the number of patients on standard of care. Randomized clinical trial design should consider blinding of investigators and only representative patients who can provide consent should be included. We also conclude the emergency approvals of drugs should be carefully issued and off-label use should be restricted in pandemics. Streamlined regulatory guidelines for emergency drug use in a pandemic can also help in providing benefit and minimizing harm to patients in the future. (shrink)

Previous research conducted in 1999 highlighted ethical concerns behind challenge studies inducing psychosis with ketamine and made recommendations to enhance ethical standards. Recently, a plethora of clinical trials have evaluated the efficacy of ketamine to treat mood disorders, which lead to complex ethical issues. Pharmaceutical companies and researchers hope to profit by developing patentable variations on ketamine for treating depression. Media have labeled ketamine as a “miracle” antidepressant. Some clinics offer expensive off-label use of ketamine to treat mood disorders. (...) This article examines the ecological validity of ketamine trials, measures to protect patients, informed consent procedures, financial inducements to participants and conflict of interest of researchers, therapeutic misconception, concealment, and deception. Further recommendations are purposed to improve ethical standard of clinical research involving ketamine. (shrink)

Last year I described in this journal1 an unacceptable influence of a pharmaceutical company on the off-label use of one of its products. Now I would like to report on an acceptable and even praiseworthy initiative of a pharmaceutical manufacturer in monitoring the use of its drug. The devastating action of thalidomide on the human embryo caused its withdrawal from the market in ….

People have a love/hate relationship with rapidly changing healthcare technology. While consumer demand for medical apps continues to grow as rapidly as does supply, healthcare professionals and safety experts worry about the impact of these apps on the health consumer. In response to the rapidly growing mobile healthcare sector, the Food and Drug Administration has put forth guidelines to regulate ‘mobile medical apps’, those health-related apps that are designated as medical devices. In this article, I argue that this decision, to (...) only regulate apps that bill themselves as medical devices, will create a market for ‘off-label’ app use. Further, I will talk about the oft used analogy between off-label apps and off-label pharmaceuticals, showing that off-labeling apps will provide patients none of the benefits that come with a physician prescribing a drug off-label, while exposing the mobile healthcare consumer to significant risks that go significantly beyond those that we know of from prescription drugs. Recognizing that the Food and Drug Administration is not going to be able to significantly change its policies on oversight, I will suggest specific actions to at least mitigate some of the risks associated with off-label app use. (shrink)

Gebhardt draws attention to an important issue. The responsibility for informing and warning patients about adverse effects and how to prevent them, or ….

It is generally assumed that the debate between theory‐theory and simulation theory is an empirical one, but this view of the structure of the debate is misleading. It is an a priori truth that theory‐theory is mistaken and equally a priori that simulation in one sense (here labelled ‘co‐cognition’) is central in thinking about the thoughts of others. Given this, it is a further question how our co‐cognitive powers are realized in sub‐personal machinery. Here simulation in quite another sense (that (...) involving such ideas as ‘pretend states’ and ‘off‐line’ mental processes) may provide one possible answer. (shrink)

In this article I offer an account and analysis of several patterns of valuation of the cardinal directions in medieval Scandinavian texts. While my topic is not altogether novel—ideas about space, along with those of time, have been matters of widespread and perennial concern to scholars of culture and religion, and those interested in the Norse context have proven no exception—I seek to go beyond previous examinations in several ways. First, many of the scholars who have focused on directionality in (...) Old Norse sources have been concerned with catalogu-ing and elucidating terminology for the cardinal points and for movement along and between them, with a particular emphasis on assessing the “correctness” of such terms' application in respect to ultimate or relative orientation. While I draw on the insights of such studies, my interests lie less in efforts to map or to describe movement in the real world known to medieval Scandinavians than in the values that they can be shown to have attached to the cardinal directions. My focus, therefore, is on imagined or moral as opposed to physical or topographical space. Of the studies that have taken a similar interest in Norse ideas about space, most have focused mainly or exclusively on the attempt, often from a structuralist perspective, to reconstruct from available sources pagan cosmography, to discover or assemble a systematic summa of the pre-Christian Norse mythical Weltbild. While pre-Christian ideas, or their traces, are also a focus of my article, I pay more than equal attention to conceptualizations and valuations of space held by Christian northerners. “Mythical,” then, is not a label that I reserve for heathen or patently fantastic materials but one under which I also subsume data from Christian and historiographical sources. (shrink)

In this commentary, I explore the ethically relevant dimensions of menu labelling. The evidence that menu labelling changes purchasing or consumption behaviour is contentious and inconclusive; there is some suggestion that menu labelling may preferentially influence the behaviour of healthier and wealthier citizens. Some suggest that menu labelling is unjust, as it fails to direct resources towards those who most need them. An alternative is to see menu labels as just one of a set of strategies that can increase people’s (...) real opportunities to be healthy. Complementing strategies will be necessary to ensure that all citizens can consider and value food choices, which may include becoming a more critical consumer in the food marketplace. Menu labels may also have the potential to shift our attention from people to food, reallocate responsibility in the food environment and facilitate structural change. It would be a mistake to expect too much of menu labels alone: rather, they should be integrated into a broader programme that supports health opportunities, especially for the least well off. (shrink)

Growing supermarket dominance and the expansion of own-label market share in Australia has put considerable pressure on agri-food manufacturers, and the recent movement of a number of manufacturing operations off-shore has attracted widespread attention. This paper examines the pursuit of an international manufacturing base by SPC Ardmona, one of Australia’s major fruit and vegetable processors, with a focus on strategic alliances formed with Siam Foods in Thailand and Rhodes Food Group in South Africa/Swaziland. Strategic horizontal alliances have become increasingly (...) important for manufacturers seeking to counter retailer dominance, yet have received little attention in the agri-food literature. The two alliances examined in this paper illustrate the profound importance of prevailing societal and institutional environments in which production networks ‘touch-down’, and their influence on firm-level dynamics of trust, motivation, corporate values, and strategic objectives. Horizontal alliances can offer a promising alternative to cut-throat competition and a ‘race- to-the-bottom’ between agri-food manufacturers. However, with own-label sourcing strategies deepening competition between geographically-disparate manufacturers, identifying compatible alliance partners is likely to become an increasingly greater challenge. (shrink)

The year 2020 is facing one of the worst public health situations in decades. The world is experiencing a pandemic that has triggered significant challenges to healthcare systems in both high and low‐middle income countries (LMICs). Government policymakers and healthcare personnel are experiencing real‐life ethical dilemmas and are pressed to respond to these situations. Many possible treatments are being investigated, one of which is the use of hydroxychloroquine or chloroquine. These drugs are approved for use by patients with systemic lupus (...) erythematosus (SLE), rheumatoid arthritis, and malaria. The demand for these products has increased, and the stocks are depleting for the patient population for whom the drugs are intended initially. Although both innovator and generic pharmaceutical manufacturers are making plans for increased production, there are challenges with global supply chains disruption and the retention of supplies for local markets. This may cause countries that rely on the importation of pharmaceuticals to be out of stock of supplies for an extended period. There are allegations of off‐label prescribing and hoarding. Pharmacists are the custodians and dispensers of medications and are faced with the task of assessing prescriptions and making decisions about the allocation of these products. This paper seeks to 1) highlight some of the ethical challenges of dispensing hydroxychloroquine by pharmacists during the COVID‐19 pandemic, 2) identify some of the responses to these issues from various regulatory authorities in the USA, and 3) recommend approaches to assist pharmacists in their decision‐making process, especially in LMICs. (shrink)

Artykuł przedstawia rozważania oparte na regulacji prawa unijnego oraz polskiego dotyczące wytwarzania oraz stosowania produktów leczniczych terapii zaawansowanej – wyjątków szpitalnych. Autorka omawia unijne źródło regulacji ATMP-HE, jej funkcję oraz cel wprowadzenia do prawa unijnego, a następnie relację tej regulacji do polskiego uregulowania dotyczącego eksperymentu leczniczego. W ocenie autorki na gruncie obowiązującego stanu prawnego nie jest zasadne stanowisko, zgodnie z którym produkt leczniczy terapii zaawansowanej – wyjątek szpitalny jest na tyle legalnie odrębnym pojęciem, a wręcz instytucją prawną, że nie stosuje (...) się do niego regulacji krajowej. Jest to bowiem stanowisko nie tylko niespójne z regulacją unijną oraz krajową, ale również skutkujące przerzuceniem ciężaru ryzyka zastosowania tego produktu bez jakiejkolwiek kontroli oraz odpowiedzialności na pacjenta. Autorka wyraziła stanowisko, zgodnie z którym de lege lata zastosowanie produktu leczniczego terapii zaawansowanej – wyjątku szpitalnego należy kwalifikować jako eksperyment leczniczy, do którego stosuje się także granice dopuszczalności jego przeprowadzenia. Autorka przedstawia skutki uznania zastosowania ATMP-HE za eksperyment leczniczy oraz skutki przyjęcia stanowiska odmiennego. Ponadto w artykule zawarte zostały rozważania na temat niezasadności utożsamiania stosowania ATMP-HE z off-label use oraz compassionate use. Autorka sformułowała również postulaty de lege ferenda. (shrink)

The year 2020 is facing one of the worst public health situations in decades. The world is experiencing a pandemic that has triggered significant challenges to healthcare systems in both high and low‐middle income countries (LMICs). Government policymakers and healthcare personnel are experiencing real‐life ethical dilemmas and are pressed to respond to these situations. Many possible treatments are being investigated, one of which is the use of hydroxychloroquine or chloroquine. These drugs are approved for use by patients with systemic lupus (...) erythematosus (SLE), rheumatoid arthritis, and malaria. The demand for these products has increased, and the stocks are depleting for the patient population for whom the drugs are intended initially. Although both innovator and generic pharmaceutical manufacturers are making plans for increased production, there are challenges with global supply chains disruption and the retention of supplies for local markets. This may cause countries that rely on the importation of pharmaceuticals to be out of stock of supplies for an extended period. There are allegations of off‐label prescribing and hoarding. Pharmacists are the custodians and dispensers of medications and are faced with the task of assessing prescriptions and making decisions about the allocation of these products. This paper seeks to 1) highlight some of the ethical challenges of dispensing hydroxychloroquine by pharmacists during the COVID‐19 pandemic, 2) identify some of the responses to these issues from various regulatory authorities in the USA, and 3) recommend approaches to assist pharmacists in their decision‐making process, especially in LMICs. (shrink)

Luck egalitarians need to address the question of cost-responsibility: If an individual is responsible for being worse off than others, then what benefits, if any, is that individual uniquely cost-responsible for? By applying luck egalitarianism to justice in health I discuss different answers to this question inspired by two different interpretations of luck egalitarianism, namely ‘standard luck egalitarianism’ and ‘all luck egalitarianism’, respectively. Even though I argue that the latter is more plausible than the former, I ultimately suggest and defend (...) a third interpretation of luck egalitarianism, which I label ‘universal luck egalitarianism’. Finally, I adjust my findings to a (all things considered) more plausible currency, namely welfare. (shrink)

Many drugs have therapeutic off-label uses for which they were not originally designed. Some drugs designed to treat neuropsychiatric and other disorders may enhance certain normal cognitive and affective functions. Because the long-term effects of cognitive and affective enhancement are not known and may be harmful, a precautionary principle limiting its use seems warranted. As an expression of autonomy, though, competent individuals should be permitted to take cognition- and mood-enhancing agents. But they need to be aware of the risks (...) in chronic use of these agents and to take responsibility for their effects. A reasonable middle ground between these positions is to warn those who choose to enhance that doing so entails risks. (shrink)

The hopes and fears expressed in the debate on human enhancement are not always based on a realistic assessment of the expected possibilities. Discussions about extreme scenarios may at times obscure the ethical and policy issues that are relevant today. This paper aims to contribute to an adequate and ethically sound societal response to actual current developments. After a brief outline of the ethical debate concerning neuro-enhancement, it describes the current state of the art in psychopharmacological science and current uses (...) of psychopharmacological enhancement, as well as the prospects for the near future. It then identifies ethical issues regarding psychopharmacological enhancements that require attention from policymakers, both on the professional and on the governmental level. These concern enhancement research, the gradual expansion of medical categories, off-label prescription and responsibility of doctors, and accessibility of enhancers on the Internet. It is concluded that further discussion on the advantages and drawbacks of enhancers on a collective social level is still needed. (shrink)

Neurotherapies for diagnostics and treatment—such as electroencephalography (EEG) neurofeedback, single-photon emission computerized tomography (SPECT) imaging for neuropsychiatric evaluation, and off-label/experimental uses of brain stimulation—are continuously being offered to the public outside mainstream healthcare settings. Because these neurotherapies share many key features of complementary and alternative medicine (CAM) techniques—and meet the definition of CAM as set out in Kaptchuk and Eisenberg—here we refer to them as “alternative neurotherapies.” By explicitly linking these alternative neurotherapy practices under a common conceptual framework, this (...) paper draws attention to, and critically considers, the cross-cutting ethical and legal issues related to the provision of these services. The first section of this paper provides an updated empirical overview of uses of SPECT neuropsychiatric evaluations, EEG neurofeedback, and experimental/off-label forms of brain stimulation. Next, drawing on CAM bioethics scholarship, we highlight the pertinent ethical issues in the alternative neurotherapy context, including the truthful representation of evidence base, marketing to vulnerable populations, potential harms, provider competency, and conflicts of interest. Finally, we consider the principal legal issues at stake for the provision of alternative neurotherapies in the U.S., namely those related to licensing and scope-of-practice considerations. We conclude with recommendations for future research in this domain. (shrink)

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)

Transcranial Magnetic Stimulation (TMS) is a non-invasive neurostimulatory and neuromodulatory technique increasingly used in clinical and research practices around the world. Historically, the ethical considerations guiding the therapeutic practice of TMS were largely concerned with aspects of subject safety in clinical trials. While safety remains of paramount importance, the recent US Food and Drug Administration approval of the Neuronetics NeuroStar TMS device for the treatment of specific medication-resistant depression has raised a number of additional ethical concerns, including marketing, off-label (...) use and technician certification. This article provides an overview of the history of TMS and highlights the ethical questions that are likely arise as the therapeutic use of TMS continues to expand. (shrink)

The hopes and fears expressed in the debate on human enhancement are not always based on a realistic assessment of the expected possibilities. Discussions about extreme scenarios may at times obscure the ethical and policy issues that are relevant today. This paper aims to contribute to an adequate and ethically sound societal response to actual current developments. After a brief outline of the ethical debate concerning neuro-enhancement, it describes the current state of the art in psychopharmacological science and current uses (...) of psychopharmacological enhancement, as well as the prospects for the near future. It then identifies ethical issues regarding psychopharmacological enhancements that require attention from policymakers, both on the professional and on the governmental level. These concern enhancement research, the gradual expansion of medical categories, off-label prescription and responsibility of doctors, and accessibility of enhancers on the Internet. It is concluded that further discussion on the advantages and drawbacks of enhancers on a collective social level is still needed. (shrink)

Yet while all features of reality are dependent upon discourse, are there perhaps some features of discourse that are independent of reality the differences, for example, between the ways two discourses may say exactly the same thing? The old and ugly notion of synonomy rattles a warning here: Can there ever be two different discourses that say exactly the same thing in different ways, or does every difference between discourses make a difference in what is said? Luckily, we can pass (...) over that general question here. We are concerned only with the specific question whether organization into referential chains and levels is purely conventional, independent of everything beyond discourse. And the plain answer is that such organization of discourse participates notably in the organization of a reality. A label in any nonnull application, literal or metaphorical, marks off entities of a certain kind, and even where the denotation is null, the label marks off labels of a certain kind that apply to that label. Just such marking off or selection of entities and relevant kinds makes them such as distinguished from the results of alternative organizations.Nelson Goodman, emeritus professor of philosophy at Harvard University and the author of, among other works, The Structure of Appearance, Ways of Worldmaking, and Problems and Projects, is currently working on projects in the performing arts and on a new collection of essays. His previous contributions to Critical Inquiry are "The Status of Style' , "Metaphor as Moonlighting" , "Twisted Tales; or, Story, Study, and Symphony" , and "The Telling and the Told". (shrink)

Psychotropic and other drugs can alter brain mechanisms regulating the formation, storage, and retrieval of different types of memory. These include “off label” uses of existing drugs and new drugs designed specifically to target the neural bases of memory. This paper discusses the use of beta-adrenergic antagonists to prevent or erase non-conscious pathological emotional memories in the amygdala. It also discusses the use of novel psychopharmacological agents to enhance long term semantic and short term working memory by altering storage (...) and retrieval mechanisms in the hippocampus and prefrontal cortex. Although intervention in the brain to alter memory as therapy or enhancement holds considerable promise, the long term effects of experimental drugs on the brain and memory are not known. More studies are needed to adequately assess the potential benefits and risks of these interventions. (shrink)

Since the onset of the SARS-CoV-2 pandemic, an array of off-label interventions has been used to treat patients, either provided as compassionate care or tested in clinical trials. There is a challenge in determining the justification for conducting randomised controlled trials over providing compassionate use in an emergency setting. A rapid and more accurate evaluation tool is needed to assess the effect of these treatments. Given the similarity to the Ebola Virus Disease (EVD) pandemic in Africa in 2014, we (...) suggest using a tool designed by the WHO committee in the aftermath of the EVD pandemic: Monitored Emergency Use of Unregistered and Investigational Interventions (MEURI). Considering the uncertainty around SARS-CoV-2, we propose using an improved MEURI including the Plan–Do–Study–Act tool. This combined tool may facilitate dynamic monitoring, analysing, re-evaluating and re-authorising emergency use of unproven treatments and repeat it in cycles. It will enable adjustment and application of outcomes to clinical practice according to changing circumstances and increase the production of valuable data to promote the best standard of care and high-quality research—even during a pandemic. (shrink)

There are numerous ways people can improve their cognitive capacities: good nutrition and regular exercise can produce long-term improvements across many cognitive domains, whilst commonplace stimulants such as coffee temporarily boost levels of alertness and concentration. Effects like these have been well-documented in the medical literature and they raise few ethical issues. More recently, however, clinical research has shown that the off-label use of some pharmaceuticals can, under certain conditions, have modest cognition-improving effects. Substances such as methylphenidate and modafinil (...) can improve capacities such as working memory and concentration in some healthy individuals. Unlike their more mundane predecessors, these methods of “cognitive enhancement” are thought to raise a multitude of ethical issues. This paper presents the six principal ethical issues raised in relation to pharmacological cognitive enhancers —issues such as whether: the medical safety-profile of PCEs justifies restricting or permitting their elective or required use; the enhanced mind can be an “authentic” mind; individuals might be coerced into using PCEs;, there is a meaningful distinction to be made between the treatment vs. enhancement effect of the same PCE; unequal access to PCEs would have implications for distributive justice; and PCE use constitutes cheating in competitive contexts. In reviewing the six principal issues, the paper discusses how neuroscientific research might help advance the ethical debate. In particular, the paper presents new arguments about the contribution neuroscience could make to debates about justice, fairness, and cheating, ultimately concluding that neuroscientific research into “personalized enhancement” will be essential if policy is to be truly informed and ethical. We propose an “ethical agenda” for neuroscientific research into PCEs. (shrink)

Providing in-utero treatments to target specific conditions in the fetus is a relatively new approach in perinatal care, with the vast majority of these treatments being used off-label. The high degree of off-label medication use in the perinatal and neonatal settings raises concern for the safety of both the fetuses and expectant mothers. This report presents two examples of intra-amniotic drug administration based on reported clinical cases. From the ethical framework of medical principlism, we examine the competing ethical (...) duties of autonomy, beneficence, and non-maleficence in this setting. We then lay out three fundamental ethical principles for obtaining informed consent and maximizing clinical benefit. (shrink)