Drug regulation is fraught with inductive risk. Regulators must make a prediction about whether or not an experimental pharmaceutical will be effective and relatively safe when used by typical patients, and such predictions are based on a complex, indeterminate, and incomplete evidential basis. Such inductive risk has important practical consequences. If regulators reject an experimental drug when it in fact has a favourable benefit/harm profile, then a valuable intervention is denied to the public and a company’s material (...) interests are needlessly thwarted. Conversely, if regulators approve an experimental drug when it in fact has an unfavourable benefit/harm profile, then resources are wasted, people are needlessly harmed, and other potentially more effective treatments are underutilized. Given that such regulatory decisions have these practical consequences, non-epistemic values about the relative importance of these consequences impact the way such regulatory decisions are made (similar to the analysis of laboratory studies on the toxic effects of dioxins presented in Douglas [2000]). To balance the competing demands of the pertinent non-epistemic values, regulators must perform what I call an “inductive risk calculus.” At least in the American context this inductive risk calculus is not well-managed. (shrink)

The FDA's new table of surrogate endpoints used for drug approvals is an important step forward for overseeing the use of biomarkers in clinical trials. Nevertheless, we present several ways in which the table can be improved.

Efforts to foster transparency in biopharmaceutical regulation are well underway: drug manufacturers are, for example, legally required to register clinical trials and share research results in the United States and Europe. Recently, the policy conversation has shifted toward the disclosure of clinical trial data, not just trial designs and basic results. Here, I argue that clinical trial registration and disclosure of clinical trial data are necessary but insufficient. There is also a need to ensure that regulatory decisions that (...) flow from clinical trials — whether positive (i.e., product approvals) or negative (i.e., abandoned products, product refusals, and withdrawals) — are open to outside scrutiny. Further, a jurisprudence of drug regulation is needed. I develop two arguments motivated by (1) innovation concerns and (2) the value of good governance in support of openly publishing all final decisions for approved, abandoned, refused, and withdrawn products. After articulating why greater transparency in regulatory decision-making is needed, I distil four essential features of a jurisprudence of drug regulation that prescribe policy changes in terms not only of the transparency of regulatory outcomes and the underlying reasoning, but also regulatory organization. (shrink)

Efforts to ensure greater transparency in the regulation of “drugs” are well underway. For example, laws in the United States and Europe now require registration of most clinical trials beyond phase 1. Yet instances of avoidable harm to patients continue to arise. In response, calls for disclosure of clinical trial data in the form of “clinical study reports,” not just trial designs and basic results, are growing. In this paper, I argue that disclosure of clinical trial data is necessary (...) but insufficient. Rather, the regulatory decisions that flow from those trial data —whether positive or negative —should also be open to outside scrutiny provided they are final in nature. (shrink)

Regulators rely on clinical trials for drug approval and labeling decisions. Health systems and clinicians rely on the evidence from trials to determine treatment, and patients rely on it to decide which courses of care to undertake. Many of these stakeholders presume that the careful review of individual studies is enough to address the ethical and scientific questions that arise in clinical trials. In what follows, however, we demonstrate that explicit consideration of trial portfolios—series of trials that are interrelated (...) by a common set of objectives—is crucial. the ethical acceptability and evidentiary probity of individual trials can change depending on the characteristics of the portfolios in which they are embedded. Second, how trial portfolios are composed, how well they are coordinated, and how efficiently they use information determines the balance of risks and benefits they present as well as their different prospects for generating socially valuable information; these three factors also raise distinct questions of justice. (shrink)

Over the last decade, philosophers of science have extensively criticized the epistemic superiority of randomized controlled trials for testing safety and effectiveness of new drugs, defending instead various forms of evidential pluralism. We argue that scientific methods in regulatory decision-making cannot be assessed in epistemic terms only: there are costs involved. Drawing on the legal distinction between rules and standards, we show that drug regulation based on evidential pluralism has much higher costs than our current RCT-based system. We (...) analyze these costs and advocate for evaluating any scheme for drug regulatory tests in terms of concrete empirical benchmarks, like the error rates of regulatory decisions. (shrink)

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and leave (...) unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases. (shrink)

The importance of drug‐metabolizing enzymes in developing mammals has been recently reevaluated in view of the activities and potential inducibilities of these enzymes. The role of endogenous factors raises the question of whether there is a positive regulation of the expression of drug‐metabolizing enzymes by hormones. In humans, among the different isoenzymes of cytochrome P‐450 described in adult liver, only one is absent in 20‐week‐old fetuses. Epoxide hydrolase and glutathione S‐transferases are active while UDP‐glucuronidation develops postnatally. The (...) consequence of this asynchronous rise of activities is briefly discussed. (shrink)

(2010). Drug Detailing in Academic Medical Centers: Regulating for the Right Reasons, with the Right Evidence, at the Right Time. The American Journal of Bioethics: Vol. 10, No. 1, pp. 21-23.

The facilitation of tight regulatory frameworks necessary to ensure that new drugs are safe and effective have yet to be effectively applied within the paediatric population. Utilization of unlicensed and off-label drugs in children results in a variety of problems ranging from inefficacy, adverse reactions and in some cases death. This ethically questionable behaviour has led the European government to legally force pharmaceutical companies to propose paediatric applications and carry out clinical studies at early stages of drug development. The (...) new European Paediatric Regulation implemented in 2007 opens a new era of paediatric drug development and will offer the opportunity to vastly improve children's health. However, this brighter outlook for the paediatric community might encourage potentially unethical behaviour in a pharmaceutical industry that finds itself in economically unstable times. The article records the gradual evolution of the US Paediatric Exclusivity Plan and the underlying principle of the newly introduced European Paediatric Regulation. It discusses some of the potential drawbacks and detrimental consequences of implementing the new European regulation, and the prospects of avoiding these by critically evaluating the difficulties experienced by the US. (shrink)

Many studies have shown that marijuana can negatively affect the cognitive development of adolescents. For some individuals, marijuana use may also initiate opioid use, dose escalation, and opioid use disorder. States that legalize marijuana should help adolescents through regulation of advertising and availability of marijuana-infused edibles. Such policies may assist in protecting neurodevelopment of the adolescent and young adult brain. The federal government should also remove its prohibition of marijuana sales and use, leaving their regulation to state law-makers.

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 (...) class='Hi'>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)

This article examines how scientists and regulators distribute the benefit of the doubt about drug safety under conditions of scientific uncertainty. The focus of the empirical research is the regulatory controversy over the hepatorenal toxicity of benoxaprofen in the United Kingdom and the United States. By scrutinizing the technical coherence of the arguments put forward by industrial and government scientists, it is concluded that these scientists are willing to award the commercial interests of the pharmaceutical industry an enormous benefit (...) of the sccentific doubt, which is not consistent with the best interests of patients. Interpretative flexibility, the burden of proof falling on regulators and their trust in, and dependence on, industrial scientists facilitates that distribution of the benefit of the scientific doubt. However, regulatory authorities' need for viability and the rationality common to opposing scientific views suggest that it is possible, in principle, to alter this dominant trend. To achieve adequate patient protection, drug regulation in the United Kingdom and the United States requires extensive reform. Some preliminary policy changes are sketched. (shrink)

Regulatory agencies vary widely in their classification of FMT, with significant impact on patient access. This article conducts a global survey of national regulations and collates existing FMT classification statuses, ultimately suggesting that the human cell and tissue product designation best fits FMT's characteristics and that definitional objectives to that classification may be overcome.

The history of drug/vaccine development has included major advances guided primarily by risk/benefit analyses concerning the innovative agent, not by evidence-based clinical trials (Phase I–IV). Because the approval for new drugs is hindered under the present process, the system requires restructuring. The Phase I/II study period should be more flexible, using the “environment of knowledge” about the new agent, plus risk/benefit assessments. Phase III, as presently constructed, does not add new adverse events data, it provides a narrower profile of (...) drug efficacy than properly done Phase II studies, and placebo-controlled trials continue to raise unresolved ethical and social issues. Phase III studies should be abandoned for most drugs, and substituted with properly powered Phase II doseranging studies plus careful post-marketing surveillance. Phase III should be a penalty for poor drug development, not a regulatory requirement. (shrink)

Pharmacoresistant schizophrenia is a significant impediment to the successful management of the disease. The expression and function of P‐glycoprotein (P‐gp) has recently been implicated in this phenomenon. P‐gp is a multidrug efflux transporter that prevents drug substrates from crossing the blood–brain barrier (BBB). Although the direct interaction between individual antipsychotic agents and P‐gp has been demonstrated, the effect of antipsychotic drug combinations used in disease management on P‐gp transport function remains to be elucidated. This could have important clinical (...) implications in some individuals as dosage adjustments based on plasma drug concentration changes may not always be appropriate if drug–drug interactions and the resulting changes in drug concentration in the brain are not considered. This paper introduces the potential impact that combination antipsychotic therapy may have on P‐gp function at the BBB and discusses the consequences of this in the prevention and circumvention of unfavourable therapeutic response in schizophrenic disorders. BioEssays 30:183–188, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

One explanation for drug bans is that regulators know more than consumers about product quality. But why not just communicate the information in their ban, perhaps via a “would have banned” label?Because product labeling is cheap-talk, any small market failure tempts regulators to lie about quality, inducing consumers who suspect such lies to not believe everything they are told. In fact, when regulators expect market failures to result in under-consumption of a drug, and so would not ban it (...) for informed consumers, regulators ex ante prefer to commit to not banning this drug for uninformed consumers. (shrink)

Some libertarians tend to advocate the wide availability of cognition-enhancing drugs beyond their current prescription-only status. They suggest that certain kinds of drugs can be a component of a prudential conception of the ‘good life’—they enhance our opportunities and preferences; and therefore, if a person freely chooses to use them, then there is no justification for the kind of prejudicial, authoritative restrictions that are currently deployed in public policy. In particular, this libertarian idea signifies that if enhancements are a prudential (...) ‘good’ for the user, then this can also be construed as a moral good for all rational agents. If this argument is successful, there can be no substantial distinction between the categorical benefits of enhancement, and what is labeled as an enhancement technology. In this paper, I argue that the exclusivity of egotistical choice, and an uncritical deployment of enhancement as a prudential good, underplays the role of a social and political community when creating a procedurally just and effective public policy. Principally, the argument is devoid of any ethical system to permit the external—and therefore public–appreciation of the social context of moral decisions. In effect, libertarian arguments of this sort must disregard any ideas of public ethics, because the liberty to use whatever means available to gain a socio-economic advantage actually extinguishes any professed legitimation strategy. Escaping the procedural aspects of public policy, which are considered integral to authoritative coherence, results in the erosion of any moral obligations. Thus, in a libertarian society, disenfranchised individuals—such as those harmed through addiction—are the unlucky or superfluous product of a liberal and ‘progressive’ society. (shrink)

Earp, Lewis, and Hart make a comprehensive and compelling argument for ending the “war on drugs,” highlighting the importance of both ending the criminalization of people who use drugs, and...

This article probes the advisability of regulating U.S. food and drug safety according to the precautionary principle. To do so, a precautionary regulatory regime is formulated on the basis of the beliefs that motivate most proponents of this initiative. That hypothetical regime is critically analyzed on the basis of an actual instantiation of a similarly stylized initiative. It will be argued that the precautionary principle entails regulatory constraints that are apt to violate basis tenets of political legitimacy. The modifications (...) that would change this finding would also change precautionary regulation to the point that it would be indistinguishable from orthodox safety protocols. It is concluded on the basis of its impoverished content that the precautionary principle should not be taken seriously as a formal approach to the regulation of U.S. food and drug safety. (shrink)

Are universities justified in trying to regulate student use of cognitive enhancing drugs? In this article I argue that they can be, but that the most appropriate kind of regulatory intervention is likely to be voluntary in nature. To be precise, I argue that universities could justifiably adopt a commitment contract system of regulation wherein students are encouraged to voluntarily commit to not using cognitive enhancing drugs. If they are found to breach that commitment, they should be penalized by, (...) for example, forfeiting a number of marks on their assessments. To defend this model of regulation, I adopt a recently-proposed evaluative framework for determining the appropriateness of enhancement in specific domains of activity, and I focus on particular existing types of cognitive enhancement drugs, not hypothetical or potential forms. In this way, my argument is tailored to the specific features of university education, and common patterns of usage among students. It is not concerned with the general ethical propriety of using cognitive enhancing drugs. (shrink)

The US Food and Drug Administration (FDA) is fraught with controversies over the role of values and politics in regulatory science, especially with drugs in the realm of reproductive health. Philosophers and science studies scholars have investigated the ways in which social context shapes medical knowledge through value judgments, and feminist scholars and activists have criticized sexism and injustice in reproductive medicine. Nonetheless, there has been no systematic study of values and gender norms in FDA drug regulation. (...) I focus on three questions about values in regulatory science. First, how have societal values and gender norms shaped the way that the FDA regulates drugs in the realm of reproductive health, specifically with drug labels? Second, what are the ethical, epistemic, and social consequences of these influences on regulation for women and other marginalized groups? Third, which societal values and gender norms ought to influence drug regulation about reproductive health, and how ought this happen? Integrating philosophical analysis with historical archival research and in-depth interviews, I conduct three case studies of drug labeling about reproductive health: (1) the “drug fact” about the mechanism of the morning-after pill; (2) the package inserts for patients about the health risks of oral contraceptives; and (3) the special physician labels made for prescribing drugs to pregnant women. I identify three challenges for the FDA and suggest ways to reduce the influence of sexist values and facilitate feminist alternatives. First, across these cases, I have found that there are many ways in which other concerns in reproductive medicine (such as zygotic life, fetal health, and population control) have devalued women’s health. Second, both knowledge and ignorance xvi about their reproductive health have contributed to women’s oppression, especially poor women and women of color. Finally, by avoiding the epistemic dimensions of ethics, powerful, mostly male parties in medicine (such as doctors, pharmaceutical companies, and religious institutions) have misused “informed consent,” “religious freedom,” and “paternalism” for unethical purposes. For improvement, I suggest extracting sexist values and gender norms from regulatory science that cause epistemic injustices, and I point to success stories for reforming sexism with feminism at the FDA. (shrink)

Drugs addressing unmet medical needs can change the lives of millions. Developing and validating new drugs can, however, take many years. To streamline the assessment of new drugs, regulatory agencies have long established shortened review pathways. Among these programs, Accelerated Approval (AA) has recently come under scrutiny due to the U.S. Food and Drug Administration's decision to authorize Aducanumab, the first Alzheimer's disease drug. This decision attracted fierce criticism due to the allegedly insufficient evidence about the safety and (...) efficacy of the drug. While considerable scholarly attention has been devoted to this case, the ethical aspects of the AA regulatory pathway have so far remained relatively unexplored. In this paper, we set out to fill this gap. We illustrate six conditions that should be met for AA to be ethically acceptable: moral solicitude, evidence, risk mitigation, impartiality, sustainability, and transparency. We discuss such conditions and suggest practical steps to implement them in regulatory and oversight processes. Taken together, our six conditions represent a benchmark for assessing the ethical validity of AA processes and decisions. (shrink)

“Female sexual dysfunction” is the type of contested disease that has sparked concern about the role of the pharmaceutical industry in medical science. Many policies have been proposed to manage industry influence without carefully evaluating whether the proposed policies would be successful. We consider a proposal for incorporating citizen stakeholders into scientific research and show, via a detailed case study of the pharmaceutical regulation of flibanserin, that such programs can be co-opted. In closing, we use Holman’s asymmetric arms race (...) framework as a tool for evaluating policies in industry-funded science. (shrink)

Promotion of prescription drugs may appear to be severely limited in some jurisdictions due to restrictions on direct-to-consumer advertising. However, in most jurisdictions, strategies exist to raise consumer awareness about prescription drugs, notably through the deployment of direct-to-consumer information campaigns that encourage patients to seek help for particular medical conditions. In Canada, DTCI is presented by industry and regulated by Health Canada as being purely informational activities, but their design and integration in broader promotional campaigns raise very similar ethical concerns (...) as those associated with DTCA. Specifically, DTCI can be an effective means of familiarizing the public with the scope and benefits of a particular prescription drug and so, like DTCA, can promote increased patient-consumer demand and thus a problematic rise in the prescribing and use of medications that may be neither the most appropriate nor the most cost-effective. Yet, with DTCI the industry is playing within the existing rules and regulations set by health regulators. To respond appropriately to this regulatory incoherence, we argue that DTCI should be regulated as a type of direct-to-consumer indirect advertising. Even if the case and specific regulations presented here are Canadian, the implications extend to every country that has a partial or total prohibition on DTCA. (shrink)

Drug promotion should be evaluated according to its impact on health, access to information, informed consent, and wealth. Drug promotion currently does more harm than good to each of these objectives because it is usually misleading. This is a systemic problem. Whilst improved regulation and education will address it to some degree, major reforms to payment systems for drug companies and doctors are also required. Until all these systemic reforms can be put in place, the best (...) policy option is to ban the promotion of drugs to doctors and the public. Consequently, pending major reforms, it is appropriate for governments to restrict drug promotion as much as is politically achievable. (shrink)

In this article I attempt to examine the justification for the mandatory drug testing of employees. The justification commonly assumes the form of the productivity argument which states that an employer has a proprietary right to regulate the purchased time of the employee. Since the employer may be rightfully concerned with the employee''s productive output, so this argument goes, the employer retains the right to motivate production. By extension, the employee''s behavior outside of the workplace which affects his or (...) her productive capacity may also be regulated, including drug use which may affect this capacity. Thus it is claimed that the employer has the right to test employees for drug use and to impose sanctions when it is discovered.I argue that the implications of the productivity argument lead to unacceptable consequences and thus must be rejected. The productivity argument can be examined in light of a thought-experiment in which the reader is asked to imagine the discovery of two drugs, both of which enhance employee productivity. Calling these drugs hedonine and pononine, I imagine the first to be pleasurable to the employee while the second is accompanied by a degree of pain and discomfort. Since the mandated use of both of these imagined drugs would be consistent with the productivity argument, I maintain that the productivity argument thereby fails and so must be rejected. As employee drug testing is justified by this argument, it must also be rejected. (shrink)

For the purposes of conservation or suppression of species, gene drive technology has significant potential. Theoretically speaking, with the release of even relatively few animals with gene drive systems in an ecosystem, beneficial or harmful genes could be introduced into the entire wild-type population of that species. Given the profound impact that gene drives could have on species and ecosystems, their use is a highly contentious issue. Communities and groups have differing beliefs about nature and its conservation or preservation, as (...) well as concerns about the ecological safety of the eradication, replacement or enhancement of particular species of animals by means of genetic engineering. For all those reasons, the rigorous regulation of insects and other animals with gene drive systems is crucial. In this paper, we consider the question of whether the United States Food and Drug Administration is prepared to effectively regulate insects and other animals with gene drives. (shrink)

Gerald Dworkin provides an insightful starting point for determining acceptable paternalism through his commitment to protecting our future autonomy and health from lasting damage. Dworkin grounds his argument in an appeal to inherent goods, which this paper argues is best considered as a commitment to human flourishing. However, socialconnectedness is also fundamental to human flourishing and an important consideration when determining the just limits of paternalistic drug controls, a point missing from Dworkin’ essay. For British philosopher Thomas Hill Green, (...) regulation of alcohol sales emerged from the social ideal. Green argued that policy interventions, including restricted opening hours and locations, improved the conditions for humans to flourish. Green offers a compelling political vision but fails to account for the fact pleasure is also an inherent good. He focused excessively on our social nature, excluding our more pleasure-seeking and egoistic characteristics. In contrast, a more realistic and complete vision of human flourishing can be found in an amended version of Gerald’s Dworkin’s arguments. In conclusion, this paper argues drug policy makers should remain committed to the harm principle as applied to criminal law whereby a person should never be criminalized for self-harm. Such a limit on paternalistic interventions is deemed necessary when eudaimonia is the end of government action. In practical terms, this means that the criminalization of drug use, as opposed to drug production, is always unjust. (shrink)

The authors examine the nursing practice of disposing unaltered controlled substances into public water systems as an issue for nurses concerned with the environmental harm it can cause. A summary of the history of controlled substance management reveals inconsistencies in the interpretation of current regulations that have led to disposal policies that vary by institution, according to a benchmarking survey of regional hospitals. Much attention has been given to the phenomenon of conscientious objection in the context of patient care that (...) conflicts with a nurse’s moral integrity. Nurses who are compelled to dispose narcotics down drains may also face this struggle. The authors submit that this disposal method is based on a type of double effect logic where preventing diversion is viewed as a good effect of flushing unused controlled substances that outweighs any harm it may cause, though there is little evidence to support this conclusion. Consequently, the topic deserves further study so that nurse managers and administrators can support and offer alternatives to nurses who object to flushing drugs down the drain. (shrink)

I first became aware of bioethics in the spring of 1980. I had spent a thirty‐six‐hour shift shadowing a medical resident, and I was struck that many of the resident's decisions had ethical dimensions. The next day, I came across the Hastings Center Report, and I realized I wanted to explore ethical issues I found implicit in clinical care, even though I still wanted to become a pediatrician. In September 2019, when I attended my first meeting of the U.S. Food (...) and Drug Administration's Pediatric Advisory Committee, as a pediatric pulmonologist, I had the same sense of awe and curiosity that I had forty years ago. What had appeared initially as somewhat technical decisions about the regulation of drug labeling was suffused with ethical questions. The committee was asked to discuss possible changes to the labeling of two previously approved drugs. (shrink)

This article describes the shortage of generic injectable medications in Canada that affected hospitals in 2012. It traces the events leading up to the drug shortage, the causes of the shortage, and the responses by health administrators, pharmacists, and ethicists. The article argues that generic drug shortages are an ethical problem because health care organizations and governments have an obligation to avoid exposing patients to resource scarcity. The article also discusses some options governments could pursue in order to (...) secure the drug supply and thereby fulfill their ethical obligations. (shrink)

The pharmaceutical industry has in recent years come under attack from an ethical point of view concerning its patents and thenon-accessibility of life-saving drugs for many of the poor both in less developed countries and in the United States. The industry has replied with economic and legal justifications for its actions. The result has been a communication gap between the industry on the one hand and poor nations and American critics on the other. This paper attempts to present and evaluate (...) the arguments on all sides and suggests a possible way out of the current impasse. It attempts to determine the ethical responsibility of the drug industry in making drugs available to the needy, while at the same time developing the parallel responsibilities of individuals, governments, and NGOs. It concludes with the suggestion that the industry develop an international code for its self-regulation. (shrink)

The pharmaceutical industry has in recent years come under attack from an ethical point of view concerning its patents and thenon-accessibility of life-saving drugs for many of the poor both in less developed countries and in the United States. The industry has replied with economic and legal justifications for its actions. The result has been a communication gap between the industry on the one hand and poor nations and American critics on the other. This paper attempts to present and evaluate (...) the arguments on all sides and suggests a possible way out of the current impasse. It attempts to determine the ethical responsibility of the drug industry in making drugs available to the needy, while at the same time developing the parallel responsibilities of individuals, governments, and NGOs. It concludes with the suggestion that the industry develop an international code for its self-regulation. (shrink)

Recent developments in neuroscience have enabled technological advances to modulate cognitive functions of the brain. Despite ethical concerns about cognitive enhancement, both individuals and society as a whole can benefit greatly from these technologies, depending on how we regulate their use. To date, regulatory analyses of neuromodulation technologies have focused on a technology itself – for instance, the U.S. Food and Drug Administration regulation of a brain stimulation device – rather than the use of a technology, such as (...) the use of a brain stimulation device at work or school. Given that some forms of cognitive enhancement have already started to penetrate the general public’s everyday life, we should begin our discussion on potential regulatory issues regarding their use in various real-world situations. The goal of the article is to fill the gap by providing an analytic framework to examine these regulatory issues. More specifically, it aims to illustrate the issues around respecting autonomy and preventing coercive use of cognitive enhancement. The proposed framework categories the real-world settings where a neuromodulation technology can be used for cognitive enhancement based on two criteria – who is subjected to cognitive enhancement and who imposes cognitive enhancement. Based on this framework, the article analyzes regulatory issues arising out of every combination of subject/imposing party by taking one example case. Focusing on the regulations in the U.S., this analysis shows the current lack of adequate safeguards against the coercive use and calls for more attention from government agencies and researchers to develop sound policies regarding current and potentially more widespread use of cognitive enhancement. (shrink)

Medicine regulation demands the application of sound medical, scientific, and technical knowledge and skills, and operates within a legal framework. Regulatory functions involve interactions with various stakeholders (e.g., manufacturers, traders, consumers, health professionals, researchers, and governments) whose economic, social, and political motives may differ, making implementation of regulation both politically and technically challenging. This book discusses regulatory landscape globally and the current global regulatory scenario of medicinal products and food products comprehensively.

Hypocretin regulates brain reward function and cocaine consumption in rats. The hypocretinergic (Hcrt) system is implicated in energy homeostasis, feeding and sleep regulation. Hypocretinergic cell bodies are located in the lateral hypothalamus (LH) and project throughout the brain. The aim of the present studies was to investigate the role of the Hcrt system in regulating brain reward function and the reinforcing properties of cocaine in rats. Intracranial self-stimulation (ICSS) thresholds provide an accurate measure of brain reward function in rats. (...) Here we show that a single injection of Hcrt-1 (5 µg icv) induced persistent, long-lasting elevations in ICSS thresholds in drug-naïve rats. Indeed, Hrct-1 elevated ICSS thresholds for 36 h, with peak elevations between 6 and 12 hours after injection. Hrct-1-induced threshold elevations were attenuated by an antibody known to neutralize the binding of hcrt-1 to its receptors. Taken together, these observations suggest that Hrct-1 negatively regulates brain reward function in rats. Because Hrct-1 negatively regulates brain reward function, we hypothesized that it may attenuate the increased brain reward function usually observed after cocaine consumption, and thereby alter cocaine self-administration behavior. A daily injection of Hrct-1 (1 µg icv), for 4 consecutive days, slightly increased cocaine self-administration (0.25 mg/infusion) in rats. Overall, these data demonstrate that Hrct-1 negatively regulates brain reward function, and as such may indirectly alter cocaine self-administration. Given the well-established role of hypocretin neurons in regulating feeding behavior and sleep, we hypothesize that hypocretinergic regulation of brain reward function may provide a mechanism by which appropriate and competing behaviors (e.g. sleep or feeding) may be engaged to maintain energy homeostasis. (shrink)

Regulating clinical trials for testing new drugs is fraught with risk. Misregulation can slow development of innovative and useful new drugs, but in other ways misregulation can foster trials that are inefficient and unethical, driven by commercial rather than scientific ends, and that can harm patients. In this paper, we argue not for more but for better regulation, based on the goal of rapidly producing innovative and safe products that represent significant advances in medical care. Data on industry-funded, late-stage (...) clinical trials demonstrate an urgent need for dramatic changes in how these trials are designed, conducted, and analyzed. On the one hand, current patent rules can dissuade development of innovative new products with smaller markets and press trial designers to create positive results too rapidly. But at the same time, numerous studies show that when the pharmaceutical industry sponsors clinical trials, the results are systematically biased in favor of the sponsor's product, often to the detriment of patients and the public. The reasons for this bias are both complex and unavoidable, and the ways in which clinical trial design, conduct, and reporting can be inappropriately influenced are so varied and nuanced, that efforts to manage this conflict of interest and prevent harms are inevitably unsuccessful. Instead, we conclude such conflict should be avoided and a strong firewall should exist between drug developers and the final stages of clinical testing in humans. All financial support for phase III clinical trials should pass through a public-private partnership organization — perhaps tied to a broader clinical effectiveness research enterprise — which would be charged with designing, funding, and monitoring late-stage human clinical trials of new pharmaceutical products. (shrink)