This book examines how regulatory and liability mechanisms have impacted upon product safety decisions in the pharmaceutical and medical devices sectors in Europe, the USA and beyond since the 1950s. Thirty-five case studies illustrate the interplay between the regulatory regimes and litigation. Observations from medical practice have been the overwhelming means of identifying post-marketing safety issues. Drug and device safety decisions have increasingly been taken by public regulators and companies within the framework of the comprehensive regulatory (...) structure that has developed since the 1960s. In general product liability cases have not identified or defined safety issues, and function merely as compensation mechanisms. This is unsurprising as the thresholds for these two systems differ considerably; regulatory action can be triggered by the possibility a product is harmful, whereas establishing liability in litigation requires proving that the product was actually harmful.As litigation normally post-dates regulatory implementation, the 'private enforcement' of public law has generally not occurred in these sectors. This has profound implications for the design of sectoral regulatory and liability regimes, including associated features such as extended liability law, class actions and contingency fees. This book forms a major contribution to the academic debate on the comparative utility of regulatory and liability systems, on public versus private enforcement, and on mechanisms of behaviour control. (shrink)

Industry control over the production and distribution of pharmaceutical safety and efficacy data has become a serious public health and health care funding concern. Various recent scandals, several involving the use of flawed representations of scientific data in the most influential medical journals, highlight the urgency of enhancing pharmaceutical knowledge governance. This paper analyzes why this is a human rights concern and what difference a human rights analysis can make. The paper first identifies the challenges associated with (...) the current knowledge deficit. It then discusses, based on an analysis of case law, how various human rights associated interests can be invoked to support the claim that states have an obligation to actively contribute to independent knowledge governance, for example through ensuring clinical trials transparency. The paper further discusses a conceptual use of human rights, as a methodology which requires a comprehensive analysis of the different interwoven historical, economic, cultural, and social factors that contribute to the problem. Such an analysis reveals that historically grown drug regulations have, in fact, contributed directly to industry control over pharmaceutical knowledge production. This type of finding should inform needed reforms of drug regulation. The paper ends with a recommendation for a comprehensive global response to the problem of pharmaceutical knowledge governance. (shrink)

The rapid increase of industry-sponsored clinical research towards developing countries has led to potentially complex ethical issues to assess. There is scarce evidence about the perception of these participants about the ethical compliance, security, and protection. We sought to evaluate and contrast the awareness and perception of participants and non-participants of industry-sponsored research trials on ethical, safety, and protection topics. A Cases-control survey conducted at twelve research sites in México. Previous and current participants of ISRT as well as non-participants (...) with one of four chronic diseases, were asked to complete the survey which focused on ethical compliance and protection issues of ISRT, and the perception of participating in a trial. A total of 604 cases and 604 controls were surveyed. Cases significantly answered that ethics committees are aware of what is happening in studies, and that medical care of industry-sponsored research trials is better than their usual medical care. The same proportion of cases and controls thought patients must receive economical reimbursement for participating in a research study. The informed consent of the pharmaceutical clinical trial was fully read by 90.4% of the cases. Most cases were satisfied or very satisfied with their overall study participation. Previous and current participants of industry-sponsored research trials have a more positive attitude towards ethics committees, the quality of medical care of the research trials, and the main purpose of economical reimbursements, when compared to non-participants. (shrink)

Risk communication has been generally categorized as a warning act, which is performed in order to prevent or minimize risk. On the other side, risk analysis has also underscored the role played by information in reducing uncertainty about risk. In both approaches the safety aspects related to the protection of the right to health are on focus. However, it seems that there are cases where a risk cannot possibly be avoided or uncertainty reduced, this is for instance valid for (...) the declaration of side effects associated with pharmaceutical products or when a decision about drug approval or retirement must be delivered on the available evidence. In these cases, risk communication seems to accomplish other tasks than preventing risk or reducing uncertainty. The present paper analyzes the legal instruments which have been developed in order to control and manage the risks related to drugs – such as the notion of “development risk” or “residual risk” – and relates them to different kinds of uncertainty. These are conceptualized as epistemic, ecological, metric, ethical, and stochastic, depending on their nature. By referring to this taxonomy, different functions of pharmaceutical risk communication are identified and connected with the legal tools of uncertainty management. The purpose is to distinguish the different functions of risk communication and make explicit their different legal nature and implications. (shrink)

Women’s health activists laid the groundwork for passage of the law that created the U.S. Food and Drug Administration in 1906. The pharmaceutical and food industries fought regulatory reforms then and continue to do so now. We examine public health activism in the Progressive Era, the postwar era and the present day. The women’s health movement began in the 1960s, and criticized both the pharmaceutical industry and the medical establishment. In the 1990s, patient advocacy groups began accepting industry (...) funds; thousands of commercially-funded groups now dominate the advocacy landscape. As pharma funding became normalized, concerns arose regarding a) the lack of transparency and public accountability regarding funding, b) the distortion of groups’ agendas, and c) the ability of pharma-funded groups to dominate the discourse and override less well-resourced patient and health advocacy groups. Although industry-funded groups argue that funding allows them to provide useful services, the trade-off in health risks, exorbitant prices and distorted information is far too high. Sincerity is beside the point; patients and the industry have differing interests when it comes to drug safety and efficacy, drug information and drug prices. A growing resistance movement is asserting the values of its activist predecessors and opposing the prevailing culture of pharma-funded advocacy. (shrink)

Good decision-making requires reliable information. In medicine, relevant information comes from clinical trials and other forms of scientific research. In business, one source is in corporate annual financial statements. As for-profit, publicly traded companies whose business is discovering, manufacturing, and marketing drugs, pharmaceutical companies sit at the nexus of these two fields. Determining the safety and efficacy of a pharmaceutical product and determining the profitability of a complex enterprise are similarly difficult tasks: each is fraught with deeply (...) ambiguous information that requires sophisticated judgment to interpret reasonably. (shrink)

The point, for the 946,326th time is that people get elected to office by currying the favor of powerful interest groups. They don’t get elected for their excellence as political philosophers.Congress has consistently failed to solve some serious problems with the cost, effectiveness, and safety of pharmaceuticals. In part, this failure results from the pharmaceutical industry convincing legislators to define policy problems in ways that protect industry profits. By targeting campaign contributions to influential legislators and by providing them (...) with selective information, the industry manages to displace the public’s voice in developing pharmaceutical policy. (shrink)

In recent years, the development process of pharmaceuticals, medical devices, and related products and the overall market of these products have become increasingly global. This paper discusses the need for better governance of one aspect of this market: the production, distribution, and use of pharmaceutical knowledge. Various controversies, some of which will be described in this paper, highlight how industry control over pharmaceutical data production has resulted in very serious threats to public health. Different practices and regulatory fields (...) that affect what I will refer to in this paper as “pharmaceutical knowledge production” are all too often artificially separated and dealt with in isolation, which seriously affects the quality of the available information on the safety and effectiveness of products. I will examine here how a human rights-based approach should inspire us to look more carefully not only at the significant human rights-related interests that are at stake, but also at the relations between the different interwoven regulatory, cultural, and social factors and how these play out at the various stages of knowledge production. (shrink)

Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the (...) FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board. (shrink)

Advertisements for pharmaceuticals may promote placebo responses by generating an expectation of therapeutic success. Some cite this as reason to favour Direct to Consumer Advertising of Prescription Pharmaceuticals (DTCA). Against this, I show placebo responses to emanate from beliefs rendered unjustified by the influence of a conditioning process. I argue that drug safety and efficacy are material properties and that unjustified beliefs in these domains entail costs to autonomy that outweigh any prudential gains attending a placebo response. I conclude (...) that its placebogenic potential ought not to count as reason to favour DTCA. (shrink)

Today, the goals of pharmaceutical policy and medical practice are often undermined due to institutional corruption — that is, widespread or systemic practices, usually legal, that undermine an institution's objectives or integrity. In this symposium, 16 articles investigate the corruption of pharmaceutical policy, each taking a different look at the sources of corruption, how it occurs, and what is corrupted. We will see that the pharmaceutical industry's own purposes are often undermined. Furthermore, pharmaceutical industry funding of (...) election campaigns and lobbying skews the legislative process that sets pharmaceutical policy. Moreover, certain practices have corrupted medical research, the production of medical knowledge, the practice of medicine, drug safety, the Food and Drug Administration's oversight of the pharmaceutical market, and the trustworthiness of patient advocacy organizations. (shrink)

To sell a new drug, pharmaceutical companies must discover a compound, run clinical trials to test its efficacy and safety, get it approved by regulatory bodies, produce the drug, and market it. As this process brings the drug through so many hands, there are risks of many kinds of corruption. The pharmaceutical industry has recently gone from being one of the most admired industries to being described by the majority of Americans as “dishonest, unethical, and more concerned (...) with profits than with individual and public health.” Legal scholar Marc Rodwin suggested that the pharmaceutical industry can be viewed through the lens of institutional corruption as defined by legal scholar Lawrence Lessig, whereby widespread or systemic practices undermine the main purposes of drug therapy — healing illness, preventing medical problems, and alleviating suffering. Many drugs do serve these goals, yet a significant number of drugs churned out by pharmaceutical companies are ineffective or have dangerous side effects that could have been predicted had the companies conducted the appropriate research. (shrink)

Direct-to-consumer advertising (DTCA) of prescription drugs has been a heavily contested issue over the past decade, touching on several issues of responsibility facing the pharmaceutical industry. Much research has been conducted on DTCA, but hardly any studies have discussed this topic from a corporate social responsibility (CSR) perspective. In this article, we use several elements of CSR, emphasising consumer autonomy and safety, to analyse differences in DTCA practices within two different policy contexts, the United States of America and (...) the European Union (EU). Doing so results in an alternative analysis of the struggle between proponents and opponents of DTCA from a CSR perspective, adding an alternative view on this debate. (shrink)

There is growing interest among pharmaceutical policymakers in how to “disinvest” from subsidized medicines. This is due to both the rapidly rising costs of healthcare and the increasing use of accelerated and conditional reimbursement pathways which mean that medicines are being subsidized on the basis of less robust evidence of safety and efficacy. It is crucial that disinvestment decisions are morally sound and socially legitimate, but there is currently no framework to facilitate this. We therefore reviewed the bioethics (...) literature in order to identify ethical principles and concepts that might be relevant to pharmaceutical disinvestment decisions. This revealed a number of key ethical considerations—both procedural and substantive—that need to be considered when making pharmaceutical disinvestment decisions. These principles do not, however, provide practical guidance so we present a framework outlining how they might be applied to different types of disinvestment decisions. We also argue that, in this context, even the most rigorous ethical reasoning is likely to be overridden by moral intuitions and psychological biases and that disinvestment decisions will need to strike the right balance between respecting justifiable moral intuitions and overriding unjustifiable psychological impulses. (shrink)

The risk that direct-to-consumer advertising of prescription pharmaceuticals (DTCA) may increase inappropriate medicine use is well recognized. The U.S. Food and Drug Administration addresses this concern by subjecting DTCA content to strict scrutiny. Its strictures are, however, heavily focused on the explicit claims made in commercials, what we term their “propositional content.” Yet research in social psychology suggests advertising employs techniques to influence viewers via nonpropositional content, for example, images and music. We argue that one such technique, evaluative conditioning, is (...) operative in DTCA. We further argue that evaluative conditioning fosters unjustified beliefs about drug safety and efficacy, antagonising the autonomy of viewers’ choices about advertised medicines. We conclude that current guidelines are deficient in failing to account for evaluative conditioning, and that more research and debate are needed to determine the permissibility of this and other forms of nonpropositional persuasion. (shrink)

As one of the most massive and successful business sectors, the pharmaceutical industry is a potent force for good in the community, yet its behaviour is frequently questioned: could it serve society at large better than it has done in the recent past? Its own internal ethics, both in business and science, may need a careful reappraisal, as may the extent to which the law - administrative, civil and criminal - succeeds in guiding (and where neccessary contraining) it. The (...) rules of behavior that may be considered to apply to today's pharmaceutical industry have emerged over a very long period and the process goes on. Even the immensely detailed standards for quality, safety and efficacy laid down in drug law and regulation during the second half of the twentieth century have their limitations as tools for ensuring that the public interest is well served. In particular, national and regional regulatory agencies are heavily dependent on industrial data for their decision-making, their standards and competence vary, and even the existing network of agencies does not cover the entire world. What is more there are many areas of law and regulation affecting the industry, concerning for example the pricing of medicines, the conduct of clinical studies, the health protection of workers and concern for the environment. In some fields it is indeed hardly possible to maintain standards through regulation. Professor N.M. Graham Dukes, a physician and lawyer with long term experience in industrial research management, academic study and international drug policy, provides here a powerfully documented analysis into the way this industry thinks, acts, and is viewed, and examines the current trends pointing to change. *Provides a balanced picture of the current role of the pharmaceutical industry in society *Includes indices of conventions, laws, and regulations; as well as judicial and disciplinary cases *This is the only book addressing the legal implications of big pharma activities and ethical standards. (shrink)

Improper dependencies slant policy over a drug's life span, biasing the development of new drugs, the testing and marketing approval for new drugs, and the monitoring of patient safety after drugs are marketed. This article examines five ways in which the public improperly depends on pharmaceutical firms that compromise the integrity of pharmaceutical policy. Today the public relies on pharmaceutical firms: (1) to set priorities on drug research and development; (2) to conduct clinical trials to test (...) whether drugs are safe and effective; (3) to decide what clinical trial data to disclose to the public; (4) to monitor post marketing drug safety; (5) to supply product information to physicians and to finance continuing medical education and other professional activities. The article suggests options to overcome each of these dependencies. (shrink)

Transgenic plants are now being used to develop pharmaceutical and industrial products in addition to their use in crop improvement. Using confinement requirements, these transgenic plants are grown and processed under conditions that prevent intermixing with commodity crops. Regulatory agencies in the United States have provided guidance of zero tolerance of these new industrial crops with commodity crops. While this is a worthy goal, it is theoretically unattainable. In spite of the best containment practices, there is a potential risk (...) using any system of production due to unforeseen incidences including natural disasters or exposure to workers. The precautionary principle has been used for numerous regulated articles in addressing the potential risks of new products and technology based on a risk assessment in similar situations. We present here a risk assessment model that could be used as a start to develop an accepted model for the industry. The model is based on current risk models used for other regulated articles, but adapted for these types of products. This could be used to determine action levels in the event of an unintended exposure or to ensure that detection or confinement methods are adequate to avoid risks. As an example, aprotinin, a therapeutic protein now being produced in maize, was evaluated for potential risk to humans using this model. (shrink)

The paper considers the legal tools that have been developed in German pharmaceutical regulation as a result of the precautionary attitude inaugurated by the Contergan decision. These tools are the notion of “well-founded suspicion”, which attenuates the requirements for safety intervention by relaxing the requirement of a proved causal connection between danger and source, and the introduction of the reversal of proof burden in liability norms. The paper focuses on the first and proposes seeing the precautionary principle as (...) an instance of the requirement that one should maximise expected utility. In order to maximise expected utility certain probabilities are required and it is argued that objective Bayesianism offers the most plausible means to determine the optimal decision in cases where evidence supports diverging choices. (shrink)

A prime is a cue that makes associated concepts, behaviors, and goals more psychologically accessible to people, influencing their responses in subsequent related environments. I build a case that Direct to Consumer Advertising of Prescription Pharmaceuticals (DTCA) operates as a prime that causes some viewers to prefer and pursue the advertised drug. Drawing on literature from social psychology I show that people subject to priming are mostly unaware of its influence and liable to misattribute the reasons for their primed actions. (...) Misattribution typically includes heightened appraisals of the value of a primed goal. Consistent with this account, I argue that viewers primed by DTCA hold favorable, yet false beliefs about the safety and efficacy of the advertised drug. I further argue that, because those drug properties are material to viewers with the relevant illness, priming in DTCA can undermine the autonomy of their medicine choices. The threat to autonomy posed by priming in DTCA suggests it warrants attention from both regulators and the wider research community. It also adds further reason to be sceptical about the permissibility of this form of advertising. (shrink)

Direct-to-consumer advertising (DTCA) of prescription drugs has been a heavily contested issue over the past decade, touching on several issues of responsibility facing the pharmaceutical industry. Much research has been conducted on DTCA, but hardly any studies have discussed this topic from a corporate social responsibility (CSR) perspective. In this article, we use several elements of CSR, emphasising consumer autonomy and safety, to analyse differences in DTCA practices within two different policy contexts, the United States of America and (...) the European Union (EU). Doing so results in an alternative analysis of the struggle between proponents and opponents of DTCA from a CSR perspective, adding an alternative view on this debate. (shrink)

Children deserve optimal medical care. Although prescription drugs play a prominent and essential role in pediatric health care delivery, health care providers often must make prescribing decisions for their young patients based on imperfect or absent safety and efficacy data for pediatric populations. Until relatively recently, the Food and Drug Administration made surprisingly little effort to improve the quality or quantity of clinical research data for this patient group. Despite recent agency efforts to improve the situation, only one-third of (...) drugs prescribed to children currently have been studied for safety and efficacy in pediatric populations. Moreover, recent agency initiatives to encourage pediatric drug research have generated mixed results and unintended consequences. The complex of issues surrounding the testing and prescribing of prescription drugs used for children will require that pharmaceutical companies, the FDA, and health care providers examine current practices, acknowledge their shortcomings, and consider cooperative, creative solutions. (shrink)

ABSTRACTIn April of 2000, Diana Levine went to a clinic in Vermont suffering from a migraine headache. She was given the drug Demerol for the migraine symptoms and Phenergan for nausea. Complications with the administration of Phenergan ultimately resulted in Ms. Levine contracting gangrene, necessitating the amputation of her right arm. Ms. Levine sued the drug maker, Wyeth Pharmaceutical, in state court and prevailed. The lower court's decision was appealed by Wyeth to the state supreme court where the ruling (...) was confirmed. Wyeth next appealed to the U.S. Supreme Court which, to the surprise of many observers, affirmed the judgment of the state supreme court. At issue was the fundamental question of the ability of consumers to obtain redress against negligent manufacturers in state courts. Wyeth's arguments to the Court were based upon preemption: Foodand Drug Administration approval of a drug preempts the ability of injured consumers like Ms. Levine to recover in state courts despite years of precedent to the contrary. Ability to recover damages in state courts represents, perhaps, the most important safety net available to consumers injured by defective products. A ruling by the Supreme Court that FDA‐approved labeling of pharmaceuticals preempts the reach of the state courts would have severely compromised the balance of power between consumers and producers. (shrink)

In the wake of several highly publicized lawsuits over drugs recalled for safety – most notably, Vioxx and Paxil – the Food and Drug Administration and the pharmaceutical industry have faced increasingly intense public scrutiny over the drug testing and approval process. Critics blame the FDA's shorter pre-market approval process that has resulted from the enactment of the Prescription Drug User Fee Act, which effected, among other changes, an increased number of reviewers, a higher review load for each (...) reviewer, and the implementation of “user fees” from companies submitting drugs for review. While many have posited that the lack of safety in some FDA-approved drugs was caused by the enactment of PDUFA, the results of a recent study from the Tufts Center for the Study of Drug Development have indicated that there is no statistically significant correlation between the number of drugs recalled for safety and the enactment of PDUFA. (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)

Drawing on case studies from the modern era of pharmaceutical regulation in the UK, US and Europe, I examine how the extent and distribution of trust between regulators, the pharmaceutical industry, and the medical profession about drug testing and monitoring influences knowledge and regulatory judgements about the efficacy and safety of prescription drugs. Introducing the concepts of ‘acquiescent’ and ‘investigative’ norms of regulatory trust, I demonstrate how investigative norms of regulatory trust—which deter pharmaceutical companies from assuming (...) that their data analyses will be accepted without independent de-construction—drive up bioethical and regulatory standards of drug assessment in the interests of health. By contrast, acquiescent norms of regulatory trust, which are associated with industrial capture and professional closure of interests, promote permissive standards allowing patients to take pharmaceuticals with greater risks to health and less evidence of therapeutic efficacy. (shrink)

The introduction of automated vehicles promises an increase in traffic safety. Prior to its launch proof of the anticipated reduction in the sense of a positive risk balance compared with human driving performance is required from various stakeholders such as the European Union Commission, the German Ethic Commission, and the ISO TR 4804. To meet this requirement and to generate acceptance by the public and the regulatory authorities, a qualitative Risk- Benefit framework has been defined. This framework is based (...) on literature research on approaches applied in other disciplines. This report depicts the framework, adapted from the pharmaceutical sector called PROACT-URL which serves as a structured procedure to demonstrate a positive risk balance in an understandable and transparent manner. The qualitative framework needs to be turned in quantitative methods once it should be applied. Therefore, two steps of the framework are discussed in more detail: First, the definition of adequate development thresholds that are required at an early stage of the development. Second the simulation-based assessment to prove the positive risk balance prior to the market introduction. (shrink)

The need to better balance the promotion of scientific and technological innovation with risk management for consumer protection has inspired several recent reforms attempting to make regulations more flexible and adaptive. The pharmaceutical sector has a long, established regulatory tradition, as well as a long history of controversies around how to balance incentives for needed therapeutic innovations and protecting patient safety. The emergence of disruptive biotechnologies has provided the occasion for regulatory innovation in this sector. This article investigates (...) the regulation of advanced biotherapeutics in the European Union and shows that it presents several defining features of an adaptive regulation regime, notably institutionalized processes of planned adaptation that allow regulators to gather, generate, and mobilize new scientific and risk evidence about innovative products. However, our in-depth case analysis highlights that more attention needs to be paid to the consequences of the introduction of adaptive regulations, especially for critical stakeholders involved in this new regulatory ecosystem, the capacity and resource requirements placed on them to adapt, and the new tradeoffs they face. In addition, our analysis highlights a deficit in how we currently evaluate the performance and public value proposition of adaptive regulations vis-à-vis their stated goals and objectives. (shrink)

This article tracks the transformation of beagle dogs from a common breed in mid-twentieth century American laboratories to the de jure standard in global toxicological research by the turn of the twenty-first. The breed was dispersed widely due to the expanding use of dogs in pharmacology in the 1950s and a worldwide crisis around pharmaceutical safety following the thalidomide scandal of the 1960s. Nevertheless, debates continued for decades over the beagle’s value as a model of carcinogenicity, even as (...) the dogs became legislated stand-ins for human beings in multiple countries. Situating beagles as a biocommodity, the article calls for more sustained attention to the “political economy” of laboratory organism breeding, use, and production. The story of American commercial breeder Marshall Farms offers insight into the role of for-profit companies in contemporary laboratory animal provision, as the article makes a case for the value of a global perspective on transnational corporations as key sites of scientific practice and collaboration. (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)

Safety testing of biological pharmaceuticals is often carried out by contract testing laboratories which perform these tests on behalf of the drug’s developer. These laboratories are confronted with a number of ethical issues related to selling their services, maintaining confidentiality, and the handling of results. This paper outlines these issues, and, by way of illustration, discusses how one such laboratory addresses them.

The Dobbs opinion emphasizes that the state’s interest in the fetus extends to “all stages of development.” This essay briefly explores whether state legislators, agencies, and courts could use the “all stages of development” language to expand reproductive surveillance by using novel developments in consumer health technologies to augment those efforts.

Medical ghostwriting is the practice in which pharmaceutical companies engage an outside writer to draft a manuscript submitted for publication in the names of “honorary authors,” typically academic key opinion leaders. Using newly-posted documents from paroxetine litigation, we show how the use of ghostwriters and key opinion leaders contributed to the publication of a medical journal article containing manipulated outcome data to favor the proprietary medication. The article was ghostwritten and managed by SmithKline Beecham, now GlaxoSmithKline (GSK) and Scientific (...) Therapeutics Information, Inc. without acknowledging their contribution in the published article. The named authors with financial ties to GSK, had little or no direct involvement in the paroxetine 352 bipolar trial results and most had not reviewed any of the manuscript drafts. The manuscript was originally rejected by peer review; however, its ultimate acceptance to the American Journal of Psychiatry was facilitated by the journal editor who also had financial ties to GSK. Thus, GSK was able to take an under-powered and non-informative trial with negative results and present it as a positive marketing vehicle for off-label promotion of paroxetine for bipolar depression. In addition to the commercial spin of paroxetine efficacy, important protocol-designated safety data were unreported that may have shown paroxetine to produce potentially harmful adverse events. (shrink)

The COVID-19 pandemic underscored longstanding fissures in China's business relationships with the West. If the West is going to develop a relationship of mutual trust, and improve business relations with China in the coming decades, it is imperative to understand how to engage with Chinese thinking on ethics in business-this book explains how. Policy-makers, businesspeople and business-ethicists have trouble communicating about issues in ethics, policy and business across the China-West divide. This book shows how to overcome the us-versus-them mindset plaguing (...) China-West relations by presenting to Western audiences an easy-to-understand yet deeply informed primer on core ideas and perspectives in Chinese cultural and philosophical thought. The book considers original texts of Chinese philosophy and religion, and applies principles from those writings to three business ethics topics of enduring interest to business executives, policy makers, and academics, namely, the protection of intellectual property, assurance of product safety and quality in the pharmaceutical supply chain, and human rights. This book is a must-read for those who want to forge constructive relationships with their Chinese counterparts based on mutual trust and understanding. The book is specifically relevant to business executives, but it should also be of interest to policymakers, educators and students who seek to communicate more effectively with their Chinese counterparts, in particular about difficult and contentious business, policy, and ethical issues. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Introduction to the Special Section on Psychedelics Research and TreatmentDominic SistiAgainst a backdrop of post-pandemic malaise, diseases of despair, and a fragmented mental health care system, psychedelics have enjoyed a resurgence of interest as powerful psychotherapeutic agents and as catalysts of personal growth. The true power of these substances—some of which are considered sacramental by Indigenous peoples—has been shrouded for half a century by cultural mythology, political propaganda, and (...) misuse. From about 1940 to 1970, psychedelics including psilocybin and LSD were studied and used by clinicians to treat a range of psychiatric disorders from alcoholism and depression in adults to "autistic schizophrenia" in children.In June 1971, the Nixon administration's racist and illiberal War on Drugs inaugurated what was essentially a total ban on psychedelics. Society was robbed of half a century of scientific progress, and one can only speculate how differently our society might now function, and how many people might have been spared the trauma of mental illness and incarceration. Thankfully, it appears the time has arrived for psychedelic medicines to be decriminalized and included again in the pharmacopeia.In June 2023, a group of psychedelic researchers, therapists, bioethicists, Indigenous scholars, and advocates met at the Banbury Conference Center at Cold Spring Harbor Laboratory. There, this interdisciplinary group discussed several pressing ethical issues in psychedelics research and treatment that continue to [End Page 114] challenge the field. The aim of this meeting was to develop a bioethical framework for the use of psychedelics in mainstream medical settings. That is, how should psychedelics be employed responsibly by everyday clinicians, including psychiatrists, psychologists, social workers, and other behavioral health-care providers? This special section offers a sampling of three topics in psychedelic bioethics raised by the Banbury group, several of whom appear as coauthors.In our first paper, Logan Neitzke-Spruill and colleagues offer an overview of explanatory models describing the therapeutic mechanisms of psychedelic substances and how each of these models generates unique ethical quandaries. Starting from molecular biology and moving to neural circuitry and networks, neurobiological models now propel contemporary scientific research into psychedelics. Knowing how these substances work on a molecular level may offer promising ways forward in the development of new molecules designed to treat serious mental illnesses and other neurologic conditions. Perhaps neuroplastic mechanisms will be harnessed to develop new therapies without necessitating a psychedelic trip—a controversial premise discussed in our third paper, by Katherine Cheung, Brian Earp, and David Yaden.Such "neuroreductionism" risks ignoring the subjective psychological and spiritual experiences of patients that appear to be pivotal in psychedelic-assisted therapy, often described as mystical and utterly transformative. At the psychological level, these substances engender a kind of vulnerability and suggestibility requiring clear ethical standards to ensure patients' psychological and physical safety. And so too, practitioners will need structural and cultural competency to recognize the spiritual or moral values that inspire patient reactions during and after their psychedelic experiences. Ethically informed psychedelic practitioners will have to navigate between disciplinary silos and explanatory models. One practical upshot is the open question of how best to train psychedelic practitioners who hold this broad set of competencies.To that end, well-trained practitioners will need to be able to disclose in some way the transformative properties of psychedelics to prepare patients for their experiences. But how does one describe the ineffable? This raises the question of how or if it is possible for patients to truly consent to the transformative experience elicited by psychedelics, often described as one of the most important experiences of a person's life. The experience might stimulate significant emotional healing, or it might be horrifying. This sounds like a problem uniquely attached to psychedelics: after all, most pharmaceuticals don't trigger changes in one's fundamental moral values, life choices, and commitments, nor are they intended to. Yet, Brent Kious, Andrew Peterson, and Amy McGuire challenge the view that the psychedelic experience is uniquely transformative and impervious to the disclosure requirements of informed consent, a bedrock of bioethics. Ultimately, the writers show how consent is possible even if the experiences are dramatically different from most medical interventions, endorsing a practical view of consent [End... (shrink)

Based on the experiences of two high profile voluntary data collection programs for engineered nanomaterials, this article considers the merit of an international online registry for scientific data on engineered nanomaterials and environmental, health and safety (EHS) data. Drawing on the earlier experiences from the pharmaceutical industry, the article considers whether a registry of nanomaterials at the international level is practical or indeed desirable, and if so, whether such an initiative—based on the current state of play—should be voluntary (...) or mandatory. The article commences with an examination of the success and failures of voluntary reporting schemes in the UK and the US, as well as the International Council of Nanotechnology’s EHS Database and the OECD’s Working Party on Manufactured Nanomaterials. The article then examines the history of clinical trials registries, including the key motivations behind their creation, the role of self-regulation, and the perceived benefits thereof. Key lessons of the rise of clinical trials registration are highlighted, as are crucial considerations that must be addressed by policy makers should a multi-lateral public registry for data on nanoscale materials and EHS research be perceived to be a desirable option. The article concludes by arguing that while the creation of a registry to record information generated on nanomaterials is not straightforward, this reason alone should not deter industry from taking a proactive approach to the dissemination of fundamental data and research findings. (shrink)

Despite their clearly demonstrated safety and effectiveness, approved vaccines against COVID-19 are commonly mistrusted. Nations should find and implement effective ways to boost vaccine confidence. But the implications for ethical vaccine development are less straightforward than some have assumed. Opponents of COVID-19 vaccine challenge trials, in particular, made speculative or empirically implausible warnings on this matter, some of which, if applied consistently, would have ruled out most COVID-19 vaccine trials and many non-pharmaceutical responses.

Worries about safety of approved drugs have pushed post registration research to become the fastest growing drug research phase. Until recently, phase IV studies were mainly conducted for marketing purposes and run much like a phase III trial—at institutions with experienced investigators and a list of inclusion and exclusion criteria. Innovative phase IV studies involve ordinary physicians in research naïve communities. This brings ethical issues familiar to medical research into clinical practice. As a consequence, individual physicians are challenged to (...) protect scientific integrity and to secure the ethical conduct of research. Several ethical issues need to be addressed in the process of developing a scientifically sound and ethically high principled practice of phase IV research.PHASE IVEssential to phase IV research is the focus on how drugs work in the real world. The research goal may be to explore a specific pharmacological effect, to establish the incidence of adverse reactions, or to determine the effects of long-term administration of a drug. They may also be designed to establish a new clinical indication for a drug.1 Subjects may or may not be randomised, and the studies typically involve large numbers of patient-subjects and physicians.Doubts concerning the scientific rigor and clinical value have put postmarketing research in a poor light. However, high quality phase IV research is badly needed to further pharmaceutical science. First, because it can provide reliable data on the effectiveness, safety and optimal use of a drug in treated populations.2 3 In pre-registration clinical trials , a pharmaceutical product is studied under unrealistic circumstances. Under-representation of women and elderly are common and the concomitant use of medicines is usually extremely restrictive in these trials.4 Second, phase IV can provide much needed data for evidence-based …. (shrink)

The number and the scale of transboundary public health concerns are increasing. Infectious and non-communicable diseases, international trade in tobacco, alcohol, and other dangerous products as well as the control of the safety of health services, pharmaceuticals, and food are merely a few examples of contemporary transnationalization of health concerns. The rapid development and diffusion of scientific and technological developments across national borders are creating new realms of international health concern, such as aspects of biomedical science, including human reproductive (...) cloning, germ-line therapy, and xenotransplantation, as well as environmental health problems, including climate change, biodiversity loss, and depletion of the ozone layer. Growth in international trade and travel, in combination with population growth, has served to increase the frequency and intensity of health concerns bypassing or spilling over sovereign boundaries.Although health has traditionally been seen an area of limited multilateral cooperation, there is growing awareness that contemporary globalization has led to the proliferation of cross border determinants of health status and is undermining the capacity of nation states to protect health through domestic action alone. (shrink)

In the debate on the ethics of the non-medical use of pharmaceuticals for cognitive performance enhancement in healthy individuals there is a clear division between those who view “cognitive enhancement” as ethically unproblematic and those who see such practices as fraught with ethical problems. Yet another, more subtle issue, relates to the relevance and quality of the contribution of scholarly bioethics to this debate. More specifically, how have various forms of speculation, anticipatory ethics, and methods to predict scientific trends and (...) societal responses augmented or diminished this contribution? In this paper, we use the discussion of the ethics of cognitive enhancement to explore the positive and negative contribution of speculation in bioethics scholarship. First, we review and discuss how speculation has relied on different sets of assumptions regarding the non-medical use of stimulants, namely: terminology and framing; scientific aspects such as efficacy and safety; estimates of prevalence and consequent normalization; and the need for normative reflection and regulatory guidelines. Second, three methodological guideposts are proposed to alleviate some of the pitfalls of speculation: acknowledge assumptions more explicitly and identify the value attributed to assumptions; validate assumptions with interdisciplinary literature; and adopt a broad perspective to promote more comprehensive reflection. We conclude that, through the examination of the controversy about cognitive enhancement, we can employ these methodological guideposts to enhance the value of contributions from bioethics and minimize potential epistemic and practical pitfalls in this case and perhaps in other areas of bioethical debate. (shrink)

Neuroethics entails investigations of neurocognitive mechanisms of morality and ethics; and studies and address of the ethical issues spawned by the use of neuroscience and its technologies to investigate cognition, emotion and actions. These two principal emphases, or what have been called “traditions” of neuroethics both mirror traditional bioethical discussions (such as debates about the safety of technological and pharmaceutical advances and ethical implications of new scientific and technological discoveries), and engage discourse about neuroscientific investigations of (proto-moral and (...) moral) cognition, emotions and behaviors, and what such findings may mean for human beliefs and conduct - from the individual to the political levels. (shrink)

Developments in neuroscience have raised the possibility that pharmaceuticals may be used to enhance memory, mood, and attention in people who do not have an illness or disorder, a practice known as “cognitive enhancement.” We describe historical experiences with two medicinal drugs for which similar enhancement claims were made, cocaine in the late 19th and early 20th centuries, and amphetamines in the mid 20th century. These drugs were initially introduced as medicinal agents in Europe and North America before becoming more (...) widely used for a variety of purposes, including what would nowadays be considered cognitive enhancement. Their trajectory of use conformed to the typical use cycle of psychotropic drugs. There was an initial steep rise in prescribing for medical use, followed by expanded nonmedical use that was fueled by enthusiasm for the drugs’ effects. As the number of regular users increased, problems related to use (such as addiction) became apparent, societal concern increased, and laws were passed banning nonmedical use and eventually, medical use. This historical experience draws attention to the adverse side effects of enhancement use that only become apparent with regular, wide-scale use of a drug. We highlight the similarities between the enthusiasms for cocaine and amphetamines and the current enthusiasms for using prescription stimulants for cognitive enhancement. We argue bioethicists should not encourage the cognitive enhancement use of drugs such as methylphenidate in the absence of evidence on the efficacy and safety of their use for cognitive enhancement purposes. (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)

As things stand today, whether we like it or not, industry funding is on the upswing. The whole enterprise of medicine in booming, and it makes sense for industry to invest more and more of one's millions into it. The pharmaceutical industry has become the single largest direct funding agency of medical research in countries like Canada, the United Kingdom and the United States. Since the goals of industry and academia differ, it seems that conflicts of interest are inevitable (...) at times. The crucial decision is whether the public welfare agenda of academia, or the corporate research agenda of industry, should occupy center stage when they conflict. There is enough evidence to show that funding by industry is very systematic, and results that are supportive of the safety and efficacy of sponsor's products alone get the funds. It is no surprise, therefore, that one finds very few negative drug trials reports published, and whatever are, are likely to be by rival companies to serve their commercial interests. Renewed and continued funding by industry decides the future prospects of many academic researchers. At the same time there is now evidence that pharmaceutical companies attempt suppression of research findings, may be selective in publishing results, and may delay or stymie publication of unfavourable results. This is a major area of concern for all conscientious researchers and industry watchers. Industry commonly decides which clinical research/trial gets done, not academia, much though the latter may wish to believe otherwise. It finds willing researchers to carry this out. This can be one area of concern. Another area of pressing concern is when industry decides to both design and control publication of research. It makes sense for researchers to refuse to allow commercial interests to rule research reporting. Research having been reported, the commercial implications of such reporting is industry's concern. But, doctoring of findings to suit commerce is to be resisted at all costs. In this even pliant researchers need have no fear, for if they indeed publish what will work, the concerned sponsor will benefit in the long run. The only decision academia has to make is refuse to comply with predestined conclusions of sponsors for the 'thirty pieces of silver'. Instead do genuine research and make sixty for themselves. The useful rule of thumb is: Keep the critical antenna on, especially with regard to drug trials, and more especially their methodology, and study closely the conflict of interest disclosed, and if possible undisclosed, before you jump on the band wagon to herald the next great wonder drug. There are three important lessons to be learnt by academia in all academia-industry relationships: i) Lesson number one: incorporate the right to publish contrary findings in the research contract itself. Which means, it makes great sense for academia to concentrate on the language and contractual provisions of sponsored research, to read the fine print very closely, and protect their research interests in case of conflict. ii) Lesson number two: a number of lawsuits successfully brought up against industry recently reflect earnest attempts by patient welfare bodies and others to remedy the tilt. It will result in a newfound confidence in academia that augurs well for academia industry relationship in the long run. Hence the second lesson for academia: do not get browbeaten by threats of legal action iii) Lesson number three: Academia should keep itself involved right from inception of the clinical trial through to ultimate publication. And this must be an integral part of the written contract. The time to repeat cliches about the exciting future of the academia-industry connect is past. A concerted effort to lay a strong foundation of the relationship on practical ethical grounds has become mandatory. (shrink)

Research drawn from data contained in medical records is a common and immensely important means of scientific investigation in epidemiology and health services research. It provides valuable knowledge regarding risk factors for disease, the safety of pharmaceuticals and medical procedures, and the quality of medical care. Electronic information technology has greatly enhanced the capability of conducting research using medical records, but it has also generated increasing concern about invasions of privacy. Both practical and scientific considerations militate against soliciting consent (...) for population-based observational research. Retrospective review of existing medical records, especially with large samples, poses insuperable barriers to locating human subjects in order to obtain their informed consent. When efforts are made to obtain informed consent for prospective research drawn from disease and treatment registries, mounting evidence has accumulated that substantial selection biases are introduced into the data, as those who consent are not necessarily representative of the population of relevant patients. (shrink)

The most recent (Fifth) revision of the Declaration of Helsinki, adopted in October 2000 by the World Medical Association (WMA), reinforces the longstanding prohibition against offering placebo instead of effective therapy. The WMA left no doubt that if a beneficial treatment for a condition has already been recognised, it is unethical to offer placebo in place of such treatment to anyone in a study of the same condition. We have previously drawn attention to the discrepancy between the spirit of the (...) Declaration and the common practice of using placebo controls in randomised trials even if effective treatment exists. Despite the mandates of the Declaration of Helsinki and concern from ethicists and scientists, the US Food and Drug Administration (FDA) continues to demand and defend placebo‐controlled evidence of efficacy and safety for the development of many new pharmaceuticals, even if effective therapy exists. We suggest that the FDA's arguments defending their practice are insufficient to justify medical research that violates the Declaration of Helsinki. (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)

One of the most fascinating issues in the emerging field of neuroethics is pharmaceutical cognitive enhancement. The three main ethical concerns around CE were identified in a Nature commentary in 2008 as safety, coercion and fairness; debate has largely focused on the potential to help those who are cognitively disabled, and on the issue of ‘cosmetic neurology’, where people enhance not because of a medical need, but because they want to. However, the potential for CE to improve public (...) health has been neglected. This paper examines the prospect of improving health outcomes through CE among sections of the population where health inequalities are particularly pronounced. I term this enhancement of the public’s health through CE ‘neuroenhancing health’. It holds great promise, but raises several ethical issues. This paper provides an outline of these issues and related philosophical problems. These include the potential effectiveness of CE in reducing health inequalities; issues concerning autonomy and free will; whether moral enhancement might be more effective than CE in reducing health inequalities; and the problem of how to provide such CE, including the issue of whether to provide targeted or universal coverage. (shrink)