SummaryThis article documents understandings and responses to mass drug administration for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive (...) or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment ; divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side – adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal. (shrink)

The process of risk assessment of biotechnologies, such as genetically modified organisms (GMOs), has normative dimensions. However, the US’ Food and Drug Administration (FDA) seems committed to the idea that such evaluations are objective. This essay makes the case that the agency’s regulatory approach should be changed such that the public is involved in deciding any ethical or social questions that might arise during risk assessment of GMOs. It is argued that, in the US, neither aggregative nor deliberative (...) (representative) democracy ought to be used to make such determinations. Instead, participatory (deliberative) democracy should be the means by which members of the polity decide which normative concerns ought to underlie FDA’s assessment of GMOs. This paper uses a hypothetical case involving a new GM seed to make that argument. (shrink)

In The Ethics of Food, Gregory E. Pence brings together a collection of voices who share the view that the ethics of genetically modified food is among the most pressing societal questions of our time. This comprehensive collection addresses a broad range of subjects, including the meaning of food, moral analyses of vegetarianism and starvation, the safety and environmental risks of genetically modified food, issues of global food politics and the food industry, and the relationships among food, evolution, and human (...) history. (shrink)

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

People in the bioethics field generally agree that clinicians should have reasonable freedom to practice according to their moral and religious convictions. But this general position leaves room for debate over how much freedom objecting clinicians ought to have. Some commentators contend that exemptions from criminal, civil, and professional consequences for conscientious refusals to provide care impose too many burdens on patients, colleagues, and health care institutions. Others argue that existing protections are insufficient, failing to cover clinicians who are moved (...) to provide legally permitted care to patients in the face of institutional and employment constraints on doing so. A 2024 United States Supreme Court ruling adds another element to the debate, showing how conscience-law protections can defeat legal efforts to limit access to contested treatments. (shrink)

We investigate how and under what conditions perceived wrongdoing of a government organization (i.e., The Food and Drug Administration) leads to mistrust and other negative reactions to the institution. The “how” questions were addressed by specifying a model drawing upon two theories from moral psychology: the social intuitionist model (Haidt, The righteous mind: Why good people are divided by politics and religion, Vintage, 2012) and the theory of dyadic morality (Schein and Gray, Personality and Social Psychology Review 22:32–70, (...) 2018). Our integration of these two theories proposes that consumer reactions to perceived institutional wrongdoing are serially mediated by contempt, anger, and disgust and by the likelihood of possible harm to them. The “when” question (i.e., the conditions under which negative reactions arise) was addressed by drawing upon moral identity theory, whereby we hypothesized that perceived organizational wrongdoing influences negative moral emotions and harm to the extent that people have a strong personal moral identity (Aquino et al., Journal of Personality and Social Psychology 97:123–141, 2009; Blasi, A. (2004). Moral functioning: Moral understanding and personality, U: Moral development, self and identity, ur. Lapsley, Daniel K. i Darcia, Narvaez, Mahwah, 335–347.). Hypotheses are tested on a random sample of 204 U.S. adults. Policy implications are discussed. The results suggest that government organizations such as the Food and Drug Administration need to better communicate with their constituents about their value to them. For example, the FDA should provide cases of how they promote safe medication use that protect the consumers from harm. (shrink)

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

The U.S. Food and Drug Administration (FDA) announced recently that food products derived from some animal clones and their offspring are safe for human consumption. In response to criticism that it had failed to engage with ethical, social, and economic concerns raised by livestock cloning, the FDA argued that addressing normative issues prior to issuing a final ruling on animal cloning is not part of its mission. In this article, the authors reject the FDA's claim that its mission (...) to protect and advance public health can be accomplished without considering ethical issues or without making value judgments. The authors offer two arguments in support of their position. First, the agency's mission statement presupposes significant normative commitments and judgments. Second, the FDA's risk assessment of food products from cloned animals and their offspring is itself clearly shaped by a variety of normative commitments. (shrink)

The US Food and Drug Administration (FDA) issues warning letters to all research stakeholders if unacceptable deficiencies are found during site visits. Warning letters issued by the FDA between January 2011 and December 2012 to clinical investigators and institutional review boards (IRBs) were reviewed for various violation themes and compared to similar studies in the past. Warning letters issued to sponsors between January 2005 and December 2012 were analysed for the first time for a specific set of violations (...) using descriptive statistics. Failure to protect subject safety and to report adverse events to IRBs was found to be significant compared to prior studies for clinical investigators, while failure to follow standard operating procedures and maintain documentation was noted as significant in warning letters to IRBs. Failure to maintain minutes of meeting and to follow written procedures for continuing review were new substantial violations in warning letters issued to IRBs. Forty-six warning letters were issued to sponsors, the most common violations being failure to follow a monitoring schedule (58.69%), failure to obtain investigator agreement (34.78%), failure to secure investigators’ compliance (30.43%), and failure to maintain data records and ship documents to investigators (30.43%). Appropriate methods for handling clinical trial procedural violations should be developed and implemented worldwide. (shrink)

The U.S. Food and Drug Administration's rationale for supporting the development and approval of BiDil for heart failure specifically in black patients was based on under-powered, post hoc subgroup analyses of two relatively old trials , which were further complicated by substantial covariate imbalances between racial groups. Indeed, the only statistically significant difference observed between black and white patients was found without any adjustment for potential confounders in samples that were unlikely to have been adequately randomized. Meanwhile, because (...) the accepted baseline therapy for heart failure has substantially improved since these trials took place, their results cannot be combined with data from the more recent trial amongst black patients alone. There is therefore little scientific evidence to support the approval of BiDil only for use in black patients, and the FDA's rationale fails to consider the ethical consequences of recognizing racial categories as valid markers of innate biological difference, and permitting the development of group-specific therapies that are subject to commercial incentives rather than scientific evidence or therapeutic imperatives. This paper reviews the limitations in the scientific evidence used to support the approval of BiDil only for use in black patients; calls for further analysis of the V-HeFT I and II data which might clarify whether responses to H-I vary by race; and evaluates the consequences of commercial incentives to develop racialized medicines. We recommend that the FDA revise the procedures they use to examine applications for race-based therapies to ensure that these are based on robust scientific claims and do not undermine the aims of the 1992 Revitalization Act. (shrink)

The clinical Bioresearch Monitoring (BIMO) oversight program of the US Food and Drug Administration (FDA) assesses the quality and integrity of data submitted to the FDA for new product approvals and human subjects protection during clinical studies. A comprehensive program of on-site inspections and data verification, the BIMO program routinely performs random inspections to verify studies submitted to the FDA to support a marketing application. On occasion the FDA will conduct a directed inspection of a specific site or (...) study to look for problems that may have previously been identified. The inspection of a clinical study sometimes uncovers evidence of research fraud or misconduct and it must be decided how to deal with the investigator and the suspect data. The prevention of [or] decreasing the incidence of fraud and misconduct through monitoring by the sponsor is one way to manage compliance issues and can help prevent misconduct. A training program is another way to manage compliance issues in clinical research. While training does not guarantee quality, it does help to ensure that all individuals involved understand the rules and the consequences of research misconduct. (shrink)

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

Evolving medical research and treatment modalities have been channeled into safe and effective therapies for the welfare of the public by means of laws and regulations and their periodic modernizations. A regulated environment also creates a fair place for industry stakeholders to compete. The United States Food and Drug Administration as well as Health Canada, both federal agencies, have been instrumental in bringing new therapies to their respective countries. The granularity of regulations, need for evidence, and associated costs (...) increase as the risks associated with the use of these products increase, with prescription drugs being the most challenging and cosmetics being the least. The International Conference on Harmonization made it possible for countries to develop common guidelines, and for the industry to submit mostly the same dossier to multiple countries. Getting an approval to sell a drug is the start of a journey of continuing compliance and demonstration of adherence to the country’s laws and regulations. (shrink)

Background U.S. federal regulations require that certain ethical elements be followed to protect human research subjects. The location and clinical circumstances of a proposed research study can differ substantially and can have significant implications for these ethical considerations. Both the location and clinical circumstances are particularly relevant for research in intensive care units (ICUs), where patients are often unable to provide informed consent to participate in a proposed research intervention. Purpose Our goal is to elaborate on the updated 2013 U.S. (...) Food and Drug Administration (FDA) guidance document regarding an exemption from the requirement of obtaining informed consent from patients or their surrogates and to address certain elements within that document, thereby assisting clinicians in developing a framework for emergency research in accordance with the regulatory bodies at their own institutions and in the United States. Methods Review of the 2011 and updated FDA guidance document on exemption from informed consent. Results The current process of obtaining informed consent within ICUs needs to be revisited, especially for research in which timely informed consent is not likely. In particular, the process of obtaining informed consent may not be appropriate or even ethical for critically ill patients in extremis who require an intervention for which there is no current acceptable standard of care and clinical equipoise exists. We provide clinicians with a viewpoint that further elaborates on the FDA guidance document. Limitations The viewpoints provided herein are those of the authors and are therefore inherently limited by the personal views of a selected few. Other clinicians or researchers may not interpret the FDA guidelines in a similar manner. Moreover, the discussion of a guideline document is a limitation in and of itself. The guidelines set forth by the FDA are precisely that—guidelines. Therefore, they may not be followed as outlined in the guidance document within one’s own institution. Our goal is that, by elaborating on the guidelines for planned research involving human subjects in the ICU, institutional regulatory bodies may gain a better understanding in drafting their own document when faced with a clinician or a researcher who wishes to conduct planned research in an ICU. Conclusions We believe that the interpretations provided will allow clinicians to safely undertake planned research in ICUs without endangering the main tenets of ethical research involving human participants. This research is needed for the advancement of care in the critically ill. (shrink)

Given the profound public health and economic ramifications of decisions made by the U.S. Food and Drug Administration, the degree to which FDA activities should reflect an approach founded on complete transparency versus one focused on preserving confidentiality of information deserves public discussion. On one hand, reasonable requirements for transparency are critical to stimulating effective innovation, knowledge dissemination, and good business practice. On the other, ensuring the vitality of the medical products industry requires protecting legitimately proprietary information. With (...) current standards reflecting a lengthy accumulation of legal, regulatory, and practical precedent, recent significant changes in the environment in which the FDA operates should prompt a critical examination of current practices. In this article, I comment on Sharfstein and colleagues’ “Blueprint for Transparency,” which calls for multiple specific actions to increase transparency at the agency across five key areas, including interactions between FDA and industry, public disclosure of internal FDA analyses, deliberations concerning generics and biosimilars, expanded access to raw study data, and approaches to countering misleading information in the public sphere. I evaluate these recommendations in light of my experience as a clinician, researcher, and former FDA Commissioner, and reflect on possible outcomes that could result from enacting these practices. (shrink)

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

Drug recalls and lawsuits against pharmaceutical manufacturers are accompanied by announcements emphasizing harmful drug side-effects. Those with elevated health anxiety may be more reactive to such announcements. We evaluated whether health anxiety and financial incentives affect subjective symptom endorsement, and objective outcomes of cognitive and physiological functioning during a mock drug recall. Hundred and sixty-one participants reported use of over-the-counter pain medications and presented with a fictitious medication recall via a mock Food and Drug Administration (...) website. The opportunity to join a class-action lawsuit was manipulated. We assessed health anxiety, recalled drug usage, blood pressure, heart rate, and performance on a computerized Trail Making Test. Symptom endorsement was strongly predicted by health anxiety. When combined, three health anxiety measures explained 28.5% variance. These effects remain strong after controlling for depression and anxiety. Litigation condition did not predict symptom endorsement. Blood pressure and heart rate were modestly predicted by health anxiety, but not by litigation condition. TMT performance was consistently predicted by health anxiety, with higher scores associated with poorer performance. Although there were no main effects for litigation, interactions consistently emerged for the TMT, with generally poorer performance for those with higher health anxiety in the non-litigation condition; whereas health anxiety was unrelated to performance for the litigation condition. All but one participant joined the litigation when given the opportunity, despite a healthy sample and minimal use of pain medication. Subsequent data from 67 individuals with no mention of the FDA scenario or litigation showed that health anxiety still significantly predicts symptom endorsement, but the explained variance is less than half that obtained in the FDA scenario. The findings suggest that health anxiety plays a significant role in adverse symptom reporting, beyond anxiety or depression, and this effect is independent of the presence of the FDA recall. The lack of differences for health anxiety and symptom endorsement between litigation and non-litigation conditions rules out malingering. Although it is general practice in drug recalls to list potential adverse side effects caused by medications, this may elicit unintended symptom experiences and health anxious individuals may be more susceptible. (shrink)

Federal regulations are the minimum requirements for conducting clinical studies. Some innovation would improve the situation of many involved in these studies, including: study subjects, those who monitor studies, and clinical investigators as well as Institutional Review Boards. Respecting patient and whistle-blower input; appreciating research staff contributions; and implementing a systems and partnership approach would foster quality and advance clinical research.

The suitability of doctors as agents of assisting dying remains debated, although it is common in many jurisdictions, and forms part of the proposed assisted dying legislation for England and Wales. We examine the established philosophical and legal role of doctors in England and Wales and compare it to the active role required of doctors under proposed assisted dying legislation. For clarity, we refer to the latter role as ‘assisted dying practitioner’ (ADP). We interrogate two common claims: that (a) the (...) role of doctors and ADPs holds normative conceptual analogy by virtue of shared goals to uphold autonomy and reduce suffering and (b) the practical skills required of ADPs are specific and exclusive to a doctor’s training. Examination reveals that neither claim is justified and, despite both roles prioritising patient welfare, identifies significant conflict between their primary goals. The role of an ADP is philosophically and legally singular. To add a duty to the role of the doctor which is antithetical to their overall goal of cure and disease prevention disrupts the defining characteristic of being a doctor: this may have repercussions on who applies to medicine, how doctors are trained, interact with patients and are regulated. We do not advocate for or against assisted dying but propose that if it is to be taken forward in England and Wales, society would be more appropriately served by considering the role of an ADP as a novel profession whose goals, competencies, research base and regulation can be established independently. (shrink)

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

Patients’ admission to modern substance use disorder treatment comes with the attendant risk of being discharged from treatment— a widespread practice. This article describes the three mainstream theories of addiction that operate as a reference point for clinicians in reasoning about a decision to discharge a patient from treatment. The extant literature is reviewed to highlight the pathways that patients follow after administrative discharge. Little scientific research has been done to investigate claims and hypotheses about the therapeutic function of AD, (...) which points to the need for empirical ethics to inform clinical addictions practice. (shrink)

Among American adults 20 years and older, 59 percent take at least one prescription drug on a regular basis. Unlike most branded drugs, which are generally drugs that have a trade name and are protected by a patent, off‐patent generic drugs make up approximately 90 percent of prescriptions annually filled in the United States; yet in 2017, generic drugs made up only 23 percent of total drug costs in the U.S. The U.S. Food and Drug Administration (...) has taken the lead in encouraging increased competition in the nation's prescription drug marketplace, most recently with its release of the agency's Drug Competition Action Plan, but also with its regulatory guidance and enforcement efforts to eliminate “gaming” of the regulatory process by both branded and generic pharmaceutical manufacturers. Such “gaming” activities include “pay‐for‐delay” agreements involving financial compensation between branded and generic pharmaceutical manufacturers to forestall the emergence into the market of generic pharmaceuticals to compete against a formerly patent‐protected branded drug. A combination of new enabling legislation, federal judicial guidance, and agency regulatory activities show promise in encouraging increased competition in the prescription drug marketplace, with the American consumer the ultimate beneficiary of lower health care costs and improved overall personal health. (shrink)

During the process of in vitro fertilization (IVF), hormonal drugs are used to stimulate the woman's ovaries to produce multiple eggs. The injecting of the drugs is often performed by the women themselves outside of the clinical context, constituting a gendered burden of work that is rendered invisible by the dominant representations of treatment as undergone by couples and performed by doctors. Based on a series of interviews with women and couples who have undergone IVF unsuccessfully and who have ended (...) treatment at least two years previously, this paper focuses on two aspects of the self-injection of hormonal drugs that emerged from the participants accounts: firstly, the gendered ways in which the drug regimen was experienced as compromising privacy and secondly, the strategic use of images of both illicit and medical drug use in the accounts. The paper argues that in spite of the dominant representation of IVF as a couples’ technology, the IVF process is profoundly gendered, both in terms of bodily intervention and in the distribution of labour in the implementation of treatment; that the invisibility of the drug regimens from dominant representations of IVF can leave those undergoing treatment unprepared for some of the problems that the self-administration of the drugs can raise, particularly in terms of maintaining privacy; and finally, that images of the drug injection are mobilized strategically in the accounts to locate themselves within normative social reproductive standards. This highlights the extent to which the enduring ideological construction of proper womanhood as defined by motherhood continues to pose a dilemma for those who are involuntarily childless. (shrink)

Genetically engineered animals that are meant for release in the wild could significantly impact ecosystems given the interwoven or entangled existence of species. Therefore, among other things, it is all too important that regulatory agencies conduct entity appropriate, rigorous risk assessments that can be used for informed decision-making at the local, national and global levels about the release of those animals in the wild. In the United States, certain GE animals that are intended for release in the wild may be (...) regulated as new animal drugs by the Food and Drug Administration. This paper argues that the decision to treat them as new animal drugs is attributable to the influence of neoliberalism on the US biotechnology regulatory policy framework. The case is made that there should be public democratic deliberations and decision-making about the values and concerns that should guide the nation’s biotechnology regulatory policy paradigm, including the risk assessment process for GE animals meant for release in the wild. -/- . (shrink)

Objective To assess whether the frequency of end-of-life decisions for children under 1 year of age in the Netherlands has changed since ultrasound examination around 20 weeks of gestation became routine in 2007 and after a legal provision for deliberately ending the life of a newborn was set up that same year. Methodology This was a recurrent nationwide cross-sectional study in the Netherlands. In 2010, a sample of death certificates from children under 1 year of age was derived from the (...) central death registry. All 223 deaths that occurred in a 4-month study period were included. Physicians who had reported a non-sudden death (n=206) were sent a questionnaire on the end-of-life decisions made. 160 questionnaires were returned (response 78%). Findings In 2010, 63% of all deaths of children under 1 year of age were preceded by an end-of-life decision—a percentage comparable to other times when this study was conducted (1995, 2001, 2005). These end-of-life decisions were mainly decisions to withdraw or withhold potentially life-sustaining treatment. In 2010, the percentage of cases in which drugs were administered with the explicit intention to hasten death was 1%, while in 1995 and 2001, this was 9% and in 2005, this was 8%. Discussion and conclusion There has been a reduction of infant deaths that followed administration of drugs with the explicit intention to hasten death. One explanation for this reduction relates to the introduction of routine ultrasound examination around 20 weeks of gestation. In addition, the introduction of legal criteria and a review process for deliberately ending the life of a newborn may have left Dutch physicians with less room to hasten death. (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)

Caffeine, a known CNS stimulant is given as an adjunct component in most abused drugs which could be fatal with repeated administration in many circumstances. This paper presents a study to investigate the effect of repeated administration of caffeine at high dose on rat liver, and discusses ethical and policy issues of caffeine use. Long Evans rats were treated with pure caffeine solution in distilled water through intragastric route once daily for consecutive 56 days. Three groups of rats (...) recognized as low dose, high dose and control group received 6mg caffeine / kg BW, 12mg caffeine / kg BW and distilled water, respectively. Rat plasma was examined for liver transaminases and alkaline phosphatases concentrations which were significantly increased in plasma as compared to the control. Both rat plasma and liver homogenate were subjected to estimate malondialdehyde, advanced oxidation protein product, nitric oxide, antioxidant enzyme catalase, glutathione and superoxide dismutase activity. MDA, AOPP, NO levels increased and SOD activity decreased significantly in both plasma and liver as compared to those of control where as CAT and GSH activity remain unchanged. Rat liver tissues were studied histochemically with Hematoxylin and Eosin, and Picro Sirius Red staining. Significantly increased infiltration of inflammatory cells and progressive deposition of collagen fibre were visible in liver tissue of caffeine treated both dose groups as compared to the control. Long term administration of caffeine at higher dose, significantly contributes to liver inflammation and consequent fibrogenesis. This raises significant ethical and policy issues. (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)

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

The agencies of the government of the United States of America, such as the Food and Drug Administration or the Environmental Protection Agency, intervene in American society through the collection, processing, and diffusion of information. The Presidency of Barack Obama was notable for updating and redesigning the US government’s information infrastructure. The White House enhanced mass consultation through open government and big data initiatives to evaluate policy effectiveness, and it launched new ways of communicating with the citizenry. In (...) this essay we argue that these programs spelled out an emergent epistemology based on two assumptions: dispersed knowledge and a critique of judgment. These programs have redefined the evidence required to justify and design regulatory policy and conferred authority to a new kind of expert, which we call epistemic consultants. (shrink)

The Food and Drug Administration, as a matter of long-standing policy, does not inform the public of instances whereby applications for new drugs or new indications for existing drugs have been rejected by the agency or withdrawn from consideration, nor does it disclose the agency’s analyses of the data submitted with such applications. This lack of transparency is unjustified and prevents patients, researchers, and healthcare providers from gaining insight into why a drug’s application was not approved. The (...) FDA’s policy is particularly troubling in cases where the agency has found a currently marketed drug to be ineffective or unsafe for a newly proposed indication. Disclosure of the FDA’s findings in such cases would promote public health by encouraging healthcare providers to avoid prescribing drugs for unapproved uses that the agency has deemed to be potentially dangerous or ineffective. The FDA’s counterpart agencies in Europe and Canada have demonstrated the feasibility of disclosing information on rejected and withdrawn drug marketing applications. The FDA should follow suit and allow the American public to know when a drug is deemed unsafe or ineffective for a certain use. (shrink)

Clinical pharmacology deals with the pharmacokinetics and pharmacodynamics of various drugs acting in the human system. In pregnancy and lactation, marked physiological variations affect the drug response with a special concern on fetal teratogenesis. Thus, the drugs must be used cautiously in pregnancy, lactation, and in women with childbearing potential. A considerable challenge is faced due to the paucity of available data, as pregnant and lactating women are excluded from most drug trials. The medications must be prescribed keeping (...) in mind the risk vs benefit of the drug administration to the women. Also, the drugs should not be withheld due to their teratogenic effect, during life-threatening emergencies or serious illness to the mother. Hence, the art of drug prescribing in the perinatal period needs careful clinical discretion and a complete understanding of perinatal pharmacology. This chapter gives a bird’s eye view of drug use in pregnancy and lactation. (shrink)

In 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)

Assume this hypothetical situation: an American pharmaceutical company, Maxwell Fisch Pharmaceuticals, Inc., wishes to perform clinical trials involving a new antipsychotic medication, Klezac. Klezac is in its third phase of the clinical stage of the drug research process. Once the testing is complete, Maxwell plans to submit a New Drug Application, the official request to begin marketing Klezac, to the Food and Drug Administration. The new drug is expected to receive FDA approval in 2 or (...) more years. The company decides to shift its research and development activities to Z, a small, developing country. In doing so, Maxwell is following the course taken by numerous other drug companies who wish to take advantage of faster governmental approval in foreign sites and ensuing cheaper research costs. (shrink)

In September 2012, news broke of a developing drug disaster in the United States. Health authorities had linked a fungal meningitis outbreak to a contaminated steroid made by a company called the New England Compounding Center. The contaminated steroid was a compounded drug that had not been approved by the Food and Drug Administration, differing from three others that had been approved in that it lacked preservatives present in those agents. Factory inspections revealed unsanitary conditions at (...) NECC's drug production facility. By the time the source of the outbreak was identified, an estimated fourteen thousand people had been injected with the drug. As of December 2012, thirty‐nine had died of meningitis, and hundreds more had been diagnosed with meningitis and other drug‐related conditions. Many factors contributed to this disaster. One was a 2002 Supreme Court decision holding that a law prohibiting providers of compounded drugs from promoting their products through advertising and other means impermissibly restricted commercial speech. (shrink)

Despite some improvements in access to evidence-based medications for opioid use disorder, treatment rates remain low at under a quarter of those with need. High costs for brand name products in these medication markets have limited the volume of drugs purchased, particularly through public health insurance and grant programs. Brand firm anti-competitive practices around the leading buprenorphine product Suboxone — including product hops, citizen petitions and Risk Evaluation and Mitigation Strategy abuses — helped to maintain high prices by extending brand (...) exclusivity periods and hindering generic drug entry. Remedies to address costly anti-competitive activities include adoption of the proposed CREATES Act and modernization of the Hatch-Waxman Act by the Congress, and implementation of substantive modifications to the Food and Drug Administration citizen petition filing procedures. Given the persistence of these abuses, prescriptive changes are favorable to the procedural and clarifying steps thus far favored by the federal government. Extrapolating from the 37% price declines attributable to generic entry for buprenorphine tablets in 2011, our calculations suggest that implementing these remedies to facilitate generic competition with Suboxone film would have resulted in savings of approximately $703 million overall and $203 million to Medicaid in 2017. (shrink)

Marion Lee Sanders,1 Anthony James Langone2 1Department of Medicine, Division of Nephrology and Hypertension, University of Iowa, Iowa City, IA, 2Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA: Transplantation is the preferred treatment option for individuals with end-stage renal disease. Individuals who undergo transplantation must chronically be maintained on an immunosuppression regimen for rejection prophylaxis to help ensure graft survival. Current rejection prophylaxis consists of using a combination of calcineurin inhibitors, mTOR inhibitors, antimetabolite (...) agents, and/or corticosteroids. These agents have collectively improved the short-term outcomes of renal transplantation, but improvements in late/chronic graft loss and recipient survival have lagged significantly behind challenging the field of transplantation to develop novel prophylactic agents. There have been several clinical trials conducted within the last 5 years in an attempt to bring such novel agents to the commercial market. These trials have resulted in the US Food and Drug Administration approval of extended-release tacrolimus, as well as belatacept, which has the potential to replace calcineurin inhibitors for rejection prophylaxis. Other trials have focused on the development of novel calcineurin inhibitors, costimulation blockade, kinase inhibitors, and inhibitors of leukocyte migration. While these later agents have not been FDA-approved for use in transplantation, they remain noteworthy, as these agents explore pathways not previously targeted for allograft-rejection prophylaxis. The purpose of this review was to consolidate available clinical trial data with regard to the recent developments in rejection prophylaxis in kidney transplantation. Keywords: rejection, prophylaxis, immunosuppression, transplantation. (shrink)

In February, the Food and Drug Administration announced a rule imposing new manufacturer labeling requirements for antibiotics. The aim of the new standards is to educate physicians and patients about the dangers of improper antibiotic use. Overprescription of antibiotics, as well as patient failure to comply with treatment regimens, has led to the development of drug-resistant bacteria. “Antibacterial resistance is a serious and growing public health problem in the United States and worldwide,” FDA Commissioner Mark McClellan said (...) in a press release accompanying the rule. “Without effective antibiotic drugs, common infections, that were once easily treated, can create a serious health threat to children and adults alike.”The FDA regulates foods, drugs, and cosmetics introduced into interstate commerce for safety and effectiveness. Currently, the agency requires drug labels to provide “adequate directions for use,” including indications, quantity of dose, frequency, duration, route, and preparation. (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)

On April 6, 2000, Dr. J. Craig Venter of Celera Genomics told a Congressional committee that his company finished its analysis of the human DNA and would have a completed map of the human genome by early summer, 2000. Scientists expect the completed human genome to revolutionize drug therapies through the creation of treatments tailored to specific genetic makeups. In order to create a map of the human genome, three billion letters of DNA that encode eighty thousand genes must (...) be identified and ordered. In March, 2000, Celera released a successful sequence of the fruit fly genome, and it employed the same methods in creating the human genome. (shrink)

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