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)

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)

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)

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

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)

BackgroundThe US Food and Drug Administration (FDA) regulates goods accounting for 20% of US consumers’ total expenditure. The agency’s potential susceptibility to corporate lobbying and political influence may adversely affect the its abilities to fulfill its duties as a vital federal agency. This study assesses whether the FDA’s product recall classifications in recall scenarios are influenced by firms’ lobbying activities.MethodsThe universe of all FDA recalls between 2012 and 2019 is obtained from the FDA’s website. Firm names are (...) matched to federal-level lobbying data obtained from the Center for Responsive Politics – a non-profit and nonpartisan organization that tracks lobbying expenditures and campaign contributions. Analyses are conducted using ordinary-least-squares regressions, in which the dependent variable is recall classification and independent variables are three different measures of firms’ lobbying activities in the one year prior to the recall.ResultsFirms that engage in lobbying appear more likely to receive favourable classifications from the FDA. When examining the above results by product type, we find that classification of food recalls seems to be subject to lobbying influence, but the same does not appear to be true for drug and device recalls. Evidence is consistent with the conjecture that the distinction between medical and food firms may be a result of medical firms targeting lobbying efforts at FDA approvals, rather than recalls.ConclusionsBetween 2012 and 2019, the FDA’s product recall classifications seem to be significantly influenced by firms’ lobbying activities. Lobbying firms appear to have received more favorable (i.e., less severe) recall classifications compared to non-lobbying firms. (shrink)

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

In March 2022 the US Food and Drug Administration (FDA) published a risk assessment of a recent animal gene editing proposal submitted by Acceligen™. The proposal concerned the possibility of changing the cattle genome to obtain a slicker, shorter hair coat. Using CRISPR-Cas9 it was possible to introduce an intentional genomic alteration (IGA) to the prolactin receptor gene (PRLR), thereby producing PRLR-SLICK cattle. The goal was to diminish heat stress in the cattle by enhancing their heat-tolerance. With (...) regard to unintended alterations (i.e., off-target effects), the FDA stated that the IGA posed a low, but still present, risk to animal safety. The aim of this article is to present some initial insights into the welfare issues raised by PRLR-SLICK cattle by addressing the question: Do SLICK cattle have better welfare than non-SLICK cattle when exposed to heat stress? Two potential welfare concerns are examined. The first is pleiotropy, an issue that arises when one gene affects multiple traits. Given the pleiotropic nature of prolactin, it has been suggested that the IGA for SLICK cattle may also affect their hepatic and other functions. The second concern relates not primarily to direct effects on cattle health, but rather to the indirect risk that this more heat-tolerant animal would just be used in the livestock sector under farming conditions that are such that the net welfare improvement would be non-existent. (shrink)

One of the most pressing issues that confronts the Food and Drug Administration (FDA) is learning how to better address and assist in medical product development. FDA needs to prepare today so the agency can efficiently evaluate the technologies of tomorrow. Clearly, this is an area that impacts not only health care consumers but also our economies and financial markets. If the FDA can be a more aggressive part of the solution, they can help not only ease (...) some of the pressures that are driving up health care costs but also help all of us to maximize the value of medical innovations. The high cost of research and development is forcing many companies to make the short-term business decision to focus product development on those molecules that have a much higher potential to recoup expenditures. Unfortunately, this trumps attempts to develop potentially risky but breakthrough products for diseases affecting smaller populations, the orphan drugs. FDA's critical path initiative will enable innovative growth companies to better and more efficiently attack the steep hurdles facing them, allowing them to compete more effectively against the bigger, better-funded players in the market on a more level playing field. That means a real change in the risk/benefit equation for both the emerging growth companies and the public health. (shrink)

Pharmaceutical paternalism is the normative stance upheld by pharmaceutical regulatory agencies like the US Food and Drug Administration. These agencies prevent patients from accessing treatments declared safe and ineffective for the patient’s good without their consent. Libertarian critics of the FDA have shown a number of significant flaws in regulatory paternalism. Against these objections, I will argue that, in order to make an informed decision about treatments, a libertarian patient should request full disclosure of the uncertainty about (...) an experimental treatment. But pharmaceutical markets, on their own, are not a reliable source of information about such uncertainty. And companies have the power to capture any independent expert who may assess it. Therefore, the libertarian is better off deferring on an independent regulatory body the assessment of the pharmaceutical risks, constraining access to treatments until tested. (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)

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 commentary defends 3 arguments for changing the label of levonorgestrel-based emergency contraception (LNG EC) so that it no longer supports the possibility of a mechanism of action after fertilization. First, there is no direct scientific evidence confirming any postfertilization mechanisms. Second, despite the weight of evidence, there is still widespread public misunderstanding over the mechanism of LNG EC. Third, this FDA label is not a value-free claim, but instead it has functioned like a political tool for reducing contraceptive access. (...) The label is laden with antiabortion values (even though EC is contraception, not abortion), and it imposes these values on potential users, resulting in barriers to access such as with Burwell v. Hobby Lobby. These 3 arguments together provide scientific, social, and ethical grounds for the FDA to take the initiate in changing Plan B's drug label. (shrink)

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

We agree with Svirsky, Howard, and Berman that the US Food and Drug Administration plays various roles, only one of which is the technical review and evaluation of product safety and e...

This paper examines the Saudi Food and Drug Authority’s (SFDA) Guidance on Artificial Intelligence (AI) and Machine Learning (ML) technologies based Medical Devices (the MDS-G010). The SFDA has pioneered binding requirements designed for manufacturers to obtain Medical Device Marketing Authorization. The regulation of AI in health is at an early stage worldwide. Therefore, it is critical to examine the scope and nature of the MDS-G010, its influences, and its future directions. It is argued that the guidance is a (...) patchwork of existing international best practices concerning AI regulation, incorporates adapted forms of non-AI-based guidelines, and builds on existing legal requirements in the SFDA’s existing regulatory architecture. There is particular congruence with the approaches of the US Food and Drug Administration (FDA) and the International Medical Device Regulators Forum (IMDRF), but the SFDA goes beyond those approaches to incorporate other best practices into its guidance. Additionally, the binding nature of the MDS-G010 is complex. There are binding ‘components’ within the guidance, but the incorporation of non-binding international best practices which are subordinate to national law results in a lack of clarity about how penalties for non-compliance will operate. (shrink)

Deep brain stimulation (DBS) has been regarded as an efficient and safe treatment for Parkinson’s disease (PD) since being approved by the Food and Drug Administration (FDA) in 1997. It is estimated that more than 150 000 patients have been implanted, with a forecasted rapid increase in uptake with population ageing. Recent longitudinal follow-up studies have reported a significant increase in postoperative survival rates of patients with PD implanted with DBS as compared with those not implanted with (...) DBS. Although DBS tends to increase life expectancy for most patients with PD, this medical benefit does not come without attendant negative consequences. For example, emerging forms of iatrogenic harms are sometimes induced—harms which were not initially expected when clinicians proposed neurosurgery and patients or their guardians consented to the treatment. We report and discuss the clinical case of a patient who was implanted with DBS more than 20 years ago (at the time of writing) and is now experiencing unexpected stages of PD. This case illustrates how extending the life span without improving quality of life may introduce a burden of harms for patients and families. As well, this case shows why we should prepare for the expanding numbers of PD-implanted patients experiencing a gain of longevity but with severe stages of disease leading to diminution in quality of life. This newly observed effect of DBS treatment requires us to explore ethical questions related to iatrogenic harms, informed consent, end of life and caregivers’ burden. (shrink)

Deep brain stimulation — a novel surgical procedure — is emerging as a treatment of last resort for people diagnosed with neuropsychiatric disorders such as severe obsessive-compulsive disorder. The US Food and Drug Administration granted a so-called humanitarian device exemption to allow patients to access this intervention, thereby removing the requirement for a clinical trial of the appropriate size and statistical power. Bypassing the rigors of such trials puts patients at risk, limits opportunities for scientific discovery, and (...) gives device manufacturers unique marketing opportunities. We argue that Congress and federal regulators should revisit the humanitarian device exemption to ensure that it is not used to sidestep careful research that can offer valuable data with appropriate patient safeguards. (shrink)

The ability of adolescents to access safe and effective new products for HIV prevention and treatment is optimised by adolescent licensure at the same time these products are approved and marketed for adults. Many adolescent product development programmes for HIV prevention or treatment products may proceed simultaneously with adult phase III development programmes. Appropriately implemented, this strategy is not expected to delay licensure as information regarding product efficacy can often be extrapolated from adults to adolescents, and pharmacokinetic properties of drugs (...) in adolescents are expected to be similar to those in adults. Finally, adolescents enrolled in therapeutic HIV prevention and treatment research can be considered adults, based on US Food and Drug Administration regulations and the appropriate application of state law. The FDA permits local jurisdictions to apply state and local HIV/sexually transmitted infection minor treatment laws so that adolescents who are HIV-positive or at risk of contracting HIV may be enrolled in therapeutic or prevention trials without obtaining parental permission. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 16.4 (2006) 379-396MuseSearchJournalsThis JournalContents[Access article in PDF]Pharmacists and Conscientious Objection *In March 2005, a Wisconsin pharmacist's act of conscience garnered headlines across the United States. After a married woman with four children submitted a prescription for the morning-after pill, the pharmacist, Neil Noesen, not only refused to fill it, but also refused to transfer the prescription to another pharmacist or to return the prescription (...) to the customer. As more such incidents occurred, many states "... decided to consider and enact laws setting the bounds of pharmacists' and other health care workers' professional obligations" (III, Grady 2006, p. 327). Discussions of objector legislation, also referred to as "conscience clauses," "refusal clauses," and "abandonment laws" (III, Appel 2005, p. 279), are not limited to professional ethics, but also draw from philosophical, theological, and legal perspectives. The purpose of this Scope Note is to present a wide variety of viewpoints on the health provider's right to conscience.More than 40 years ago the development of "The Pill" as the first reliable method of birth control not only ushered in a feminist revolution, but also provided a new focus for concerns of conscience for those who were part of the anti-abortion movement based on religious belief in the sanctity of life. Similarly, in the past ten years, worldwide, and seven years (1999) since the emergency contraception "morning after" pill first became available as a prescription item, there has been an upsurge in the number of medical personnel who refuse to prescribe or dispense it on grounds of personal conscience, whether for religious reasons or not. Their actions bring into play issues of power and control for health care personnel and for patients—in this case women, which also raises women's rights issues. Ironically, studies in France, Sweden, and the United Kingdom have shown that emergency contraception does not reduce the abortion rate—it is too infrequently used (II, Glasier 2006).It is important to underline the difference between the "morning-after" pill or "Plan B," which is made up of two progestin pills containing levonorgestrel (a synthetic derivative of the female hormone progesterone), and RU-486 (Mifiprex [End Page 379] or mifipristone with misoprostol). Plan B, if taken within 72 hours post-coitus prevents implantation, and therefore pregnancy, by suppressing the output of luteinizing hormone, the hormone that triggers the ovulation process. Scientists have been unable to determine whether this action could destroy already fertilized eggs, but even if it does, it uses the same mechanism as occurs with the birth-control pill, that was developed some 45 years ago. By contrast, RU-486 acts up to 49 days after implantation by blocking the action of progesterone in order to terminate the pregnancy and as such is an abortifacient (II, US FDA 1).On 24 August 2006, the U.S. Food and Drug Administration announced approval of the Plan B pill for over-the-counter (OTC ) sales (II, US FDA 2). Although this action makes the drug more widely available, it remains to be seen whether pharmacists who are conscientious objectors and who refuse to dispense it also will refuse to provide it OTC.A survey article by Rebecca Dresser (II, 2005, p. 9) succinctly sums up the problem for conscientious objectors: "Because emergency contraception can act to block implantation of a fertilized egg, people who believe in protection of human life after conception find it morally objectionable."When conscientious objections are raised over abortion or birth control services performed, prescribed, or dispensed, they affect not only the health professionals—physicians, pharmacists, nurses, and health technicians—who may object, as well as their colleagues and/or managers, but also the consumers: the female patients who are then forced to reconsider or to seek an alternative supplier, as well as their spouses or partners. Alta Charo (II, 2005, p. 2473) makes the point that the patient needs to have access to a system of counseling and referral "so... (shrink)