Industry price guarantees for publicly funded medicines: learning from Project NextGen for pandemics and beyond.

The affordability of publicly funded medicines has been a longstanding concern. In 2023, the Biden administration took several steps on this front, including incorporation of a price constraint in an agreement between the US Biomedical Advanced Research and Development Authority (BARDA) and Regeneron Pharmaceuticals, Inc. to develop a new COVID-19 monoclonal antibody. The agreement included a 'Most Favored Nation' (MFN) clause in which Regeneron agreed that the US commercial list price of certain products developed using BARDA funding would not exceed their retail price in comparable global markets. The Administration for Strategic Preparedness and Response (ASPR) included similar language in subsequent agreements, with a promise that this would become a new standard. Even beyond the preparedness context, government funders and purchasers might consider incorporating similar clauses in future contracts, especially given that the Regeneron agreement and its progeny have been praised as 'groundbreaking.' Yet a closer look reveals cause for skepticism. Regeneron's MFN clause includes several loopholes related to covered purchasers and reference countries, prices, and conditions. We describe agreement terms that can make the difference between legally meaningful price constraints and mere window dressing. Our critical analysis offers important lessons for future efforts to improve the affordability of medical technology developed with public funds.

Who Will Save Legal Access to Emergency Abortion?

This Viewpoint discusses whether the federal EMTALA act requires that hospitals provide abortions when needed to protect the health of the pregnant person, even if prohibited by state law.

Checks and Balances on FDA's Authority.

In this Viewpoint, the authors refute recent suggestions that the US Food and Drug Administration (FDA) is not accountable for its decisions, pointing out the legal, legislative, and executive checks and balances on the agency.

Big Mistake: Knowing and Doing Better in Patient Engagement.

Pushing back on policies favored by dying patients is a challenging endeavor, requiring tact, engagement, openness to bidirectional learning, and willingness to offer alternative solutions. It's easy to make missteps, especially in the age of social media. Holly Fernandez Lynch shares her experience learning with and from the amyotrophic lateral sclerosis (ALS) community, first as a caricature of an ivory tower bioethicist and more recently as a trusted advisor, at least for some. Patient-engaged bioethics doesn't mean taking the view that patients are always right, but even when disagreement continues, progress is possible if academics and patients recognize the unique expertise each has to offer.

Ethically cleared to launch?

Rules are needed for human research in commercial spaceflight.

Inclusive, engaged, and accountable institutional review boards.

In February 2023, the U.S. Government Accountability Office (GAO) released another report acknowledging that we still lack meaningful, validated, widely-accepted measures for evaluating institutional review board (IRB) quality and effectiveness. This challenge is well known to the Consortium to Advance Effective Research Ethics Oversight (www.AEREO.org), a collaborative group of human research protection (HRP) professionals, researchers, and research ethicists founded in 2018 to do precisely what GAO recommends: examine approaches for measuring IRB effectiveness in protecting human subjects, and implement the approaches as appropriate. Two underlying tenets have been central to AEREO's as approach to thinking about IRB quality and effectiveness: (1) IRBs exist to protect participants and thus the participant perspective should be central to all IRBs do; and (2) because IRBs are tasked with applying subjective ethical and regulatory standards about which people may disagree, their approach and decisions should at least meet the basic standard of reasonableness in terms of accounting for relevant perspectives, considering key factors, and providing defensible justifications. Critical to each of these tenets, IRBs should include diverse perspectives in their deliberations, find ways to meaningfully engage with relevant communities about their views regarding ethical research and appropriate participant protections, and be accountable to the public.

Devil in the Details: Physician Duties and Expanded Access.

Vermeulen et al. suggest a moral duty exists for physicians to inform patients of "relevant opportunities" for Expanded Access. Such a duty is likely both too broad, leading to important practical challenges, and too narrow, without further steps to promote patient access. However, physicians should be expected to be aware of the EA pathway, disclose it to eligible patients, and support the pursuit of EA options reasonably likely to help.

Pressing regulatory challenges for psychedelic medicine.

Policy must support generation of evidence on safety and effectiveness.

Journeying to Ixtlan: Ethics of Psychedelic Medicine and Research for Alzheimer's Disease and Related Dementias.

In this paper, we examine the case of psychedelic medicine for Alzheimer's disease and related dementias (AD/ADRD). These "mind-altering" drugs are not currently offered as treatments to persons with AD/ADRD, though there is growing interest in their use to treat underlying causes and associated psychiatric symptoms. We present a research agenda for examining the ethics of psychedelic medicine and research involving persons living with AD/ADRD, and offer preliminary analyses of six ethical issues: the impact of psychedelics on autonomy and consent; the impact of "ego dissolution" on persons experiencing a pathology of self; how psychedelics might impact caregiving; the potential exploitation of patient desperation; institutional review boards' orientation to psychedelic research; and methods to mitigate inequity. These ethical issues are magnified for AD/ADRD but bear broader relevance to psychedelic medicine and research in other clinical populations.

Bioethics and the Moral Authority of Experience.

While experience often affords important knowledge and insight that is difficult to garner through observation or testimony alone, it also has the potential to generate conflicts of interest and unrepresentative perspectives. We call this tension the paradox of experience. In this paper, we first outline appeals to experience made in debates about access to unproven medical products and disability bioethics, as examples of how experience claims arise in bioethics and some of the challenges raised by these claims. We then motivate the idea that experience can be an asset by appealing to themes in feminist and moral epistemology, distinguishing between epistemic and justice-based appeals. Next, we explain the concern that experience may be a liability by appealing to empirical work on cognitive biases and theoretical work about the problem of partial representation. We conclude with preliminary recommendations for addressing the paradox and offer several questions for future discussion.

Diversity in IRB Membership: Views of IRB Chairpersons at U.S. Universities and Academic Medical Centers.

BACKGROUND: Diversity in Institutional Review Board (IRB) membership is important for both intrinsic and instrumental reasons, including fairness, promoting trust, improving decision quality, and responding to systemic racism. Yet U.S. IRBs remain racially and ethnically homogeneous, even as gender diversity has improved. Little is known about IRB chairpersons' perspectives on membership diversity and barriers to increasing it, as well as current institutional efforts to promote diversity, equity, and inclusion (DEI) within IRB membership. METHODS: We surveyed IRB chairpersons leading U.S. boards registered with the Office for Human Research Protections. Here, we focus exclusively on responses from a subset of 388 chairpersons of IRBs at universities and academic medical centers (AMCs). RESULTS: Board chairs were predominantly white and evenly split between men and women. Only about half reported that their boards had at least one member who is Black or African American (51%), Asian (56%), or Hispanic (48%), with 85% of university/AMC boards comprised entirely (15%) or mostly (70%) of white members. Most IRB chairpersons (64%) reported satisfaction with the current diversity of their membership. Participants largely agreed that considering diversity in the selection of IRB members is important (91%), including to improve the quality of IRB deliberation (80%), with an emphasis on racial/ethnic (85%) and gender diversity (74%). Most participants (80%) reported some type of active DEI effort regarding board membership at their university/AMC and just over half (57%) expressed satisfaction with these efforts. CONCLUSIONS: Our national survey found that although university/AMC IRB chairpersons report valuing diversity in board membership, it may be lacking in key areas. Going forward, it will be important to specify clear reasons for diversity in the IRB context, as well to establish targets for acceptable levels of board diversity and to match DEI efforts to those targets.

Institutional Review Board Use of Outside Experts: A National Survey.

BACKGROUND: Institutional review board (IRB) expertise is necessarily limited by maintaining a manageable board size. IRBs are therefore permitted by regulation to rely on outside experts for review. However, little is known about whether, when, why, and how IRBs use outside experts. METHODS: We conducted a national survey of U.S. IRBs to characterize utilization of outside experts. Our study uses a descriptive, cross-sectional design to understand how IRBs engage with such experts and to identify areas where outside expertise is most frequently requested. RESULTS: The survey response rate was 18.4%, with 55.4% of respondents reporting their institution's IRB uses outside experts. Nearly all respondents who reported using outside experts indicated they do so less than once a month, but occasionally each year (95%). The most common method of identifying an outside expert was securing a previously known subject matter expert (83.3%). Most frequently, respondents sought consultation for scientific expertise not held by current members (69.6%). Almost all respondents whose IRBs had used outside experts reported an overall positive impact on the IRB review process (91.5%). CONCLUSIONS: Just over half of the IRBs in our sample report use of outside experts; among them, outside experts were described as helpful, but their use was infrequent overall. Many IRBs report not relying on outside experts at all. This raises important questions about what type of engagement with outside experts should be viewed as optimal to promote the highest quality review. For example, few respondents sought assistance from a Community Advisory Board, which could address expertise gaps in community perspectives. Further exploration is needed to understand how to optimize IRB use of outside experts, including how to recognize when expertise is lacking, what barriers IRBs face in using outside experts, and perspectives on how outside expert review impacts IRB decision-making and review quality.

Aspiring to Reasonableness in Accelerated Approval: Anticipating and Avoiding the Next Aducanumab.

The US Food and Drug Administration's decisions about drug approval-though guided by science, as well as relevant statutes, regulations, and guidance documents-reflect normative judgments about how the agency should exercise its discretion. This is particularly true in the context of the "accelerated approval" pathway, where the agency must balance speeding to market drugs for patients with unmet needs before they have been proven to work and ensuring confidence about the benefits and risks of those drugs. A key challenge in evaluating normative judgments such as these is that reasonable people can disagree, rendering it difficult to proclaim with certainty that a particular decision is right or wrong. Therefore, we propose that it is preferable to ask whether a decision is reasonable. A decision is reasonable when it transparently, comprehensively, and fairly balances the interests of affected parties, within the parameters of the decision maker's legal authority. If a decision achieves these three qualities, it can be viewed as legitimate and worthy of trust and confidence, regardless of whether one agrees with the particular outcome. We recommend that the Food and Drug Administration adopt procedural protections to promote reasonableness in four domains affecting accelerated approval decisions: pathway gatekeeping, endpoint selection, stakeholder engagement, and deliberation. This should aid the agency in minimizing controversies, such as that surrounding the 2021 approval of aducanumab (Aduhelm; Biogen).

INTRODUCTION Health Law and Anti-Racism: Reckoning and Response.

Law and racism are intertwined, with legal tools bearing the potential to serve as instruments of oppression or equity. This Special Issue explores this dual nature of health law, with attention to policing in the context of mental health, schools, and substance use disorders; industry and the environment in the context of food advertising, tobacco regulation, worker safety, and environmental racism; health care and research in the context of infant mortality, bias in medical applications of AI, and diverse inclusion in research; and anti-racist teaching and practice in the context of building an interprofessional curriculum and medical-legal partnerships.

Off-Label Prescription of COVID-19 Vaccines in Children: Clinical, Ethical, and Legal Issues.

The US Food and Drug Administration (FDA) approval of the biologics license application for the Pfizer-BioNTech coronavirus disease 2019 vaccine (Comirnaty) on August 23, 2021, opened the door to the off-label vaccination of children younger than the age range currently covered by either the biologics license application (16 years old and older) or the emergency use authorization (12 to 15 years old). Although prescribing medications at doses, for conditions, or in populations other than those approved by the FDA is generally legal and is common in pediatrics, the FDA, the Centers for Disease Control and Prevention, and the American Academy of Pediatrics have recommended against off-label prescription of the coronavirus disease 2019 vaccine. Several commentaries consider a case in which parents ask their child's pediatrician to prescribe the vaccine for their 11-year-old with special health care needs before approval or authorization in her age group. The first commentary considers the potential benefits and risks to the patient, as well as to the family, the provider, and society, emphasizing the unknown risks in younger patients and the need for adequate informed consent. The second commentary describes an algorithm and principles for evaluating off-label prescribing and argues that the current benefits of prescribing Comirnaty off label to children <12 do not outweigh the risks. The third commentary addresses ethical and legal issues, ultimately calling on federal agencies to remove legal barriers to making the vaccine available to children in age groups that currently lack authorization.