Ethical research when abortion access is legally restricted.

Risks and benefits of some clinical research may be altered.

Brief Report: Challenges in Obtaining the Informed Perspectives of Stakeholders Regarding HIV Molecular Epidemiology.

BACKGROUND: HIV molecular epidemiology (HIV-ME) is now being used in a variety of ways, including molecular HIV surveillance to help identify and respond to emerging HIV transmission clusters as specified in the Ending the HIV Epidemic in the U.S. initiative. However, HIV-ME in general, and its use for cluster detection and response, in particular, raises significant ethical and social concerns, which have spurred vigorous debates. Nevertheless, there is a paucity of information regarding how these potential benefits and concerns are perceived among people living with HIV and people without HIV at an increased risk. SETTING: Virtual engagement with US participants. METHODS: We rigorously developed a brief informational video about HIV-ME and conducted a series of in-depth interviews with people living with HIV and people without HIV at an increased risk. RESULTS: Through extensive stakeholder engagement during the video development process and subsequent in-depth interviews (N = 24), several preliminary findings surfaced. In contrast to the high level of concern raised by some critics of HIV-ME, our data appear to show broad support for it. In addition, we observed conflation of perspectives about HIV-ME with concerns about HIV public health surveillance more generally. CONCLUSION: Our experiences reveal substantial communication challenges related to the nature of HIV-ME that need to be overcome to ensure that it is properly understood, which is necessary for meaningfully engaging stakeholders in discussions about its use. Moreover, ongoing, responsive, engagement efforts are critical. Additional systematic data are needed to help inform policy making and practice regarding HIV-ME.

Scientific, ethical, and legal considerations for the inclusion of pregnant people in clinical trials.

Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration-approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.

The Pathway Forward: Insights on Factors that Facilitate Research with Pregnant Women.

The near-routine exclusion of pregnant women from clinical research has resulted in evidence gaps that endanger the health of pregnant women and their future offspring. Although existing literature documents numerous obstacles along the clinical trial pathway that can stymie research involving pregnant women, there is little guidance on how to facilitate such research. This qualitative study aims to fill that void by examining the experiences of individuals involved in conducting, approving, or overseeing research involving pregnant women at one academic institution. The study identifies factors throughout the clinical pathway-from protocol development, to IRB review, and ultimately trial execution-that likely contribute to the successful conduct of research with pregnant women. Attention to those factors, coupled with agreement among stakeholders that research with pregnant women should and can be done ethically and legally, is critical to shifting the narrative from "why we cannot" do such research to "how we can."

Ethical Considerations Concerning Amnioinfusions for Treating Fetal Bilateral Renal Agenesis.

Congenital bilateral renal agenesis has been considered a uniformly fatal condition. However, the report of using serial amnioinfusions followed by the live birth in 2012 and ongoing survival of a child with bilateral renal agenesis has generated hope, but also considerable controversy over an array of complex clinical and ethical concerns. To assess the ethical concerns associated with using serial amnioinfusions for bilateral renal agenesis, we assembled a multidisciplinary group to map the ethical issues relevant to this novel intervention. The key ethical issues identified were related to 1) potential risks and benefits, 2) clinical care compared with innovation compared with research, 3) counseling of expectant parents, 4) consent, 5) outcome measures, 6) access and justice, 7) conflicts of interest, 8) effects on clinicians, 9) effects on institutions, and 10) long-term societal implications. These ethical issues should be addressed in conjunction with systematic efforts to examine whether this intervention is safe and effective. Future work should capture the experiences of expectant parents, women who undergo serial amnioinfusions, those born with bilateral renal agenesis and their families as well as clinicians confronted with making difficult choices related to it.

Research with Pregnant Women: New Insights on Legal Decision-Making.

U.S. researchers and scholars often point to two legal factors as significant obstacles to the inclusion of pregnant women in clinical research: the Department of Health and Human Services' regulatory limitations specific to pregnant women's research participation and the fear of liability for potential harm to children born following a pregnant woman's research participation. This article offers a more nuanced view of the potential legal complexities that can impede research with pregnant women than has previously been reflected in the literature. It reveals new insights into the role of legal professionals throughout the research pathway, from product conception to market, and it highlights a variety of legal factors influencing decision-making that may slow or halt research involving pregnant women. Our conclusion is that closing the evidence gap created by the underrepresentation and exclusion of pregnant women in research will require targeted attention to the role of legal professionals and the legal factors that influence their decisions.

Ethics, regulation, and beyond: the landscape of research with pregnant women.

Scarce research with pregnant women has led to a dearth of evidence to guide medical decisions about safe and effective treatment and preventive interventions for pregnant women and their potential offspring. In this paper, we highlight three aspects of the landscape in which pregnant women are included or, more frequently, excluded from research: international ethics guidance, regional and national regulatory frameworks, and prevailing practices. Our paper suggests that, in some cases, regulatory frameworks can be more restrictive than international ethics guidance, and that even when regulations permit research with pregnant women, practical challenges-as well as the prevailing practices of stakeholders, such as ethics review committees and investigators-may lead to the generalized exclusion of pregnant women from research.

Just compensation: a no-fault proposal for research-related injuries.

Biomedical research, no matter how well designed and ethically conducted, carries uncertainties and exposes participants to risk of injury. Research injuries can range from the relatively minor to those that result in hospitalization, permanent disability, or even death. Participants might also suffer a range of economic harms related to their injuries. Unlike the vast majority of developed countries, which have implemented no-fault compensation systems, the United States continues to rely on the tort system to compensate injured research participants-an approach that is no longer morally defensible. Despite decades of US advisory panels advocating for no-fault compensation, little progress has been made. Accordingly, this article proposes a novel and necessary no-fault compensation system, grounded in the ethical notion of compensatory justice. This first-of-its-kind concrete proposal aims to treat like cases alike, offer fair compensation, and disburse compensation with maximum efficiency and minimum administrative cost. It also harmonizes national and international approaches-an increasingly important goal as research becomes more globalized, multi-site trials grow in number, and institutions and sponsors in the United States move to single-IRB review.

Respect and dignity: a conceptual model for patients in the intensive care unit.

Although the concept of dignity is commonly invoked in clinical care, there is not widespread agreement--in either the academic literature or in everyday clinical conversations--about what dignity means. Without a framework for understanding dignity, it is difficult to determine what threatens patients' dignity and, conversely, how to honor commitments to protect and promote it. This article aims to change that by offering the first conceptual model of dignity for patients in the intensive care unit. The conceptual model we present is based on the notion that there are three sources of patients' dignity-their shared humanity, personal narratives, and autonomy-each of which independently warrants respect. The article describes each source of dignity and draws on examples to illustrate how clinician attitudes, actions, and behaviors can either contribute to, or detract from, expressions of respect for patient dignity.

Moral gridlock: conceptual barriers to no-fault compensation for injured research subjects.

The federal regulations that govern biomedical research, most notably those enshrined in the Common Rule, express a protectionist ethos aimed at safeguarding subjects of human experimentation from the potential harms of research participation. In at least one critical way, however, the regulations have always fallen short of this promise: if a subject suffers a research-related injury, then neither the investigator nor the sponsor has any legal obligation under the regulations to care for or compensate the subject. Because very few subjects with research-related injuries can meet the financial or evidentiary requirements associated with a successful legal claim to recover the costs associated with their injuries, most injured subjects must shoulder the burden of those expenses alone. For 40 years, national advisory panels have concluded that this result is out of step with the Common Rule's otherwise protectionist promise. When the Department of Health and Human Services released an Advance Notice of Proposed Rulemaking (ANPRM) in 2011, suggesting potential changes to the Common Rule, the time seemed ripe to address research-related injuries. The ANPRM, however, makes no mention of compensation for research-related injuries, and the federal government once again seems poised to stop short of addressing what has arguably become the most longstanding, frequent, and consistent plea for regulatory reform of research: protections for injured subjects. This article asks why, despite decades of federal-level panels recommending no-fault compensation for research-related injuries, the United States has so strongly resisted change. I suggest that a central reason for our current impasse is that, despite consensus among federal advisory committees that there is an obligation to compensate injured subjects, the committees have not coalesced around a moral justification for that duty. Although multiple justifications can support and even strengthen a single ethical obligation, the reverse has occurred in this context. I demonstrate that the committees' articulation of multiple ethical principles - including humanitarianism, professional beneficence, and compensatory justice - results in incongruent obligations that favor different kinds of compensation systems. This outcome, which I call "moral gridlock," makes it extremely difficult to determine what kind of compensation scheme to implement. Recognizing that each moral argument for compensation creates a slightly different trajectory is, however, an important first step in moving toward a more systematic approach to compensating injured research subjects.