Whether life insurers should be able to consider genetic information during underwriting is a long-standing debate often characterized by strong opinions on both sides. Insurers push for full access to applicants' genetic information, and consumer advocates often call for a ban on insurer use of the information. Both sides employ concepts of fairness and discrimination in supporting their position. This article considers the concept of actuarial fairness, where individuals are expected to pay for the risks they bring to an insurance pool. Currently, law and policy adopting this standard most often take a deferential approach, allowing insurers to utilize genetic information with wide latitude. This article takes seriously a middle-ground approach, broadly labeled as actuarial utility. Building from prior literature examining this issue, this article proposes a framework US policy can adopt to assist in the assessment of the actuarial utility of genetic information with a particular focus on emerging genetic technologies.

Clinical research in persons with a terminal illness (PTI) can offer valuable scientific opportunities but raises the challenge of ensuring adequate protections for participants. Existing ethical frameworks provide limited, and sometimes conflicting guidance for navigating this tension. Given that enrolling only PTI (e.g., palliative care research) or PTI alongside participants without a terminal illness (many studies in geriatrics and other disciplines) is somewhat common, establishing the right balance is important. This paper-grounded in general research ethics requirements-thus proposes a framework based on the defining feature of PTI, namely, limited life expectancy. We explore how limited life expectancy and characteristics common (but not unique to) PTI (e.g., decisional impairment) can make it difficult for studies to meet one or more commonly recognized ethical requirements (e.g., social value, favorable risk-benefit ratio, fair participant selection, informed consent, and respect for participants and third parties). We suggest ways to address these challenges and offer considerations for IRBs when evaluating studies with adults with a terminal illness. This approach aims to balance protecting PTI and ensuring they can contribute to important research without undue restrictions.

Previous studies suggest that NIPT's implementation differed widely across countries but offer limited insight into what shaped these differences. To address this gap, we conducted an in-depth analysis of how NIPT was incorporated into prenatal care in the US, the Netherlands, and Japan-countries with similar economic status-to identify actionable lessons. We conducted an integrative literature review on the process of introducing and implementing NIPT, stakeholders' roles, documented considerations in the decision to introduce NIPT, implementation choices, and NIPT uptake. We included 184 sources, including white and gray literature and non-English sources. We identified 17 considerations that were documented to have influenced the decision whether to introduce NIPT across five domains: clinical considerations, ethical considerations and societal values, financial considerations, demand and capacity and applicable oversight. Fewer factors seem to have been considered in the US as compared to Japan or the Netherlands. Countries subsequently made choices on how to implement NIPT-we identified 35 such choices. While most of the identified choices were eventually considered by all three countries, they made different decisions (e.g., on out-of-pocket costs). In 2022, the estimated proportion of pregnant persons who used NIPT was 58% in the Netherlands, 49% in the US, and 9% in Japan. While differences in cultural values, population characteristics, and healthcare systems explain some variation, we identified other more adaptable aspects of the decision-making process (e.g., oversight) that may be useful for countries introducing NIPT or similar technologies to consider.

The majority of genomic sequencing and microarray results are clinically uninformative, meaning that they do not suggest a need for any behavioral action or medical intervention. Prior studies have shown that recipients of uninformative genomic testing results ("uninformative results" hereafter) may incorrectly interpret them to imply a lowered risk of disease or false reassurance about future health risks. Few studies have examined how patients understand uninformative results when they are returned in a research setting, where there is wide variation in analytical specifications of testing, interpretation and reporting practices, and resources to support the return of results. We conducted cross-sectional interviews (N = 17) to explore how a subset of research participants in one genomics study at the National Institutes of Health reacted to and understood their uninformative test results, which were returned to them via a patient portal without genetic counseling. We found that most participants did not remember the details of the informed consent process, including the distinction between "primary" and "secondary" findings. Participants had questions about what genes were tested for and, in most cases, requested a list of the genes covered. Several participants incorrectly assumed that autosomal recessive carrier results would have been reported to them if detected. Some participants interpreted their uninformative results to mean that they could forgo prenatal testing, and participants had mixed expectations about whether their results might be reinterpreted in the future. These themes suggest that there are specific challenges to returning uninformative results in research settings. Educational supplements to uninformative test reports may be most useful if they contextualize results in relation to other types of clinical genetic or genomic testing that may be made available to research participants in their lifetimes.

BACKGROUND:Though genomic science has rapidly advanced, efforts to demonstrate the population-level utility of genomics have been slow to follow. It has long been argued that the family is an important unit of significance in genomics, yet it has been challenging to address this in clinical care. This is apparent in how hospital administrators and clinicians in the United States typically approach cascade screening, the process of notifying and offering genetic testing to at-risk relatives of a patient with a hereditary condition. The most common notification approach is proband-led contact, in which the index patient is responsible for communicating a health risk to their relatives. This model has been associated with suboptimal outcomes. In contrast, recent research has shown that system-led contact, in which healthcare or public health institutions initiate communication to relatives with the proband's consent, has been associated with increased clinical utility and acceptability. SUMMARY:With the needs of hospital administrators and clinicians in mind, we revisit normative questions about the appropriate way to notify relatives about their potentially elevated risk of developing an actionable disease. We review evidence demonstrating that system-led direct contact of relatives is feasible and acceptable. We further argue that system-led contact of relatives eligible for cascade screening is ethically justified if these programs are designed with public input, have an opt-out provision, and are implemented for conditions that meet specific criteria which we propose in this article. KEY MESSAGES:In this article, we emphasize the usefulness of public health ethics frameworks to inform the design of system-led contact programs. Beyond this, we make the case that such programs are necessary to realize the population utility of genomic medicine equitably.

(Abstracted from Genet Med 26:101052) Polygenic risk scores (PRSs) quantify the combined associations of multiple single nucleotide variations in an individual’s genome to estimate their likelihood of developing certain diseases based on population data. Although PRS availability for adults is currently limited, it is expected to grow.

Purpose: To assess intended parents’ preferences about expanded prenatal cell-free DNA screening. Methods: A survey was administered to couples who were pregnant or trying to conceive. Partners within couples were independently asked about willingness to seek prenatal cell-free DNA screening for diseases and traits that varied by severity, treatability, age of onset, and reliability. Additional questions explored couples’ decision-making processes and how various factors would affect those decisions. Results: Respondents (n = 494) were most likely to seek a prenatal genetic test when the test is completely predictive (P value of predictability effect = .0116), for earlier onset (P value of onset effect = .0310), treatable diseases (P value of treatability effect = .0032), and of highest severity (P value of severity effect < .0001). Living in states where termination was not available was not associated with decreased interest in prenatal screening, with 45% reporting that it would make them more likely to seek testing. There was moderate concordance between couples about their testing decisions and the majority of pregnant persons (68.8%) and partners (66.7%) desired firm screening recommendations from their doctors. Conclusion: These data suggest that couples are highly information seeking when presented with all testing options neutrally, but most desire to be presented with firm testing recommendations from their clinician.

The article argues the thesis that institutions have a prima facie obligation to fund the feedback of individual findings in genomic research conducted on the African continent by drawing arguments from an underexplored Afro-communitarian view of distributive justice and rights of researchers to be aided. Whilst some studies have explored how institutions have a duty to support return as a form of ancillary care or additional foreseeable service in research by mostly appealing to dominant principles and theories in the Global North, this mostly normative study explores this question by appealing to underexplored African philosophy. This is a new way of thinking about institutional responsibility to fund feedback and responds to the call to decolonise health research in Africa. Further studies are required to study how this prima facie obligation will interact with social contexts and an institution’s extant relationships to find an actual duty. The research community should also work out procedures, policies and governance structures to facilitate feedback. In our opinion, though the impacts of feeding back can inform how institutions think about their actual duty, these do not obliterate the binding duty to fund feedback.

BACKGROUND:Genetic research can yield information that is unrelated to the study's objectives but may be of clinical or personal interest to study participants. There is an emerging but controversial responsibility to return some genetic research results, however there is little evidence available about the views of genomic researchers and others on the African continent. METHODS:We conducted a continental survey to solicit perspectives of researchers, science policy makers and research ethics committee members on the feedback of individual genetic research findings in African genomics research. RESULTS:A total of 110 persons participated in the survey with 51 complete and 59 incomplete surveys received. Data was summarised using descriptive analysis. Overall, our respondents believed that individual genetic research results that are clinically actionable should be returned to study participants apparently because participants have a right to know things about their health, and it might also be a means for research participation to be recognized. Nonetheless, there is a need for development of precise guidance on how to return individual genetic research findings in African genomics research. DISCUSSION:Participants should receive information that could promote a healthier lifestyle; only clinically actionable findings should be returned, and participants should receive all important information that is directly relevant to their health. Nevertheless, detailed guidelines should inform what ought to be returned. H3Africa guidelines stipulate that it is generally considered good practice for researchers to feedback general study results, but there is no consensus about whether individual genomic study results should also be fed back. The decision on what individual results to feedback, if any, is very challenging and the specific context is important to make an appropriate determination.

Click to increase image sizeClick to decrease image sizeThis article refers to:Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on DisabilityThis article is referred to by:Permit Assisted Self-Administration: A Response to Open Peer Commentaries on Neurologic Diseases and Medical Aid in Dying: Aid-in-Dying Laws Create an Underclass of Patients Based on Disability ACKNOWLEDGEMENTSThe views expressed here are our own and do not represent the views or policies of the Department of Health and Human Services or the National Institutes of Health.Notes1 California End of Life Option Act, Cal. Health & Safety Code §§ 443.1-.22; Colorado End of Life Options Act, Colo. Rev. Stat §§ 25-48-101 to -123; Hawaii Our Care, Our Choice Act, Haw. Rev. Stat. §§327L-1 to -25; New Jersey Aid in Dying for the Terminally Ill Act, N.J. Stat. §§ 26:16-1 to -20.2 Americans with Disabilities Act, 1990. 42 U.S.C. §§ 12132.3 29 CFR Ch. XIV, § 1630.16.4 Lonny Shavelson, M.D., et al., Plaintiffs, v. Robert Bonta, et al., Defendants. 21-cv-06654-VC (United States District Court, Northern District of California, 2022).Additional informationFundingThis research was funded by the Intramural Research Program at the National Institutes of Health Clinical Center, and by the National Human Genome Research Institute Bioethics Core (Grant number 1ZIDHG200347).

ObjectiveRisks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies.MethodWe used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies.ResultsClinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place.ConclusionConsidering these points may advance the interests of fetuses, future children, and their families. What's already known about this topic?After an initial clinical study, the risks and benefits of an experimental fetal therapy can remain uncertain.While further research is still needed to justify the integration of such therapies into standard of care, clinicians may be asked to provide them outside research.What does this study add?We propose points for consideration when deciding whether and how to offer experimental fetal therapies outside research following initial clinical studies.

Click to increase image sizeClick to decrease image sizeThis article refers to:Non-Invasive Prenatal Testing for “Non-Medical” Traits: Ensuring Consistency in Ethical Decision-Making DISCLOSURE STATEMENTThe views herein are those of the authors and do not represent the views or policies of the Department of Health and Human Services or the National Institutes of Health.Additional informationFundingThis research was supported in part by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health.

The failure of many patients with chronic conditions to correctly follow medical advice that they hope or intend to follow is a major concern, especially as effective long-term therapies for chronic conditions materialize. Some US healthcare providers have responded with strategies that involve implementing contracts with their patients, including provisions that may deny future treatments after continued nonadherence. This is among the first articles to explicitly discuss the ethics of patient contracts.

Background: During the COVID-19 pandemic, frontline workers faced a series of challenges balancing family and work responsibilities. These challenges included making decisions about how to reduce COVID-19 exposure to their families while still carrying out their employment duties and caring for their children. We sought to understand how frontline workers made these decisions and how these decisions impacted their experiences.Methods: Between October 2020 and May 2021, we conducted 61 semi-structured interviews in English or Spanish, with individuals who continued to work outside of the home during the pandemic and had children living at home. Interviews were recorded, transcribed verbatim, and analyzed using abductive methods.Results: Frontline workers experienced moral distress, the inability to act in accordance with their values and obligations because of internal or external constraints. Their moral distress was a result of the tensions they felt as workers and parents, which sometimes led them to feel like they had to compromise on either or both responsibilities. Individuals felt morally conflicted because 1) their COVID-19 work exposures presented risk that often jeopardized their family's health; 2) their work hours often conflicted with their increased childcare responsibilities; and 3) they felt a duty to their colleagues, patients/customers, and communities to continue to show-up to work.Conclusions: Our findings point to a need to expand the concept of moral distress to include the perspectives of frontline workers outside of the healthcare professions and the fraught decisions that workers make outside of work that may impact their moral distress. Expanding the concept of moral distress also allows for a justice-based framing that can focus attention on the disparities inherent in much frontline work and can justify programmatic recommendations, like increasing paid childcare opportunities, to alleviate moral distress.

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk-benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research (e.g., only for life-threatening conditions). Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study's social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk-benefit ratios for pregnant women and/or fetuses may be acceptable.

In this article, we examine the legality and ethics of a controversial but widespread practice in clinical research: choice-masking nudges. A choice-masking nudge (CMN) exists when a research team explicitly obscures a meaningful choice from participants by presenting a default decision as the standard way forward. Even though an easy-to-use opt-out mechanism is available for participants who independently express concerns with the standard default, the fact that a default has been pre-selected is not made obvious to research participants. To opt out of the nudge, a participant must overtly request non-standard treatment. We argue that use of such nudges in medical research can be justified by their individual, collective, and social benefits, provided that they respect autonomy and satisfy our four further acceptability conditions. The structure of this Article is as follows. In Part II, we describe three controversial cases of CMNs in medical research. In Part III, we provide background on nudging and explain how our proposed CMNs fit into the existing literature on nudging and libertarian paternalism. In Part IV, we explain how the reasonable person standard as employed by United States research regulations can be used to support CMNs. In Part IV, we anticipate some of the strongest objections to CMNs by explaining how CMNs are compatible with a wide range of plausible accounts of autonomy. Finally, in Part VI, we discuss four additional core considerations an acceptable CMN must meet: legitimate policy goals; benefits outweighing harms; burdens distributed fairly; and absence of ethically superior feasible alternatives. We also analyze the three existing controversies explored in Part II and show how each would benefit from the conceptual clarity offered by our analytic framework. Medical research is complicated and can be difficult for participants to understand; thoughtfully designed CMNs can play an important role in gently guiding large numbers of research participants toward decision outcomes that really are best for them and their communities.