Trends in U.S. public confidence in science and opportunities for progress.

In recent years, many questions have been raised about whether public confidence in science is changing. To clarify recent trends in the public's confidence and factors that are associated with these feelings, an effort initiated by the National Academies' Strategic Council for Research Excellence, Integrity, and Trust (the Strategic Council) analyzed findings from multiple survey research organizations. The Strategic Council's effort, which began in 2022, found that U.S. public confidence in science, the scientific community, and leaders of scientific communities is high relative to other civic, cultural, and governmental institutions for which researchers regularly collect such data. However, confidence in these institutions has fallen during the previous 5 years. Science's decline, while real, is similar to or less than that in the other groups. A recent study goes into greater detail by exploring public views of science. From these data, we observe that many of the surveyed U.S. public question the extent to which scientists share their values or overcome personal biases when presenting conclusions. At the same time, large majorities agree on certain types of actions that they want scientists to take. For example, 84% respond that it is "somewhat important" or "very important" for scientists to disclose their funders. Ninety-two percent (92%) offer the same responses to scientists "being open to changing their minds based on new evidence." Collectively, these data clarify how the U.S. public views science and scientists. They also suggest actions that can affect public confidence in science and scientists in the years to come.

Return of Results in Genomic Research Using Large-Scale or Whole Genome Sequencing: Toward a New Normal.

Genome sequencing is increasingly used in research and integrated into clinical care. In the research domain, large-scale analyses, including whole genome sequencing with variant interpretation and curation, virtually guarantee identification of variants that are pathogenic or likely pathogenic and actionable. Multiple guidelines recommend that findings associated with actionable conditions be offered to research participants in order to demonstrate respect for autonomy, reciprocity, and participant interests in health and privacy. Some recommendations go further and support offering a wider range of findings, including those that are not immediately actionable. In addition, entities covered by the US Health Insurance Portability and Accountability Act (HIPAA) may be required to provide a participant's raw genomic data on request. Despite these widely endorsed guidelines and requirements, the implementation of return of genomic results and data by researchers remains uneven. This article analyzes the ethical and legal foundations for researcher duties to offer adult participants their interpreted results and raw data as the new normal in genomic research.

Assessment of stored red blood cells through lab-on-a-chip technologies for precision transfusion medicine.

Transfusion of red blood cells (RBCs) is one of the most valuable and widespread treatments in modern medicine. Lifesaving RBC transfusions are facilitated by the cold storage of RBC units in blood banks worldwide. Currently, RBC storage and subsequent transfusion practices are performed using simplistic workflows. More specifically, most blood banks follow the "first-in-first-out" principle to avoid wastage, whereas most healthcare providers prefer the "last-in-first-out" approach simply favoring chronologically younger RBCs. Neither approach addresses recent advances through -omics showing that stored RBC quality is highly variable depending on donor-, time-, and processing-specific factors. Thus, it is time to rethink our workflows in transfusion medicine taking advantage of novel technologies to perform RBC quality assessment. We imagine a future where lab-on-a-chip technologies utilize novel predictive markers of RBC quality identified by -omics and machine learning to usher in a new era of safer and precise transfusion medicine.

Governing new technologies that stop biological time: Preparing for prolonged biopreservation of human organs in transplantation.

Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients. However, the safety and efficacy of advanced biopreservation with prolonged storage of vascularized organs followed by reanimation will require new regulatory oversight, as clinicians and transplant centers are not trained in the engineering techniques involved or equipped to assess the manipulated organs. Although the Food and Drug Administration is best situated to provide that process oversight, the agency has until now declined to oversee organ quality and has excluded vascularized organs from the oversight framework of human cells, tissues, and cellular-based and tissue-based products. Integration of advanced biopreservation technologies will require new facilities for organ preservation, storage, and reanimation plus ethical guidance on immediate organ use versus preservation, national allocation, and governance of centralized organ banks. Realization of the long-term benefit of advanced biopreservation requires anticipation of the necessary legal and ethical oversight tools and that process should begin now.

Scientists' perspectives on ethical issues in research with emerging portable neuroimaging technology: The need for guidance on ethical, legal, and societal implications (ELSI).

Deployment of new, more portable, and less costly neuroimaging technologies such as portable magnetoencephalography, electroencephalography, positron emission tomography, functional near-infrared spectroscopy, high-density diffuse optical tomography, and magnetic resonance imaging is advancing rapidly. Given this trajectory toward increasing use of neuroimaging outside the hospital, we sought to identify ethical, legal, and societal implications (ELSI) of these new technologies by understanding the perspectives of those scientists and engineers developing and implementing portable neuroimaging technologies in the United States, Europe, and Asia. Based on a literature review, we identified and contacted 19 potential interviewees and then conducted 11 semi-structured interviews in English by Zoom. Analysis of the interviews revealed key themes and ELSI issues. Developers reported that without proper ELSI guidance, portable and accessible neuroimaging technology could be misused, fail to comply with applicable regulation and policy, and ultimately fall short in its mission to provide neuroimaging for the world. Our interviews suggested that ELSI guidance should address differences between imaging modalities because they vary in capability, limitations, and likelihood of generating incidental findings.

Safeguarding Earth's biodiversity by creating a lunar biorepository.

Earth's biodiversity is increasingly threatened and at risk. We propose a passive lunar biorepository for long-term storage of prioritized taxa of live cryopreserved samples to safeguard Earth's biodiversity and to support future space exploration and planet terraforming. Our initial focus will be on cryopreserving animal skin samples with fibroblast cells. An exemplar system has been developed using cryopreserved fish fins from the Starry Goby, Asterropteryx semipunctata. Samples will be expanded into fibroblast cells, recryopreserved, and then tested in an Earth-based laboratory for robust packaging and sensitivity to radiation. Two key factors for this biorepository are the needs to reduce damage from radiation and to maintain the samples near -196° Celsius. Certain lunar sites near the poles may meet these criteria. If possible, further testing would occur on the International Space Station prior to storage on the Moon. To secure a positive shared future, this is an open call to participate in this decades-long program.

Emerging ethical issues raised by highly portable MRI research in remote and resource-limited international settings.

Smaller, more affordable, and more portable MRI brain scanners offer exciting opportunities to address unmet research needs and long-standing health inequities in remote and resource-limited international settings. Field-based neuroimaging research in low- and middle-income countries (LMICs) can improve local capacity to conduct both structural and functional neuroscience studies, expand knowledge of brain injury and neuropsychiatric and neurodevelopmental disorders, and ultimately improve the timeliness and quality of clinical diagnosis and treatment around the globe. Facilitating MRI research in remote settings can also diversify reference databases in neuroscience, improve understanding of brain development and degeneration across the lifespan in diverse populations, and help to create reliable measurements of infant and child development. These deeper understandings can lead to new strategies for collaborating with communities to mitigate and hopefully overcome challenges that negatively impact brain development and quality of life. Despite the potential importance of research using highly portable MRI in remote and resource-limited settings, there is little analysis of the attendant ethical, legal, and social issues (ELSI). To begin addressing this gap, this paper presents findings from the first phase of an envisioned multi-staged and iterative approach for creating ethical and legal guidance in a complex global landscape. Section 1 provides a brief introduction to the emerging technology for field-based MRI research. Section 2 presents our methodology for generating plausible use cases for MRI research in remote and resource-limited settings and identifying associated ELSI issues. Section 3 analyzes core ELSI issues in designing and conducting field-based MRI research in remote, resource-limited settings and offers recommendations. We argue that a guiding principle for field-based MRI research in these contexts should be including local communities and research participants throughout the research process in order to create sustained local value. Section 4 presents a recommended path for the next phase of work that could further adapt these use cases, address ethical and legal issues, and co-develop guidance in partnership with local communities.

Ethical Challenges Arising in the COVID-19 Pandemic: An Overview from the Association of Bioethics Program Directors (ABPD) Task Force.

The COVID-19 pandemic has raised a host of ethical challenges, but key among these has been the possibility that health care systems might need to ration scarce critical care resources. Rationing policies for pandemics differ by institution, health system, and applicable law. Most seem to agree that a patient's ability to benefit from treatment and to survive are first-order considerations. However, there is debate about what clinical measures should be used to make that determination and about other factors that might be ethically appropriate to consider. In this paper, we discuss resource allocation and several related ethical challenges to the healthcare system and society, including how to define benefit, how to handle informed consent, the special needs of pediatric patients, how to engage communities in these difficult decisions, and how to mitigate concerns of discrimination and the effects of structural inequities.

Improving recommendations for genomic medicine: building an evolutionary process from clinical practice advisory documents to guidelines.

Genomic sequencing and multigene panel tests are moving rapidly into clinical practice for a range of indications, but the evidence to guide appropriate use is currently limited. Well-crafted advice is needed to reduce unjustified practice variation, minimize risk of error and harm to patients, and encourage best practices. In the absence of definitive evidence, provisional advice can be helpful if it clarifies the potential benefits and risks of different courses of action and identifies the knowledge gaps most important to address in future research. This paper proposes an evolutionary process starting with clinical practice advisory documents (CPADs) and culminating in clinical practice guidelines (CPGs), using two case examples to illustrate the need for this process. When evidence is limited, CPADs can clarify current practice options and identify key knowledge gaps. Added evidence can then support updates to the CPADs over time. Ultimately CPADs can provide the foundation for definitive CPGs as the evidence base matures. This approach addresses an important challenge in genomics and may be applicable to other fields in which technology and practice are outpacing evidence generation.

Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium.

PurposeThe Clinical Sequencing Exploratory Research (CSER) Consortium encompasses nine National Institutes of Health-funded U-award projects investigating translation of genomic sequencing into clinical care. Previous literature has distinguished norms and rules governing research versus clinical care. This is the first study to explore how genomics investigators describe and navigate the research-clinical interface.MethodsA CSER working group developed a 22-item survey. All nine U-award projects participated. Descriptive data were tabulated and qualitative analysis of text responses identified themes and characterizations of the research-clinical interface.ResultsSurvey responses described how studies approached the research-clinical interface, including in consent practices, recording results, and using a research versus clinical laboratory. Responses revealed four characterizations of the interface: clear separation between research and clinical care, interdigitation of the two with steps to maintain separation, a dynamic interface, and merging of the two. All survey respondents utilized at least two different characterizations. Although research has traditionally been differentiated from clinical care, respondents pointed to factors blurring the distinction and strategies to differentiate the domains.ConclusionThese results illustrate the difficulty in applying the traditional bifurcation of research versus clinical care to translational models of clinical research, including in genomics. Our results suggest new directions for ethics and oversight.

Return of genomic results to research participants: the floor, the ceiling, and the choices in between.

As more research studies incorporate next-generation sequencing (including whole-genome or whole-exome sequencing), investigators and institutional review boards face difficult questions regarding which genomic results to return to research participants and how. An American College of Medical Genetics and Genomics 2013 policy paper suggesting that pathogenic mutations in 56 specified genes should be returned in the clinical setting has raised the question of whether comparable recommendations should be considered in research settings. The Clinical Sequencing Exploratory Research (CSER) Consortium and the Electronic Medical Records and Genomics (eMERGE) Network are multisite research programs that aim to develop practical strategies for addressing questions concerning the return of results in genomic research. CSER and eMERGE committees have identified areas of consensus regarding the return of genomic results to research participants. In most circumstances, if results meet an actionability threshold for return and the research participant has consented to return, genomic results, along with referral for appropriate clinical follow-up, should be offered to participants. However, participants have a right to decline the receipt of genomic results, even when doing so might be viewed as a threat to the participants' health. Research investigators should be prepared to return research results and incidental findings discovered in the course of their research and meeting an actionability threshold, but they have no ethical obligation to actively search for such results. These positions are consistent with the recognition that clinical research is distinct from medical care in both its aims and its guiding moral principles.

A survey of current practices for genomic sequencing test interpretation and reporting processes in US laboratories.

PURPOSE: While the diagnostic success of genomic sequencing expands, the complexity of this testing should not be overlooked. Numerous laboratory processes are required to support the identification, interpretation, and reporting of clinically significant variants. This study aimed to examine the workflow and reporting procedures among US laboratories to highlight shared practices and identify areas in need of standardization. METHODS: Surveys and follow-up interviews were conducted with laboratories offering exome and/or genome sequencing to support a research program or for routine clinical services. The 73-item survey elicited multiple choice and free-text responses that were later clarified with phone interviews. RESULTS: Twenty-one laboratories participated. Practices highly concordant across all groups included consent documentation, multiperson case review, and enabling patient opt-out of incidental or secondary findings analysis. Noted divergence included use of phenotypic data to inform case analysis and interpretation and reporting of case-specific quality metrics and methods. Few laboratory policies detailed procedures for data reanalysis, data sharing, or patient access to data. CONCLUSION: This study provides an overview of practices and policies of experienced exome and genome sequencing laboratories. The results enable broader consideration of which practices are becoming standard approaches, where divergence remains, and areas of development in best practice guidelines that may be helpful.Genet Med advance online publication 03 Novemeber 2016.

Return of individual research results and incidental findings: facing the challenges of translational science.

The debate over return of individual research results and incidental findings to study participants is a key frontier in research ethics and practice. This is fundamentally a problem of translational science-a question of when information about an individual that is generated in research should be communicated for clinical attention, particularly as technologies such as whole-genome sequencing and whole-exome sequencing are increasingly used in clinical care. There is growing consensus that investigators should offer participants at least those individual findings of high clinical importance and actionability. Increasing attention to what information biobanks and secondary researchers owe people who provide data and specimens offers an opportunity to treat these source individuals as research partners. Cutting-edge issues include return of results in pediatric populations and return to kin and family, both before and after the death of the proband, as well as how to manage incidental findings in clinical sequencing. Progress will require an understanding of the continuum linking research and clinical care and developing standards and models for return.

Addressing the ethical challenges in genetic testing and sequencing of children.

American Academy of Pediatrics (AAP) and American College of Medical Genetics (ACMG) recently provided two recommendations about predictive genetic testing of children. The Clinical Sequencing Exploratory Research Consortium's Pediatrics Working Group compared these recommendations, focusing on operational and ethical issues specific to decision making for children. Content analysis of the statements addresses two issues: (1) how these recommendations characterize and analyze locus of decision making, as well as the risks and benefits of testing, and (2) whether the guidelines conflict or come to different but compatible conclusions because they consider different testing scenarios. These statements differ in ethically significant ways. AAP/ACMG analyzes risks and benefits using best interests of the child and recommends that, absent ameliorative interventions available during childhood, clinicians should generally decline to order testing. Parents authorize focused tests. ACMG analyzes risks and benefits using the interests of the child and other family members and recommends that sequencing results be examined for additional variants that can lead to ameliorative interventions, regardless of age, which laboratories should report to clinicians who should contextualize the results. Parents must accept additional analysis. The ethical arguments in these statements appear to be in tension with each other.

Behind the Scenes: Facilitators and Barriers to Developing State Scarce Resource Allocation Plans for the COVID-19 Pandemic.

BACKGROUND: In response to COVID-19, many states revised, developed, or attempted to develop plans to allocate scarce critical care resources in the event that crisis standards of care were triggered. To our knowledge, no prior analysis has assessed this plan development process, including whether plans were successfully adopted. RESEARCH QUESTION: How did states develop or revise scarce resource allocation plans during the COVID-19 pandemic, and what were the barriers and facilitators to their development and adoption at the state level? STUDY DESIGN AND METHODS: Plan authors and state leaders completed a semistructured interview February to September 2022. Interview transcripts were qualitatively analyzed for themes related to plan development and adoption according to the principles of grounded theory. RESULTS: Thirty-six participants from 34 states completed an interview, from states distributed across all US regions. Among participants' states with plans that existed prior to 2020 (n = 24), 17 were revised and adopted in response to COVID-19. Six states wrote a plan de novo, with the remaining states failing to develop or adopt a plan. Thirteen states continued to revise their plans in response to disability or aging bias complaints or to respond to evolving needs. Many participants expressed that urgency in the early days of the pandemic prevented an ideal development process. Facilitators of successful plan development and adoption include: coordination or support from the state department of health and existing relationships with key community partners, including aging and disability rights groups and minoritized communities. Barriers include: lack of perceived political will to adopt a plan and development during a public health emergency. INTERPRETATION: To avoid repeating mistakes from the early days of the COVID-19 response, states should develop or revise plans with community engagement and consider maintaining a standing committee with diverse membership and content expertise to periodically review plans and advise state officials on pandemic preparedness.

Ethical, legal, and policy challenges in field-based neuroimaging research using emerging portable MRI technologies: guidance for investigators and for oversight.

Researchers are rapidly developing and deploying highly portable MRI technology to conduct field-based research. The new technology will widen access to include new investigators in remote and unconventional settings and will facilitate greater inclusion of rural, economically disadvantaged, and historically underrepresented populations. To address the ethical, legal, and societal issues raised by highly accessible and portable MRI, an interdisciplinary Working Group (WG) engaged in a multi-year structured process of analysis and consensus building, informed by empirical research on the perspectives of experts and the general public. This article presents the WG's consensus recommendations. These recommendations address technology quality control, design and oversight of research, including safety of research participants and others in the scanning environment, engagement of diverse participants, therapeutic misconception, use of artificial intelligence algorithms to acquire and analyze MRI data, data privacy and security, return of results and managing incidental findings, and research participant data access and control.

Recommendations for returning genomic incidental findings? We need to talk!

The American College of Medical Genetics and Genomics recently issued recommendations for reporting incidental findings from clinical whole-genome sequencing and whole-exome sequencing. The recommendations call for evaluating a specific set of genes as part of all whole-genome sequencing/whole-exome sequencing and reporting all pathogenic variants irrespective of patient age. The genes are associated with highly penetrant disorders for which treatment or prevention is available. The effort to generate a list of genes with actionable findings is commendable, but the recommendations raise several concerns. They constitute a call for opportunistic screening, through intentional effort to identify pathogenic variants in specified genes unrelated to the clinical concern that prompted testing. Yet for most of the genes, we lack evidence about the predictive value of testing, genotype penetrance, spectrum of phenotypes, and efficacy of interventions in unselected populations. Furthermore, the recommendations do not allow patients to decline the additional findings, a position inconsistent with established norms. Finally, the recommendation to return adult-onset disease findings when children are tested is inconsistent with current professional consensus, including other policy statements of the American College of Medical Genetics and Genomics. Instead of premature practice recommendations, we call for robust dialogue among stakeholders to define a pathway to normatively sound, evidence-based guidelines.