A new paradigm for investigating real-world social behavior and its neural underpinnings.

Eye tracking and other behavioral measurements collected from patient-participants in their hospital rooms afford a unique opportunity to study natural behavior for basic and clinical translational research. We describe an immersive social and behavioral paradigm implemented in patients undergoing evaluation for surgical treatment of epilepsy, with electrodes implanted in the brain to determine the source of their seizures. Our studies entail collecting eye tracking with other behavioral and psychophysiological measurements from patient-participants during unscripted behavior, including social interactions with clinical staff, friends, and family in the hospital room. This approach affords a unique opportunity to study the neurobiology of natural social behavior, though it requires carefully addressing distinct logistical, technical, and ethical challenges. Collecting neurophysiological data synchronized to behavioral and psychophysiological measures helps us to study the relationship between behavior and physiology. Combining across these rich data sources while participants eat, read, converse with friends and family, etc., enables clinical-translational research aimed at understanding the participants' disorders and clinician-patient interactions, as well as basic research into natural, real-world behavior. We discuss data acquisition, quality control, annotation, and analysis pipelines that are required for our studies. We also discuss the clinical, logistical, and ethical and privacy considerations critical to working in the hospital setting.

Bioethics in the Current Climate.

Drawing on insights from feminist epistemology and experience in genomics-related bioethics research, this essay offers three suggestions that may enable bioethics to contribute more persuasively to urgent issues affecting the health and well-being of individuals, communities, and the world they inhabit. First, it suggests that bioethics pay more attention to people's feelings, particularly those that help constitute their self-identities, and to the role of those feelings in their health-relevant behaviors. Further, it proposes conceiving of health-relevant behaviors expansively. Second, it suggests that bioethics advocate for a longer time horizon for the conduct of empirical bioethics research and other types of research addressing complex, systemic factors influencing health. Third, it suggests that bioethics play a larger role in illuminating and applauding the evolving nature of scientific knowledge.

Practices and Attitudes toward Returning Genomic Research Results to Low-Resource Research Participants.

INTRODUCTION: Many research programs are challenged to accommodate low-resource research participants' (LRRP) ancillary care needs when returning genomic research results. We define LRRP as those who are low income, uninsured, underinsured, or facing barriers to act upon the results returned. This study evaluates current policies and practices surrounding return of results (RoR) to LRRP, as well as the attitudes of investigators toward providing ancillary care to LRRP. METHODS: A semi-structured interview study was conducted with representatives of 35 genomic research programs nationwide. Eligible programs were returning, or planning to return, medically actionable genomic results to participants. RESULTS: Three content categories emerged from this study, including: (1) RoR structures, (2) barriers to RoR to LRRP, and (3) solutions to meet community and LRRP needs. Three major structures of RoR emerged: (1) RoR Embedded in Clinical Care, (2) RoR Independent of Clinical Care, and (3) Reliance on Clinical Partnerships to Facilitate RoR. Inadequacy of program resources to address the needs of LRRP was commonly considered a significant obstacle. The attitudes and views of informants regarding responsibility to provide ancillary care for LRRP receiving genomic results were highly varied. Some informants believed that genomic sequencing and testing was not a priority for LRRP because of other pressing issues in their lives, such as housing and food insecurity. Research programs differ regarding whether clinical and social support for LRRP is considered within the purview of the research team. Some programs instituted accommodations for LRRP, including social work referral and insurance enrollment assistance. CONCLUSION: Support to access downstream treatment is not readily available for LRRP in many genomic research programs. Development of best practices and policies for managing RoR to LRRP is needed.

The Ethics of Tobacco Harm Reduction: An Analysis of E-Cigarette Availability From the Perspectives of Utilitarianism, Bioethics, and Public Health Ethics.

Much evidence suggests e-cigarettes are substantially less harmful than combustible cigarettes. Assuming this is true, we analyze the ethical case for a policy of e-cigarette availability (ECA) as a tobacco harm reduction strategy. ECA involves making e-cigarettes available to allow smokers to switch to them, and informing smokers of the lower risks of e-cigarettes vis-à-vis smoking. After suggesting that utilitarian/consequentialist considerations do not provide an adequate ethical analysis, we analyze ECA using two other ethical frameworks. First, ECA is supported by a public health ethics framework. ECA is a population-level intervention consistent with respecting individual autonomy by using the least restrictive means to accomplish public health goals, and it supports equity and justice. Second, ECA is supported by four principles that form a biomedical ethics framework. By reducing smokers' health risks and not harming them, ECA fulfills principles of beneficence and non-maleficence. Because ECA allows smokers to make informed health decisions for themselves, it fulfills the principle requiring respect for persons and their autonomy. Here, we consider whether nicotine addiction and thus ECA undermine autonomy, and also discuss the ethical warrant for special protections for youth. Finally, ECA can also advance justice by providing a harm reduction alternative for disadvantaged groups that disproportionately bear the devastating consequences of smoking. Policies of differential taxation of cigarettes and e-cigarettes can facilitate adoption of less harmful alternatives by those economically disadvantaged. We conclude that public health and biomedical ethics frameworks are mutually reinforcing and supportive of ECA as a tobacco harm reduction strategy. Implications: Making e-cigarettes and information about them available is supported as ethical from multiple ethical perspectives.

Ethical Practices and Legal Challenges in Mental Health Research.

Considerations of justice and concern for well-being support conducting mental health research and addressing ethical concerns specific to mental health research are critical. We discuss these concerns, provide recommendations to enable the ethical conduct of mental health research, and argue that participants' interests should be given primary weight in resolving apparent dilemmas. We also comment on provisions of two legislative actions in India relevant to mental health research: Rights of Persons with Disability Act 2016 and the Mental Health Care Act 2017. Both conform to the 2006 United Nations Convention on Rights of Persons with Disabilities of which India is a signatory. Both provide protections and enumerate rights relevant to people with mental health conditions but with differing focus. The commonalities and differences between the three are discussed in the background of international literature on research in mental health conditions. Studies involving deception and future directions for ethical requirements regarding genetic research are discussed.

Why Quality-of-Life Data Collection and Use Should Be Standardized When Evaluating Candidates for Hand Transplantation.

This article argues for 3 mutually reinforcing interventions in the field of hand transplantation (HTx): (1) collection of qualitative data about hand transplant recipients' subjective quality of life (QoL) outcomes, (2) multicenter standardization of data collection, and (3) use of data to develop evidence-based, standardized protocols for HTx candidate evaluation and information disclosure. These interventions are needed to improve candidate evaluation and informed consent processes in HTx, wherein the highly personal nature of desired outcomes justifies holding a candidate's consent to a standard approaching authenticity rather than the usual minimal standard of being informed and voluntary.

Research Use of Ecological Momentary Assessment for Adverse Event Monitoring Following Amyloid-ß Results Disclosure.

As calls for transparency in human subjects research grow, investigators conducting Alzheimer's disease (AD) biomarker research are increasingly required to consider their ethical obligations regarding the return of AD biomarker test results to research participants. When disclosing these test results to potentially vulnerable participants, investigators may face unique challenges to identify adverse events, particularly psychological events. The purpose of this paper is to describe our research team's experience with developing and implementing a process for enhanced adverse event monitoring following the return of amyloid-ß (Aß) imaging results to research participants with mild cognitive impairment (MCI). Ethical and logistical considerations are presented along with preliminary findings from an ongoing randomized controlled trial of Aß imaging results disclosure in MCI. Following receipt of amyloid imaging results, participants underwent 14 days of adverse event monitoring using ecological momentary assessment (EMA), a strategy to capture health, behaviors, and mood as they occur in participants' natural settings in real time. EMA telephone calls were placed at random during waking hours to screen for mood changes. Investigators were alerted for positive depression, anxiety, suicidal ideation screenings, or for two days of failed call attempts. Preliminary feasibility of twenty-four participants with MCI who participated in EMA mood assessments was successfully completed 83% (SD = 0.4) of the time over 14 days with no alerts for anxiety or depression screening items. EMA, when used with standard adverse event monitoring, is a promising and novel approach to maximize early detection of negative psychological reactions following AD biomarker results disclosed in research settings.

Narrative methods for assessing "quality of life" in hand transplantation: five case studies with bioethical commentary.

Despite having paved the way for face, womb and penis transplants, hand transplantation today remains a small hybrid of reconstructive microsurgery and transplant immunology. An exceptionally limited patient population internationally (N < 200) complicates medical researchers' efforts to parse outcomes "objectively." Presumed functional and psychosocial benefits of gaining a transplant hand must be weighed in both patient decisions and bioethical discussions against the difficulty of adhering to post-transplant medications, the physical demands of hand transplant recovery on the patient, and the serious long-term health risks of immunosuppressant drugs. This paper relates five narratives of hand transplantation drawn from an oral history project to show how narrative methods can and should inform ethical evaluations and the clinical process of hand transplantation. The interviews with patients and their partners analyzed here lead us to suggest that qualitative accounts of patient experiences should be used to complement clinical case studies reported in medical journals and to help develop instruments to assess outcomes more systematically.

Normative and conceptual ELSI research: what it is, and why it's important.

The Ethical, Legal, and Social Implications (ELSI) Research Program of the National Human Genome Research Institute sponsors research examining ethical, legal, and social issues arising in the context of genetics/genomics. The ELSI Program endorses an understanding of research not as the sole province of empirical study, but instead as systematic study or inquiry, of which there are many types and methods. ELSI research employs both empirical and nonempirical methods. Because the latter remain relatively unfamiliar to biomedical and translational scientists, this paper seeks to elucidate the relationship between empirical and nonempirical methods in ELSI research. It pays particular attention to the research questions and methods of normative and conceptual research, which examine questions of value and meaning, respectively. To illustrate the distinct but interrelated roles of empirical and nonempirical methods in ELSI research, including normative and conceptual research, the paper demonstrates how a range of methods may be employed both to examine the evolution of the concept of incidental findings (including the recent step toward terming them 'secondary findings'), and to address the normative question of how genomic researchers and clinicians should manage incidental such findings.

'Recurrent losers unite': Online forums, evidence-based activism, and pregnancy loss.

Women with recurrent pregnancy loss face unique challenges associated with the social invisibility of their condition, patchy medical knowledge about it, and often intransigent positions of doctors. We approach online forums as sites of knowledge production and examine discussions among women with recurrent miscarriages. We observe that some forum participants gather, summarize, and share experience-based and research-based information in order to challenge certain medical conceptions. We describe these efforts as an example of individual patients' evidence-based activism enabled by new media platforms and other technoscientific tools available to the public.

A qualitative study of Institutional Ethics Committees: Members' understanding of research guidelines, privacy, and challenges to privacy protection.

Right to privacy of health-related information is a foundational bioethical principle. In India, the importance of protecting privacy is included in law and ethical guidelines. Institutional Ethics Committees (IECs) are entrusted with the responsibility of protecting fundamental ethical principles, including privacy and confidentiality. The present qualitative study was designed to understand IECs' privacy-related obligations and the members' experience in implementing ethical guidelines and privacy protections in their institutions. An interview guide was prepared regarding knowledge of ethical guidelines. Interviews of nineteen IEC members were recorded, transcribed, and translated. Interviews were analysed using thematic analysis. Themes related to these issues were extracted after analysis: awareness, understanding, and implementation of ethical guidelines; understanding of privacy-related obligations and their implementation; and juridical risks to privacy of patients and research participants. The results suggest that training programmes and awareness workshops should be organised for IEC members to protect the rights of research participants, especially in confidentiality issues.

Caring for Patients or Organs: New Therapies Raise New Dilemmas in the Emergency Department.

Two potentially lifesaving protocols, emergency preservation and resuscitation (EPR) and uncontrolled donation after circulatory determination of death (uDCDD), currently implemented in some U.S. emergency departments (EDs), have similar eligibility criteria and initial technical procedures, but critically different goals. Both follow unsuccessful cardiopulmonary resuscitation and induce hypothermia to "buy time": one in trauma patients suffering cardiac arrest, to enable surgical repair, and the other in patients who unexpectedly die in the ED, to enable organ donation. This article argues that to fulfill patient-focused fiduciary obligations and maintain community trust, institutions implementing both protocols should adopt and publicize policies to guide ED physicians to utilize either protocol for particular patients, in order to address the appearance of conflict of interest arising from the protocols' similarities. It concludes by analyzing ethical implications of incentives that may influence institutions to develop the expertise required for uDCDD but not EPR.

The Precision Medicine Initiative's All of Us Research Program: an agenda for research on its ethical, legal, and social issues.

The Precision Medicine Initiative (PMI) is an innovative approach to developing a new model of health care that takes into account individual differences in people's genes, environments, and lifestyles. A cornerstone of the initiative is the PMI All of Us Research Program (formerly known as PMI-Cohort Program) which will create a cohort of 1 million volunteers who will contribute their health data and biospecimens to a centralized national database to support precision medicine research. The PMI All of US Research Program is the largest longitudinal study in the history of the United States. The designers of the Program anticipated and addressed some of the ethical, legal, and social issues (ELSI) associated with the initiative. To date, however, there is no plan to call for research regarding ELSI associated with the Program-PMI All of Us program. Based on analysis of National Institutes of Health (NIH) funding announcements for the PMI All of Us program, we have identified three ELSI themes: cohort diversity and health disparities, participant engagement, and privacy and security. We review All of Us Research Program plans to address these issues and then identify additional ELSI within each domain that warrant ongoing investigation as the All of Us Research Program develops. We conclude that PMI's All of Us Research Program represents a significant opportunity and obligation to identify, analyze, and respond to ELSI, and we call on the PMI to initiate a research program capable of taking on these challenges.Genet Med advance online publication 01 December 2016.

Development of a Standardized Approach to Disclosing Amyloid Imaging Research Results in Mild Cognitive Impairment.

The increased use of PET amyloid imaging in clinical research has sparked numerous concerns about whether and how to return such research test results to study participants. Chief among these is the question of how best to disclose amyloid imaging research results to individuals who have cognitive symptoms that could impede comprehension of the information conveyed. We systematically developed and evaluated informational materials for use in pre-test counseling and post-test disclosures of amyloid imaging research results in mild cognitive impairment (MCI). Using simulated sessions, persons with MCI and their family care partners (N = 10 dyads) received fictitious but realistic information regarding brain amyloid status, followed by an explanation of how results impact Alzheimer's disease risk. Satisfaction surveys, comprehension assessments, and focus group data were analyzed to evaluate the materials developed. The majority of persons with MCI and their care partners comprehended and were highly satisfied with the information presented. Focus group data reinforced findings of high satisfaction and included 6 recommendations for practice: 1) offer pre-test counseling, 2) use clear graphics, 3) review participants' own brain images during disclosures, 4) offer take-home materials, 5) call participants post-disclosure to address emerging questions, and 6) communicate seamlessly with primary care providers. Further analysis of focus group data revealed that participants understood the limitations of amyloid imaging, but nevertheless viewed the prospect of learning one's amyloid status as valuable and empowering.

Advancing Pharmacogenomics Education in the Core PharmD Curriculum through Student Personal Genomic Testing.

OBJECTIVE: To develop, implement, and evaluate "Test2Learn" a program to enhance pharmacogenomics education through the use of personal genomic testing (PGT) and real genetic data. DESIGN: One hundred twenty-two second-year doctor of pharmacy (PharmD) students in a required course were offered PGT as part of a larger program approach to teach pharmacogenomics within a robust ethical framework. The program added novel learning objectives, lecture materials, analysis tools, and exercises using individual-level and population-level genetic data. Outcomes were assessed with objective measures and pre/post survey instruments. ASSESSMENT: One hundred students (82%) underwent PGT. Knowledge significantly improved on multiple assessments. Genotyped students reported a greater increase in confidence in understanding test results by the end of the course. Similarly, undergoing PGT improved student's self-perceived ability to empathize with patients compared to those not genotyped. Most students (71%) reported feeling PGT was an important part of the course, and 60% reported they had a better understanding of pharmacogenomics specifically because of the opportunity. CONCLUSION: Implementation of PGT in the core pharmacy curriculum was feasible, well-received, and enhanced student learning of pharmacogenomics.

Prenatal whole-exome sequencing: parental attitudes.

OBJECTIVE: The aim of this study was to survey the opinions of expectant parents regarding prenatal whole-exome sequencing. METHODS: The study used a questionnaire that focused on acceptability of prenatal whole-exome sequencing to individuals who pursued first-trimester prenatal screening in a tertiary academic medical center. A total of 186 expectant individuals completed the questionnaire. The results of the questionnaire were analyzed using descriptive statistics and logistic regression models. RESULTS: Eighty-three percent of the participants answered that prenatal whole-exome sequencing should be offered, 14.8% were neutral, and only 2.2% disagreed. Fifty-four percent of the participants were interested in having prenatal whole-exome sequencing for their fetus, 40.1% were neutral, and 6.6% disagreed. The majority of participants expressed a desire to know about treatable (96.2%) and non-treatable (86.3%) childhood conditions, and most said the same for treatable (76.0%) and non-treatable (74.3%) adult-onset conditions. Over half of the participants (59.7%) indicated a maximum acceptable turnaround time of 3 weeks or less for prenatal whole-exome sequencing. CONCLUSIONS: The majority of respondents felt prenatal whole-exome sequencing should be offered. Moreover, the majority wanted to know prenatally about treatable and non-treatable childhood and adult conditions.

Sickle Cell Trait Screening of Collegiate Athletes: Ethical Reasons for Program Reform.

The National Collegiate Athletic Association (NCAA) requires all student-athletes have their sickle cell trait (SCT) status confirmed prior to athletic participation. The NCAA approved the screening program in 2010 for institutions participating in Division I athletics and extended it in subsequent years to institutions at Division II and III levels. Ethical concerns about the controversial policy focus on its mandatory nature and potential impact on student-athletes, particularly through stigmatization of and discrimination against those with SCT. Organizations, such as the American Society of Hematology (ASH), oppose the imposition of SCT testing and instead recommend universal precautions that would protect the entire student-athlete population without revealing student-athletes' SCT statuses. This paper discusses these issues and offers recommendations, including genetic counseling, which would improve the current SCT screening program. It argues that implementation of universal precautions would ensure that the most ethically sound practices are afforded to every student-athlete.