Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

Patients' Reactions to Letters Communicating Collateral Findings of Pragmatic Clinical Trials: a National Web-Based Survey.

BACKGROUND: Collateral findings in pragmatic clinical trials are findings that may have implications for patients' health but were not generated to address a trial's primary research questions. It is uncertain how best to communicate these collateral findings to patients. OBJECTIVES: To determine how reactions to a letter communicating collateral findings relate to who signed the letter, the type of finding, or whether the letter specified that the finding arose from a pragmatic clinical trial. RESEARCH DESIGN: Web-based survey experiment using a between-subjects design in which respondents were randomly assigned within education strata to view and respond to 1 of 16 hypothetical scenarios. SUBJECTS: Adults recruited from an online panel constructed from a probability sample of US-based postal addresses. MEASURES: The primary outcomes were the action the respondent would take next (i.e., contact a doctor immediately or something else) and the respondent's emotional reactions (i.e., all positive, all negative, mixed, or none). RESULTS: A total of 4080 respondents had analyzable data. Although some effects were statistically significant (P < .05), none exceeded a prespecified threshold for policy relevance (15 or more percentage points). Ratings of letter clarity and level of understanding were lower for letters that included a description of the clinical trial. CONCLUSIONS: Signatory and level of detail about collateral findings did not substantially affect people's intentions to take the recommended action of contacting their doctor. Deciding whether to include a description of the pragmatic clinical trial requires a trade-off between transparency and more difficulty understanding the contents of the letter.

Patients' Views About the Disclosure of Collateral Findings in Pragmatic Clinical Trials: a Focus Group Study.

BACKGROUND: Pragmatic clinical trials (PCTs) are increasingly being conducted to efficiently generate evidence to inform healthcare decision-making. Despite their growing acceptance, PCTs may involve a variety of ethical issues, including the management of pragmatic clinical trial-collateral findings (PCT-CFs), that is, information that emerges in PCTs that is unrelated to the primary research questions but may have implications for patients, clinicians, and health systems. OBJECTIVE: We sought to understand patients' views about PCT-CF disclosure, including how, by whom, and the nature and extent of information provided. DESIGN: Prospective, qualitative focus group study. PARTICIPANTS: Focus groups were conducted in Baltimore, MD; Houston, TX; and Seattle, WA (overall N = 66), during July and August 2019. APPROACH: All groups discussed a hypothetical scenario involving the detection of a PCT-CF of contraindicated medications. Participants were asked about their reactions to the PCT-CF and issues related to its disclosure. KEY RESULTS: Reactions to learning about the PCT-CF were mixed, ranging from fear of a significant health problem, anger that the contraindicated medications had gone unnoticed and/or for being included in research without their permission, to gratitude for the information. Preferences for how such disclosures are made varied but were driven by several consistent desires, namely minimizing patient harm and anxiety and demonstrating trust and respect. Many wanted their treating clinician to be informed of the PCT-CF so that they would be prepared to answer patients' questions and to discuss treatment options. CONCLUSIONS: The detection of PCT-CFs is likely to increase with further expansion of PCTs. As such, clinicians will undoubtedly become involved in the management of PCT-CFs. Our data illustrate some of the challenges clinicians may face when their patients are informed of a PCT-CF and the need to develop guidance for disclosing PCT-CFs in ways that align with patients' preferences and values.

Secondary Use of Patient Tissue in Cancer Biobanks.

BACKGROUND: As scientific techniques evolve, historical informed consent forms may inadequately address modern research proposals, leading to ethical questions regarding research with archived biospecimens. SUBJECTS, MATERIALS, AND METHODS: We conducted focus groups among patients with cancer recruited from Massachusetts General Hospital to explore views on medical research, biobanking, and scenarios based on real biospecimen research dilemmas. Our multidisciplinary team developed a structured focus group guide, and all groups were recorded and transcribed. Transcripts were coded for themes by two independent investigators using NVivo software. RESULTS: Across five focus groups with 21 participants, we found that most participants were supportive of biobanks and use of their own tissue to advance scientific knowledge. Many favor allowing research beyond the scope of the original consent to proceed if recontact is impossible. However, participants were not comfortable speaking for other patients who may oppose research beyond the original consent. This was viewed as a potential violation of participants' rights or interests. Participants were also concerned with a "slippery slope" and potential scientific abuse if research were permitted without adherence to original consent. There was strong support for recontact and reconsent when possible and for the concept of broad consent at the time of tissue collection. CONCLUSION: Our participants support use of their tissue to advance research and generally support any productive scientific approach. However, in the absence of broad initial consent, when recontact is impossible, a case-by-case decision must be made regarding a proposal's potential benefits and harms. Many participants support broad use of their tissue, but a substantial minority object to use beyond the original consent. IMPLICATIONS FOR PRACTICE: For prospective studies collecting tissue for future research, investigators should consider seeking broad consent, to allow for evolution of research questions and methods. For studies using previously collected tissues, researchers should attempt recontact and reconsent for research aims or methods beyond the scope of the original consent. When reconsent is not possible, a case-by-case decision must be made, weighing the scientific value of the biobank, potential benefits of the proposed research, and the likelihood and nature of risks to participants and their welfare interests. This study's data suggest that many participants support broad use of their tissue and prefer science to move forward.

Perspectives on Genetic Testing and Return of Results from the First Cohort of Presymptomatically Tested Individuals At Risk of Huntington Disease.

This qualitative study gathered opinions about genetic testing from people who received presymptomatic testing for Huntington's disease (HD) 20-30 years ago and have lived with the implications of that testing for decades. During the last section of a semi-structured interview, participants were asked open-ended questions about their opinions on the importance of autonomy in the decision to be tested for HD, whether a formal HD testing protocol is necessary, whether physician ordering for HD is acceptable without a formal protocol, whether online direct-to-consumer (DTC) genetic testing for HD is acceptable, and whether incidental/secondary findings should be returned in the context of whole exome/genome sequencing. Most-but not all-participants were in favor of an individual's right to decide whether and when to pursue HD testing, use of a formal HD testing protocol, and returning medically actionable secondary findings. However, the majority of participants were opposed not only to physician ordering and DTC HD testing in the absence of a formal protocol but also to returning a secondary finding of an expanded HD allele. This study presents the opinions of a unique and extremely well-informed cohort on issues that need to be taken into careful consideration by genetic counselors and other medical professionals who are developing genetic testing protocols, making decisions about the availability of genetic tests, and making decisions about whether and how to return incidental findings.

The Therapeutic "Mis"conception: An Examination of its Normative Assumptions and a Call for its Revision.

Dissecting Bioethics, edited by Tuija Takala and Matti Hayry, welcomes contributions on the conceptual and theoretical dimensions of bioethics. The department is dedicated to the idea that words defined by bioethicists and others should not be allowed to imprison people's actual concerns, emotions, and thoughts. Papers that expose the many meanings of a concept, describe the different readings of a moral doctrine, or provide an alternative angle to seemingly self-evident issues are particularly appreciated. To submit a paper or to discuss a suitable topic, contact Tuija Takala at tuija.takala@helsinki.fi.

Beyond consent in research. Revisiting vulnerability in deep brain stimulation for psychiatric disorders.

Vulnerability is an important criterion to assess the ethical justification of the inclusion of participants in research trials. Currently, vulnerability is often understood as an attribute inherent to a participant by nature of a diagnosed condition. Accordingly, a common ethical concern relates to the participant's decisionmaking capacity and ability to provide free and informed consent. We propose an expanded view of vulnerability that moves beyond a focus on consent and the intrinsic attributes of participants. We offer specific suggestions for how relational aspects and the dynamic features of vulnerability could be more fully captured in current discussions and research practices.

Blurring Boundaries: A Proposed Research Agenda for Ethical, Legal, Social, and Historical Studies at the Intersection of Infectious and Genetic Disease.

Contemporary understanding of the mechanisms of disease increasingly points to examples of "genetic diseases" with an infectious component and of "infectious diseases" with a genetic component. Such blurred boundaries generate ethical, legal, and social issues and highlight historical contexts that must be examined when incorporating host genomic information into the prevention, outbreak control, and treatment of infectious diseases.

Designing robots that do no harm: understanding the challenges of Ethics for Robots.

This article describes key challenges in creating an ethics "for" robots. Robot ethics is not only a matter of the effects caused by robotic systems or the uses to which they may be put, but also the ethical rules and principles that these systems ought to follow-what we call "Ethics for Robots." We suggest that the Principle of Nonmaleficence, or "do no harm," is one of the basic elements of an ethics for robots-especially robots that will be used in a healthcare setting. We argue, however, that the implementation of even this basic principle will raise significant challenges for robot designers. In addition to technical challenges, such as ensuring that robots are able to detect salient harms and dangers in the environment, designers will need to determine an appropriate sphere of responsibility for robots and to specify which of various types of harms must be avoided or prevented. These challenges are amplified by the fact that the robots we are currently able to design possess a form of semi-autonomy that differs from other more familiar semi-autonomous agents such as animals or young children. In short, robot designers must identify and overcome the key challenges of an ethics for robots before they may ethically utilize robots in practice.

Genomic testing in voluntary workplace wellness programs in the US: Evidence and challenges.

BACKGROUND: Workplace genetic and/or genomic testing (wGT) is one of many options that employers can offer within the scope of voluntary workplace wellness programs, though we know little about how many employers are offering this benefit, or what kinds of testing are included. METHODS: Our landscaping review sought to discover the prevalence and distribution of wGT within voluntary wellness programs among U.S. companies using three approaches: (1) analysis of publicly available information; (2) national surveys; and (3) interviews with company representatives. RESULTS: In total, 50/420 (11.9%) companies we investigated had publicly available data suggesting that they offer wGT to their employees. Survey data weighted to be representative of the type and distribution of U.S. companies suggest that ~1% of U.S. companies offer wGT to their employees. CONCLUSION: Our research found little evidence of broad uptake of wGT among U.S. companies, though information gathering was challenging.

Get law enforcement out of biospecimen authentication.

Use of D NA markers in research that are used in law enforcement risks undermining public trust and participation.

Voluntary workplace genomic testing: wellness benefit or Pandora's box?

Consumer interest in genetic and genomic testing is growing rapidly, with more than 26 million Americans having purchased direct-to-consumer genetic testing services. Capitalizing on the increasing comfort of consumers with genetic testing outside the clinical environment, commercial vendors are expanding their customer base by marketing genetic and genomic testing services, including testing for pharmacogenomic and pathogenic variants, to employers for inclusion in workplace wellness programs. We describe the appeal of voluntary workplace genomic testing (wGT) to employers and employees, how the ethical, legal, and social implications literature has approached the issue of genetic testing in the workplace in the past, and outline the relevant legal landscape. Given that we are in the early stages of development of the wGT market, now is the time to identify the critical interests and concerns of employees and employers, so that governance can develop and evolve along with the wGT market, rather than behind it, and be based on data, rather than speculative hopes and fears.

Deep brain stimulation, personal identity and policy.

A range of implantable brain-interfacing devices (IBIDs) is currently in use and development for the treatment of movement disorders and disorders of mood, behaviour and thought. These include cochlear implants, deep brain stimulation (DBS), prosthetic limbs, and optogenetic interventions (the combined use of genetics and optics to control individual cells). While implantable non-brain devices, such as implantable cardioverter defibrillators, began receiving US Food and Drug Administration approval in 1980, the development of IBIDs is recent, with the approval of DBS for Parkinson's disease in 1997. The expansion in use of IBIDs from neurological to psychiatric conditions is even more recent, with current trials underway for a range of disorders including depression, OCD, addiction, Alzheimer's disease and Tourette's syndrome. Emerging applications of existing IBIDs and new devices in development differ from currently approved devices and applications in two potentially crucial ways: 1) They target conditions traditionally seen as psychiatric; and/or 2) They target and modify functions or traits tied closely to agency, personal identity and personhood. As such, understanding patients' and caregivers' conceptions of personal identity in the context of disease and treatment is important not only for the informed consent process, but also for questions of public policy.

Stakeholder perspectives regarding pragmatic clinical trial collateral findings.

CONTEXT: Pragmatic clinical trials (PCTs), which are becoming widespread since they are relatively inexpensive and offer important benefits for healthcare decision-making, can also present practical, ethical, and legal challenges. One such challenge involves managing "pragmatic clinical trial collateral findings" (PCT-CFs), or information emerging in a PCT that is unrelated to the primary research question(s), yet may have implications for individual patients, clinicians, or health care systems from whom or within which data were collected. The expansion of PCTs makes it likely healthcare systems will increasingly encounter PCT-CFs, yet little guidance exists regarding their appropriate management. METHODS: We conducted semi-structured interviews with key stakeholders experienced in the conduct or oversight of PCTs and those in health system leadership. Interviews explored respondents' experience with PCTs and PCT-CFs, and actual or hypothetical reactions to PCT-CF management. We used standard methods of qualitative analysis to identify key themes. FINDINGS: Forty-one stakeholders participated. Four key themes emerged. First, discussions of PCT-CFs are complicated by layers of ambiguity related to both the nature of PCTs themselves, and unanticipated results that emanate from them. Second, management of PCT-CFs is context-specific, and not amenable to a "one-size-fits-all" approach. Third, there was a wide diversity of attitudes regarding the scope of researcher responsibilities in PCTs. Fourth, PCT-CFs had generally not been previously considered by respondents, but there was widespread belief in the importance of prospective planning to anticipate such issues in future PCTs. CONCLUSIONS: PCT-CFs are likely to increase, yet those charged with PCT-CF decision-making and their disclosure are unlikely to have experience with these issues. Further deliberation about the ethical obligations and implementation processes regarding PCT-CFs is needed. To enhance the likelihood of developing sound policies and practices, such deliberations should include the input and perspectives of key stakeholders in PCTs, including professionals, policy makers, and patients.

Identification and management of pragmatic clinical trial collateral findings: A current understanding and directions for future research.

While the embedded nature of pragmatic clinical trials (PCTs) can improve the efficiency and relevance of research for multiple stakeholders, embedding research into ongoing clinical care can also involve ethical and regulatory challenges. An emergent challenge is the management of pragmatic clinical trial collateral findings (PCT-CFs). While PCT-CFs share some features with incidental or secondary findings that are encountered in conventional clinical trials and clinical care, the PCT context differs in ethically relevant ways that complicate PCT-CF identification and management. We report on the results of a two-year multi-method investigation of PCT-CFs. Overall, five core themes emerged: 1) the liminal nature of PCTs and the implications of this for PCT-CFs; 2) the context-specific nature of PCT-CF management; 3) the centrality of institutions; 4) the importance of prospective planning; and 5) patient expectations. Among the central lessons of this work are that prior ethics guidance from other settings cannot easily be adapted to address PCT-CFs, nor can a single approach readily accommodate all PCT-CFs. Moving forward, stakeholders, including researchers, institutions, ethics oversight bodies, and funders, should anticipate and plan for PCT-CFs in the design, conduct, and analysis of PCTs. Future scholarship is needed to examine experiences with PCT-CFs, and the practical and conceptual issues they raise for the future conduct of PCTs.

Employees' Views and Ethical, Legal, and Social Implications Assessment of Voluntary Workplace Genomic Testing.

Employers have begun to offer voluntary workplace genomic testing (wGT) as part of employee wellness benefit programs, but few empirical studies have examined the ethical, legal, and social implications (ELSI) of wGT. To better understand employee perspectives on wGT, employees were surveyed at a large biomedical research institution. Survey respondents were presented with three hypothetical scenarios for accessing health-related genomic testing: via (1) their doctor; (2) their workplace; and 3) a commercial direct-to-consumer (DTC) genetic testing company. Overall, 594 employees (28%) responded to the survey. Respondents indicated a preference for genomic testing in the workplace setting (70%; 95% CI 66-74%), followed by doctor's office (54%; 95% CI 50-58%), and DTC testing (20%; 95% CI 17-24%). Prior to participating in wGT, respondents wanted to know about confidentiality of test results (79%), existence of relevant laws and policies (70%), and privacy protection (64%). Across scenarios, 92% of respondents preferred to view the test results with a genetic counselor. These preliminary results suggest that many employees are interested and even prefer genetic testing in the workplace and would prefer testing with support from genetic health professionals. Confirmation in more diverse employer settings will be needed to generalize such findings.

Medicine on the fringe: stem cell-based interventions in advance of evidence.

Stem cell-based interventions (SCBIs) offer great promise; however, there is currently little internationally accepted, scientific evidence supporting the clinical use of SCBIs. The consensus within the scientific community is that a number of hurdles still need to be cleared. Despite this, SCBIs are currently being offered to patients. This article provides a content analysis of materials obtained from SCBI providers. We find content that strains credulity and almost no evidence of SCBIs being delivered in the context of clinical trials. We conclude that until scientific evidence is available, as a general rule, providers should only offer SCBIs in the context of controlled clinical trials. Clients should be aware that the risks and benefits of SCBIs are unknown, that their participation is unlikely to advance scientific knowledge, and they are likely to become ineligible to participate in future clinical trials of SCBIs. We recommend steps to promote patient education and enhance global oversight.