The Promise and Reality of Public Engagement in the Governance of Human Genome Editing Research.

This paper analyses the activities of five organizations shaping the debate over the global governance of genome editing in order to assess current approaches to public engagement (PE). We compare the recommendations of each group with its own practices. All recommend broad engagement with the general public, but their practices vary from expert-driven models dominated by scientists, experts, and civil society groups to citizen deliberation-driven models that feature bidirectional consultation with local citizens, as well as hybrid models that combine elements of both approaches. Only one group practices PE that seeks community perspectives to advance equity. In most cases, PE does little more than record already well-known views held by the most vocal groups, and thus is unlikely to produce more just or equitable processes or policy outcomes. Our exploration of the strengths, weaknesses, and possibilities of current forms of PE suggests a need to rethink both "public" and "engagement."

Reconsidering scarce drug rationing: implications for clinical research.

Hospital systems commonly face the challenge of determining just ways to allocate scarce drugs during national shortages. There is no standardised approach of how this should be instituted, but principles of distributive justice are commonly used so that patients who are most likely to benefit from the drug receive it. As a result, clinical indications, in which the evidence for the drug is assumed to be established, are often prioritised over research use. In this manuscript, we present a case of a phase II investigational trial of intravenous thiamine for delirium prevention in patients undergoing haematopoietic stem cell transplantation to emphasise several shortcomings in the overarching prioritisation of clinical over research uses of scarce drugs. Specifically, we present the following considerations: (1) clinical use may not have stronger evidence than research use; (2) a strong scientific rationale for research use may outweigh the claim for clinical indications in which there is weak evidence; (3) treatment within the context of a clinical trial may be the standard of care; and (4) research use may not only benefit patients receiving the treatment but also offers the prospect of improving future clinical care. In summary, we argue against allocation schemes that prohibit all research uses of scarce drugs and instead recommend that allocation schemes include a balanced approach that weighs risks and benefits of access to scarce drugs irrespective of the research versus clinical use designation.

Clarifying a Clinical Ethics Service's Value, the Visible and the Hidden.

Our aim in this article is to define the difficulties that clinical ethics services encounter when they are asked to demonstrate the value a clinical ethics service (CES) could and should have for an institution and those it serves. The topic emerged out of numerous related presentations at the Un-Conference hosted by the Cleveland Clinic in August 2018 that identified challenges of articulating the value of clinical ethics work for hospital administrators. After a review these talks, it was apparent that the field of clinical ethics may be at a crisis of sorts due to increased pressure to provide explicit measures to healthcare institutions to concretely demonstrate that CESs make a valuable difference in healthcare delivery. In this article we grapple with how to satisfy the need for demonstrable value in a field in which metrics alone may not capture the scope of clinical ethics practice. We suggest that capturing the value of a CES has been difficult because the benefits of ethics consultation may be overt or attributable to the CES, but are often hidden due to the systems-level and process-oriented nature of clinical ethics work. Part of the difficulty in demonstrating the value of CESs is capturing and conveying all of the ways the integration of a CES throughout an institution positively affects patients, families, visitors, healthcare professionals, administrators, and the institution itself. Our aim is to (1) elucidate the multifaceted value added by a CES, including value that tends to be hidden and (2) suggest how to demonstrate value to others in a way that is not simplistic or reductionistic.

Transitions in Care for Infants with Trisomy 13 or 18.

Background and Objectives The scope of interventions offered to infants with trisomy 13 (T13) or trisomy 18 (T18) is increasing. We describe the spectrum of care provided, highlighting transitions in care for individual patients. Patients and Methods This is a single-center, retrospective cohort of infants with T13 or T18 born between 2004 and 2015. Initial care was classified as comfort care or intervention using prenatal counseling notes. Transitions in care were identified in the medical record. Results In this study, 25 infants were divided into two groups based on their care: neonates who experienced no transition in care and neonates who experienced at least one transition. Eleven neonates experienced no transition in care with 10 receiving comfort care. Fourteen neonates experienced at least one transition: three transitioned from comfort care to intervention and 11 from intervention to comfort care. The three initially provided comfort care were discharged home with hospice and readmitted. Among the 11 cases who transitioned from intervention to comfort care, 9 transitioned during the birth hospitalization, 6 had no prenatal suspicion for T13 or T18, and 5 experienced elective withdrawal of intensive care. Conclusion The spectrum of care for infants with T13 or T18 illustrates the need for individualized counseling that is on-going, goal directed, collaborative, and responsive.

Looking for Trouble: Preventive Genomic Sequencing in the General Population and the Role of Patient Choice.

Advances in genomics have led to calls for developing population-based preventive genomic sequencing (PGS) programs with the goal of identifying genetic health risks in adults without known risk factors. One critical issue for minimizing the harms and maximizing the benefits of PGS is determining the kind and degree of control individuals should have over the generation, use, and handling of their genomic information. In this article we examine whether PGS programs should offer individuals the opportunity to selectively opt out of the sequencing or analysis of specific genomic conditions (the menu approach) or whether PGS should be implemented using an all-or-nothing panel approach. We conclude that any responsible scale-up of PGS will require a menu approach that may seem impractical to some, but that draws its justification from a rich mix of normative, legal, and practical considerations.

The public-private research ecosystem in the genome editing era.

Biomedical research in the US has long been conducted in a public-private (PP) "ecosystem." Today, especially with gene therapies and genome editing-based medicine, publicly funded researchers frequently hand off their research to the private sector for clinical development, often to small, venture capital-funded startups in which they have a financial interest. This trend raises ethical questions about conflicts of interest, effectiveness of regulatory oversight, and justice in therapy access, that we are addressing in a multi-year, multidisciplinary study of the evolving governance of genome editing. This paper draws on interviews with scientists working across the PP divide and their private sector business and financial partners. We find little concern about potential ethical dilemmas, with two exceptions expressed by public sector scientists: concerns about inequitable access to treatments due to disparities in wealth, ethnicity, and health insurance benefits; and about whether their private collaborators' profit motive may affect their research objectives.

"Death and Taxes": Why Financial Compensation for Research Participants is an Economic and Legal Risk.

In the US, research payments are technically taxable income. This article argues that tax liability is a form of possible economic and legal risk of paid research participation. Findings are presented from empirical research on Phase I healthy volunteer trials. The article concludes by discussing the implications of these findings for the informed consent process, as well as for broader ethical issues in whether and how payments for research participation should be regulated.

Recommendations for ethical approaches to genotype-driven research recruitment.

Recruiting research participants based on genetic information generated about them in a prior study is a potentially powerful way to study the functional significance of human genetic variation. However, it also presents significant ethical challenges that, to date, have received only minimal consideration. We convened a multi-disciplinary workshop to discuss key issues relevant to the conduct and oversight of genotype-driven recruitment and to translate those considerations into practical policy recommendations. Workshop participants were invited from around the US, and included genomic researchers and study coordinators, research participants, clinicians, bioethics scholars, experts in human research protections, and government representatives. Discussion was directed by experienced facilitators and informed by empirical data collected in a national survey of IRB chairs and in-depth interviews with research participants in studies where genotype-driven recontact occurred. A high degree of consensus was attained on the resulting seven recommendations, which cover informed consent disclosures and choices, the process for how and by whom participants are recontacted, the disclosure of individual genetic research results, and the importance of tailoring approaches based on specific contextual factors. These recommendations are intended to represent a balanced approach-protecting research participants, yet avoiding overly restrictive policies that hinder advancement on important scientific questions.

Scientists' Views on Scientific Self-Governance for Human Genome Editing Research.

As research on human gene editing has grown, a variety of prominent international organizations are considering how best to govern such research. But what role do scientists engaged in genome editing think they should have in developing research governance? In this study, we present results from a survey of 212 U.S.-based scientists regarding views on human genome editing governance. Most did not believe that scientists should be allowed to self-govern human genome editing research. Open-ended responses revealed four main reasons: conflicts of interest, the inevitability of rare "bad apples," historical evidence to the contrary, and the limitations of scientific expertise. Analyses of open-ended responses also revealed scientists' views on how human gene editing research should be governed. These views emphasize interdisciplinary professional and public input. The study results illustrate a noteworthy shift in the scientific community's traditional vision of professional autonomy and can inform ongoing efforts to develop research governance approaches.

"That's a good question": university researchers' views on ownership and retention of human genetic specimens.

PURPOSE: To explore the views of university-based investigators conducting genetic research with human specimens regarding ownership and retention of specimens, and knowledge of related institutional review board and university policies. METHODS: Data were collected in three phases: a qualitative pilot study of 14 investigators; a web-based survey taken by 80 investigators; and follow-up, in-depth interviews with 12 survey respondents. RESULTS: Investigators named a variety of single or multiple owners of human specimens and often expressed confusion regarding specimen ownership. Most associated ownership with rights to control, and responsibilities to maintain, specimens. Investigators viewed specimens as "precious" resources whose value could be increased through long-term or infinite retention, particularly in light of anticipated technological advances in genome science. Their views on ownership and retention were shaped by perceptions of institutional review board policies as immortalized in subject informed consent documents, rather than knowledge of actual policies. CONCLUSION: Long-term retention of human specimens makes confusion about ownership particularly problematic. Given findings that investigators' views on ownership and retention are largely guided by their perception of university policies, the need for clear, consistent policies at the institution level is urgent.

Is Real-Time ELSI Realistic?

Background: A growing literature has raised-skeptically-the question of whether cutting-edge scientific research can identify and address broader ethical and policy considerations in real time. In genomics, the question is: Can ELSI contribute to genomics in real time, or will it be relegated to its historical role of after-the-fact outsider critique? We address this question against the background of a genomic screening project where we participated as embedded, real-time ELSI researchers and observers, from its initial design through its conclusion.Methods: As part of the ELSI study design, the project included an ongoing reflexive ethnography in which the authors studied the process of its design and implementation. The authors were true participant observers, serving as members of various task-oriented groups while recording meetings and other events for ongoing qualitative analysis. We also conducted and analyzed interviews of multiple participants at the conclusion of the project.Results: Our real-time ELSI initiative had a mixed record of successes and challenges. If we define success as ELSI researchers having had an opportunity to participate fully in the project and to make the ELSI perspective heard, then our assessment is largely positive. If, however, we define successes as instances where real-time ELSI contributions changed the direction of the genomic or public health aspects of the GeneScreen project or, after careful deliberation, confirmed the appropriateness of the status quo, then we can identify only a few examples. While we had a seat at the table, we were, for the most part, tolerated guests.Conclusions: We conclude that there are significant barriers to real-time ELSI influence. The difficulty does not reside in any intended exclusion of an ELSI perspective, but in factors endemic to genomic research, including knowledge disparities, epistemological biases, and the pressures of time and money.

A New Governance Approach to Regulating Human Genome Editing.

For years, genomic medicine-medicine based on the growing understanding of the genetic contribution to many diseases and conditions-has been hailed as the future of medical treatment, but it has thus far had limited effect on day-to-day medical practice. The ultimate goal of genomic medicine has always been the ability not just to identify dangerous gene mutations, but to fix them. Now CRISPR and related genome-editing technologies may have the potential to provide a safe and effective way to repair dangerous mutations. In the wake of ethically dubious experiments with human embryos in China, the international governance of human genome editing is emerging as an urgent topic for scientists, regulators, and the public. Efforts to develop a governance model are underway at national and international levels. These efforts are the subject of multiple initiatives by national and international health and science organizations and are topics of discussion at scientific conferences, summits, and meetings. This Article reports on the Authors' multi-year, interdisciplinary project to identify and investigate the practical, ethical, and policy considerations that are emerging as the greatest concerns about human genome editing, and ultimately to develop policy options. The project involves monitoring the discussions of groups, both government-sponsored and private, that are considering how genome editing should be governed; observing conferences where the topic is discussed; analyzing emerging policy reports by national and international bodies; and interviewing a wide range of stakeholders, including scientists, ethicists, and those who make and comment on public policy. The Article identifies several stakeholder concerns that are especially prominent in the research to date and begins to explore the implications of these concerns for alternative models of governance. There are current indications that, for practical purposes, a focus on "soft," hybrid forms of governance based on networks of multiple public and private stakeholders may turn out to be the most promising course to pursue. The "new governance" paradigm developed in the corporate and financial sectors offers a useful model for understanding the dynamics of this approach.

A place for genetic uncertainty: parents valuing an unknown in the meaning of disease.

Klinefelter, Turner, and fragile X syndromes are conditions defined by a genetic or chromosomal variant. The timing of diagnosis, tests employed, specialists involved, symptoms evident, and prognoses available vary considerably within and across these syndromes, but all three share in common a diagnosis verified through a molecular or cytogenetic test. The genetic or chromosomal variant identified designates a syndrome, even when symptoms associated with the particular syndrome are absent. This article analyzes interviews conducted with parents and grandparents of children with these syndromes from across the USA to explore how they interpret a confirmed genetic diagnosis that is associated with a range of possible symptoms that may never be exhibited. Parents' responses indicate that they see the genetic aspects of the syndrome as stable, permanent, and authoritative. But they allow, and even embrace, uncertainty about the condition by focusing on variation between diagnosed siblings, the individuality of their diagnosed child, his or her accomplishments, and other positive aspects that go beyond the genetic diagnosis. Some families counter the genetic diagnosis by arguing that in the absence of symptoms, the syndrome does not exist. They use their own expertise to question the perceived certainty of the genetic diagnosis and to employ the diagnosis strategically. These multiple and often conflicting evaluations of the diagnostic label reveal the rich ways families make meaning of the authority attributed to genetic diagnosis.