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.

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."

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.

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.

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.

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.

Membership recruitment and training in health care ethics committees: Results from a national pilot survey.

This pilot study reports on a survey regarding recruitment, appointment, and training of members for health care ethics committees (HCECs). BACKGROUND: Past studies have examined HCECs, but have focused on the roles of the committees and the broad makeup of membership. Thus, our study fills an important knowledge gap in trends of membership recruitment and appointment processes employed by HCECs to comprise their membership. METHODS: We posted our survey on several bioethics listservs between June and August 2015. Of the 103 respondents that started the survey, 59 were eligible for inclusion based on our criteria. We analyzed survey results descriptively and qualitatively. RESULTS: Overall we found no unifying standards of recruitment or appointment across the 59 respondents. Additionally, while responding committees varied in the professional backgrounds and attributes they valued in potential members, we found that most respondents valued traits of the applicants over specific knowledge or skills. CONCLUSIONS: This study provides a first look into how HCECs recruit members. Future research is needed to better understand the complexities of the issues discovered during this study, given that the HCEC members appointed are the individuals who fulfill committee obligations.

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.

Which Results to Return: Subjective Judgments in Selecting Medically Actionable Genes.

BACKGROUND: Advances in genomics have led to calls for returning information about medically actionable genes (MAGs) to patients, research subjects, biobank participants, and through screening programs, the general adult population. Which MAGs are returned affects the harms and benefits of every genetic testing endeavor. Despite published recommendations of selection criteria for MAGs to return, scant data exist regarding how decision makers actually apply such criteria. METHODS: The process and criteria used by researchers when selecting MAGs for a preventive genomic sequencing program targeting the general adult population were examined. The authors observed and audio-recorded the gene selection meetings, and analyzed meeting transcripts, gene scoring sheets, and meeting handouts. RESULTS: To select MAGs, the committee imported, from a preexisting project, "a semiquantitative metric" that scores genes on five criteria. Numerous subjective judgments and conceptual challenges in defining and applying the five criteria complicated the selection process. Criteria-related challenges also included the limited evidence available about facts fundamental to the scoring decisions and the emergence and application of criteria that were not part of the original metric. CONCLUSIONS: When identifying MAGs appropriate for screening and return, decision makers must expect and prepare to address such issues as the inevitability of subjective judgments, limited evidence about fundamental decision-making elements, the conceptual complexity of defining criteria, and the emergence of unplanned criteria during the gene selection process.

"Forward-Thinking" in U.S. Biobanking.

AIMS: Do biobanks enact policies and plans that allow them to anticipate and respond to potential challenges? If a biobank has one such policy or plan, is it likely to have more? Using survey data from 456 U.S. biobanks, we assess four possible indicators of such "forward-thinking." METHODS: We present response frequencies and cross-tabulations regarding policies for return of results and ownership of specimens, and for having a formal business plan and a plan for what happens to specimens if the biobank closes. We analyze the relationships among these indicators, using chi-square for tests of statistical significance. RESULTS: Policies-Sixty-two percent of biobanks have a policy about returning individual research results; 70% have a policy designating ownership of specimens and/or technology. Having these two policies is significantly related (p < 0.001). Plans-34% of biobanks have a formal business plan; 26% have a written plan for what will happen to the specimens if the biobank closes. Having these two plans is significantly related (p < 0.001). Relationships among indicators-only 7% of biobanks are forward-thinking across all four indicators; 12% are forward-thinking across none. DISCUSSION: The two policies we examined tend to occur together, as do the two plans. These policies and plans seem to tap different aspects of accountability and responsiveness. Specifically, the policies reflect issues most commonly raised in the ethical and legal literature on biobanking, while the plans are indicators of sustainability, a separate area of concern in biobanking.

An Evaluation of the Middle East Research Training Initiative Tool in Assessing Effective Functioning of Research Ethics Committees.

The effective functioning of a research ethics committee (REC) can be evaluated using self-assessment tools. The Middle East Research Ethics Training Initiative (MERETI) tool can be used by one member, typically the Chair, to score an REC. The consistency of these scores across several members of an REC has never been evaluated. This study examined whether results would be consistent irrespective of who conducts the assessment. One REC's effective functioning was assessed by several members ( n = 13). The Chair's scores were compared with scores of other members in relation to their duration of REC membership, research ethics training, gender, and employer's institutional affiliation to the REC. The Chair's overall score was higher than the other members' scores by 11%. No significant differences in scores were obtained in relation to duration of REC membership ( p = .72), interval since last research ethics training ( p = .94), and gender ( p = .27). The MERETI tool is thus consistent irrespective of who performs the assessment.

Automatic Placement of Genomic Research Results in Medical Records: Do Researchers Have a Duty? Should Participants Have a Choice?

In genomics research, it is becoming common practice to return individualized primary and incidental findings to participants and several ongoing major studies have begun to automatically transfer these results to a participant's clinical medical record. This paper explores who should decide whether to place genomic research findings into a clinical medical record. Should participants make this decision, or does a researcher's duty to place this information in a medical record override the participant's autonomy? We argue that there are no clear ethical, legal, professional, or regulatory duties that mandate placement without the consent of the participant. We conclude that informing participants of results, together with a clear explanation, relevant recommendations and referral sources, and the option to consent to placement in the medical records will best discharge researchers' ethical and legal duties towards participants.