Ethical, Legal, and Social Issues (ELSI) in Clinical Genetics Research.

ELSI (Ethical, Legal, and Social Issues) is a widely used acronym in the bioethics literature that encompasses a broad range of research examining the various impacts of science and technology on society. In Canada, GE3LS (Genetics, Ethical, Economic, Environmental, Legal, Social issues) is the term used to describe ELSI studies in the context of genetics and genomics research. It is intentionally more expansive in that GE3LS explicitly brings economic and environmental issues under its purview. ELSI/GE3LS research is increasingly relevant in recent years as there has been a greater emphasis on "translational research" that moves genomic discoveries from the bench to the clinic. The purpose of this chapter is to outline a range of ELSI-related work that might be conducted as part of a large scale genetics or genomics research project, and to provide some practical insights on how a scientific research team might incorporate a strong and effective ELSI program within its broader research mandate. We begin by describing the historical context of ELSI research and the development of GE3LS research in the Canadian context. We then illustrate how some ELSI research might unfold by outlining a variety of GE3LS research questions or content domains and the methodologies that might be employed in studying them. We conclude with some practical suggestions about how to build an effective ELSI/GE3LS team and focus within a broader scientific research program.

Perceptions of best practices for return of results in an international survey of psychiatric genetics researchers.

Many research sponsors and genetic researchers agree that some medically relevant genetic findings should be offered to participants. The scarcity of research specific to returning genetic results related to psychiatric disorders hinders the ability to develop ethically justified and empirically informed guidelines for responsible return of results for these conditions. We surveyed 407 psychiatric genetics researchers from 39 countries to examine their perceptions of challenges to returning individual results and views about best practices for the process of offering and returning results. Most researchers believed that disclosure of results should be delayed if a patient-participant is experiencing significant psychiatric symptoms. Respondents felt that there is little research on the impact of returning results to participants with psychiatric disorders and agreed that return of psychiatric genetics results to patient-participants may lead to discrimination by insurance companies or other third parties. Almost half of researchers believed results should be returned through a participant's treating psychiatrist, but many felt that clinicians lack knowledge about how to manage genetic research results. Most researchers thought results should be disclosed by genetic counselors or medical geneticists and in person; however, almost half also supported disclosure via telemedicine. This is the first global survey to examine the perspectives of researchers with experience working with this patient population and with these conditions. Their perspectives can help inform the development of much-needed guidelines to promote responsible return of results related to psychiatric conditions to patients with psychiatric disorders.

Old Challenges or New Issues? Genetic Health Professionals' Experiences Obtaining Informed Consent in Diagnostic Genomic Sequencing.

BACKGROUND: While integrating genomic sequencing into clinical care carries clear medical benefits, it also raises difficult ethical questions. Compared to traditional sequencing technologies, genomic sequencing and analysis is more likely to identify unsolicited findings (UF) and variants that cannot be classified as benign or disease-causing (variants of uncertain significance; VUS). UF and VUS pose new challenges for genetic health professionals (GHPs) who are obtaining informed consent for genomic sequencing from patients. METHODS: We conducted semi-structured interviews with 31 GHPs across Europe, Australia and Canada to identify some of these challenges. RESULTS: Our results show that GHPs find it difficult to prepare patients to receive results because a vast amount of information is required to fully inform patients about VUS and UF. GHPs also struggle to engage patients - many of whom may be focused on ending their 'diagnostic odyssey' - in the informed consent process in a meaningful way. Thus, some questioned how 'informed' patients actually are when they agree to undergo clinical genomic sequencing. CONCLUSIONS: These findings suggest a tension remains between sufficient information provision at the risk of overwhelming the patient and imparting less information at the risk of uninformed decision-making. We suggest that a shift away from 'fully informed consent' toward an approach aimed at realizing, as far as possible, the underlying goals that informed consent is meant to promote.

Ethical, Legal, and Social Issues (ELSI) of Responsible Data Sharing Involving Children in Genomics: A Systematic Literature Review of Reasons.

BACKGROUND: Progress in precision medicine relies on the access to, use of, and exchange of genomic and associated clinical data, including from children. The ethical, legal, and social issues (ELSI) of such data access, use, and exchange may be accentuated in the pediatric context due in part to the highly sensitive nature of genomic data, children's consent-related vulnerabilities, and uncertain risks of reidentification. Systematic analyses of the ELSI and scientific reasons for why and how genomic data may be shared responsibly are, however, limited. Methods: We conducted a modified systematic review of reasons according to Sofaer and Strech to examine the ELSI and scientific reasons for "responsible" sharing of children's genomic and associated clinical data. Empirical articles, commentaries, and data-sharing policies indexed in Medline, Scopus, Web of Science, and BIOSIS were included in the analysis if they discussed ELSI and were published between 2003 and 2017 in English. Results: One hundred and fifty-one records met our inclusion criteria. We identified 11 unique reasons and 8 subreasons for why children's genomic data should or should not be shared. Enhancing the prospect of direct and indirect benefits and maximizing the utility of children's data were top reasons why data should be shared. Inadequate data privacy protection was the leading reason why it should not. We furthermore identified 8 reasons and 30 subreasons that support conditional data sharing, in which recontact for the continued use of children's data once they reach the age of majority was the most frequently endorsed condition. Conclusions: The complete list of ELSI reasons and responsible conditions provides an evidentiary basis upon which institutions can develop data-sharing policies. Institutions should encourage the sharing of children's data to advance genomic research, while heeding special reconsent and data protection mechanisms that may help mitigate uncertain longitudinal risks for children and families.

The Skeleton in the Closet: Faults and Strengths of Public Versus Private Genetic Biobanks.

Direct-to-consumer (DTC) genetic testing has been a major ethical controversy related to clinical utility, the availability of pre- and post-genetic counseling, privacy concerns, and the risk of discrimination and stigmatization. The development of direct-to-consumer genetic testing cannot leave aside some considerations on how the samples are managed once the analyses have been completed and the customer has received a response. The possibility that these samples are maintained by the structure for future research uses, explains the definition, which has been proposed in the literature, of these structures such as private genetic biobanks. The most relevant aspects that may impact ethical aspects, allowing a comparison between the public and private dimensions of genetic biobanks, are mainly transparency and participant/donor trust. The article aims to analyze the main line of ethical debate related to the mentioned practices and to explore whether market-based and consumer rights regarding DTC genetic testing can be counterbalanced by healthcare system developments based on policies that encourage the donation of samples in the context of public biobanks. A platform for dialogue, both technical-scientific and ethical, is indispensable between the public sector, the private sector and citizens to truly maximize both transparency and public trust in both contexts.

Factors Influencing Participation in Biospecimen Research among Parents of Youth with Mental Health Conditions.

INTRODUCTION: Biospecimens are tools that have the potential to improve early identification and treatment for autism spectrum disorders (ASD) and bipolar disorders (BPD). Unfortunately, most biobanks lack racial/ethnic diversity. One challenge to including a diverse sample of youth is recruiting and engaging families. OBJECTIVE: We sought to better understand facilitators and barriers to participation in biospecimen research among a diverse group of parents of youth with ASD and BPD. METHODS: The current study involved 3 Mental Health Research Network sites. At each site, parents participated in an interview that explored attitudes and beliefs about genetic research. Interviews were audio-recorded, and audio files were transcribed and coded using content analysis. RESULTS: A total of 58 interviews were conducted. Four challenges emerged: (1) contacting and engaging potential research participants, (2) motivating potential participants to read recruitment and consent materials, (3) motivating participation in research, in general, and (4) motivating participation in research involving biospecimen donation, specifically. CONCLUSIONS: Participants were eager to participate as long as the research process involved trust, clarity, and flexibility. Future research involving youth with mental health conditions would benefit from implementing multimodal strategies for recruitment and data collection and sharing knowledge gained by the research with study participants.

Return of Research-Related Genetic Test Results and Genetic Discrimination Concerns: Facilitators and Barriers of Genetic Research Participation in Diverse Groups.

BACKGROUND: Most genetics studies lack the diversity necessary to ensure that all groups benefit from genetic research. OBJECTIVES: To explore facilitators and barriers to genetic research participation. METHODS: We conducted a survey on genetics in research and healthcare from November 15, 2017 to February 28, 2018 among adult Kaiser Permanente (KP) members who had been invited to participate in the KP biobank (KP Research Bank). We used logistic regression to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) comparing the willingness to participate in genetic research under different return of results scenarios and genetic discrimination concerns between groups, according to their demographic characteristics. RESULTS: A total of 57,331 KP members were invited to participate, and 10,369 completed the survey (18% response rate). Respondents were 65% female, 44% non-Hispanic White (NH White), 22% Asian/Native Hawaiian or other Pacific Islander (Asian/PI), 19% non-Hispanic Black (NH Black), and 16% Hispanic. Respondents willing to participate in genetic research ranged from 22% with no results returned to 87% if health-related genetic results were returned. We also found variation by race/ethnicity; when no results were to be returned, Asian/PIs, Hispanics, and NH Blacks were less likely to want to participate than NH Whites (p < 0.05). However, when results were returned, disparities in the willingness to participate disappeared for NH Blacks and Hispanics. Genetic discrimination concerns were more prevalent in Asian/PIs, Hispanics, and NH Blacks than in NH Whites (p < 0.05). CONCLUSIONS: Policies that prohibit the return of results and do not address genetic discrimination concerns may contribute to a greater underrepresentation of diverse groups in genetic research.

Race and Genetics: Somber History, Troubled Present.

Following the completion of the Human Genome Project (HGP) in 2003, advances in DNA sequencing technologies further popularized the field of genomics and brought its social ramifications to the fore. Scholars across disciplines recently voiced serious concerns about the re-emergence of genomic research that might be used to justify racism. In this piece, I trace the history of attempts to biologize the concept of race and its diffused presence in today's genomic research. I then include a brief analysis inspired by concepts from the field of Science and Technology Studies (STS) to suggest selected ways to produce better scientific knowledge. The text highlights historic landmarks of interest to science practitioners curious about the ways science of the past co-shapes science of the present. I then argue that science has never been isolated from the socio-political climate it is produced in; instead, it has been morphed by its surroundings and historically used as a potent tool to justify systemic oppression.

Rights, interests and expectations: Indigenous perspectives on unrestricted access to genomic data.

Addressing Indigenous rights and interests in genetic resources has become increasingly challenging in an open science environment that promotes unrestricted access to genomic data. Although Indigenous experiences with genetic research have been shaped by a series of negative interactions, there is increasing recognition that equitable benefits can only be realized through greater participation of Indigenous communities. Issues of trust, accountability and equity underpin Indigenous critiques of genetic research and the sharing of genomic data. This Perspectives article highlights identified issues for Indigenous communities around the sharing of genomic data and suggests principles and actions that genomic researchers can adopt to recognize community rights and interests in data.

An Alaska Native community's views on genetic research, testing, and return of results: Results from a public deliberation.

As genetic testing technology advances, genetic testing will move into standard practice in the primary care setting. Genetic research, testing, and return of results are complex topics that require input from Alaska Native and American Indian (ANAI) communities as policies are developed for implementation. This study employed a day and half long public deliberation with ANAI primary care patients to elicit value-laden views of genetic research, testing, and return of results. Participants emphasized the need for a balance between the potential for genetics research, testing, and return of results to empower individuals and improve health with the potential to expose individuals and communities to privacy breaches, discrimination, and emotional harms. Public deliberation was well received by this group of participants and elicited rich discussion on the complex topic of genetic research, testing, and return of results.

Why genomics researchers are sometimes morally required to hunt for secondary findings.

BACKGROUND: Genomic research can reveal 'unsolicited' or 'incidental' findings that are of potential health or reproductive significance to participants. It is widely thought that researchers have a moral obligation, grounded in the duty of easy rescue, to return certain kinds of unsolicited findings to research participants. It is less widely thought that researchers have a moral obligation to actively look for health-related findings (for example, by conducting additional analyses to search for findings outside the scope of the research question). MAIN TEXT: This paper examines whether there is a moral obligation, grounded in the duty of easy rescue, to actively hunt for genomic secondary findings. We begin by showing how the duty to disclose individual research findings can be grounded in the duty of easy rescue. Next, we describe a parallel moral duty, also grounded in the duty of easy rescue, to actively hunt for such information. We then consider six possible objections to our argument, each of which we find unsuccessful. Some of these objections provide reason to limit the scope of the duty to look for secondary findings, but none provide reason to reject this duty outright. CONCLUSIONS: We argue that under a certain range of circumstances, researchers are morally required to hunt for these kinds of secondary findings. Although these circumstances may not currently obtain, genomic researchers will likely acquire an obligation to hunt for secondary findings as the field of genomics continues to evolve.

Do patients and research subjects have a right to receive their genomic raw data? An ethical and legal analysis.

BACKGROUND: As Next Generation Sequencing technologies are increasingly implemented in biomedical research and (translational) care, the number of study participants and patients who ask for release of their genomic raw data is set to increase. This raises the question whether research participants and patients have a legal and moral right to receive their genomic raw data and, if so, how this right should be implemented into practice. METHODS: In a first step we clarify some central concepts such as "raw data"; in a second step we sketch the international legal framework. The third step provides an extensive ethical analysis which comprehends two parts: an evaluation of whether there is a prima facie moral right to receive one's raw data, and a contextualization and discussion of the right in light of potentially conflicting interests and rights of the data subject herself and third parties; in a last fourth step we emphasize the main practical consequences of the ethical analyses and propose recommendations for the release of raw data. RESULTS: In several legislations like the new European General Data Protection Regulation, patients do in principle have the right to receive their raw data. However, the procedural implementation of this right and whether it involves genetic counselling is at the discretion of the Member States. Even more questions remain with respect to the research context. The ethical analysis suggests that patients and research subjects have a moral right to receive their genomic raw data and addresses aspects which are also of relevance for the legal discussion such as the costs of release of raw data and its impact on academic freedom. CONCLUSION: Taking into account the specific nature and implications of genomic raw data and the contexts of research and health care, several concerns and potentially conflicting interests of the data subjects themselves and involved researchers, physicians, biomedical institutions and relatives arise. Instead of using them to argue in favor of restrictions of the data subjects' legal and moral right to genomic raw data, the concerns should be addressed through provision of information and other measures. To this end, we propose relevant recommendations.

Psychiatric genomics researchers' perspectives on best practices for returning results to individual participants.

PURPOSE: Large-scale array-based and sequencing studies have advanced our understanding of the genetic architecture of psychiatric disorders, but also increased the potential to generate an exponentially larger amount of clinically relevant findings. As genomic testing becomes more widespread in psychiatry research, urgency grows to establish best practices for offering return of results (RoR) to individuals at risk or diagnosed with a psychiatric disorder. METHODS: We interviewed an international sample (n = 39) of psychiatric genetics researchers to examine conceptualizations of "best practices" for RoR to individual research participants. RESULTS: While the vast majority of researchers do not offer RoR, most believed medically actionable findings (85%) and clinically valid but non-medically actionable findings (54%) should be offered. Researchers identified three main areas for improvement: interfacing with individual participants; interdisciplinary training, guidance, and integration; and quality planning and resource allocation for returning results. CONCLUSION: There are significant gaps between researchers' visions for "best" versus "actual" RoR practices. While researchers call for participant-centered practices, including consent practices that consider any special needs of participants with psychiatric disorders, return of individually meaningful results, and effective follow-up and provisions for treatment, the current reality is that consent and RoR practices lack standardized and evidence-based norms.

Psychological factors that determine people's willingness-to-share genetic data for research.

Of all the information that we share, health and genetic data might be among the most valuable for researchers. As data are handled as particularly sensitive information, a number of pressing issues regarding people's preferences and privacy concerns are raised. The goal of the present study was to contribute to an understanding of people's reported willingness-to-share genetic data for science (WTS). For this, predictive psychological factors (eg, risk and benefit perceptions, trust, knowledge) were investigated in an online survey (N = 416). Overall, participants seemed willing to provide their genetic data for research. Participants who perceived more benefits associated with data sharing were particularly willing to share their data for research (ß = .29), while risk perceptions were less influential (ß = -.14). As participants with higher knowledge of the potential uses of genetic data for research perceived more benefits (ß = .20), WTS can likely be improved by providing people with information regarding the usefulness of genetic data for research. In addition to knowledge and perceptions, trust in data recipients increased people's willingness-to-share directly (ß = .24). Especially in the sensitive area of genetic data, future research should strive to understand people's shifting perceptions and preferences.

Why parents consent to their children's participation in genetic research: A study of parental decision making.

Parents need to be asked to provide informed consent on behalf of their child for participation in genetic research. Decision making for such parents is difficult because ethical challenges in paediatric genetic research studies are different from similar adult studies. This paper focuses on interviews conducted with parents who were asked to consent to their children's participation (or not) in a genetic research study of intellectual disability and/or autism.

Edición genómica y libertad de investigación: ¿nuevos retos para viejos derechos? / Genome editing and scientific freedom: new challenges for old rights?

El sistema CRISPR-Cas ha permitido editar el genoma de células y organismos vivos de forma sencilla y precisa. Pese a su extendido uso en diversas áreas de investigación en Biología, incluida la Biomedicina, existen problemas de seguridad que han de ser analizados antes de que el llamado 'bisturí molecular' llegue a la práctica clínica. Sin embargo, en noviembre de 2018, un científico chino aseguró haber creado las dos primeras bebés editadas genéticamente para conferirles resistencia al VIH. El experimento abre el debate sobre la libertad de investigación, un derecho fundamental que no solo ha permitido importantes avances en Genética, sino que también podría afectar otros derechos y libertades. El presente artículo aborda los desafíos en la relación entre la edición genómica y la libertad de investigación

The CRISPR-Cas system has enabled scientists to easily and precisely edit the genome in cells and living organisms. Despite its widespread use in many biological research areas, including Biomedicine, there are still important safety issues that need to be addressed before translating the so-called 'molecular scalpel' to clinical practice. However, in November 2018, a Chinese scientist claimed to had created the first genetically edited babies to make them more resistant to HIV. The experiment opens the debate about scientific freedom, a fundamental right that not only has allowed important advances in Genetics, but could also affect other rights and liberties. The present article discusses the challenges ahead the relationship between genome editing and scientific freedom

Reprogenetics, reproductive risks and cultural awareness: what may we learn from Israeli and Croatian medical students?

BACKGROUND: Past studies emphasized the possible cultural influence on attitudes regarding reprogenetics and reproductive risks among medical students who are taken to be "future physicians." These studies were crafted in order to enhance the knowledge and expand the boundaries of cultural competence. Yet such studies were focused on MS from relatively marginalized cultures, namely either from non-Western developing countries or minority groups in developed countries. The current study sheds light on possible cultural influences of the dominant culture on medical students in two developed countries, potentially with different dominant cultures regarding reprogenetics and reproductive risks: Israel and Croatia. METHODS: Quantitative-statistical analyses were employed, based on anonymous questionnaires completed by 150 first year medical students in Israel and Croatia. The questionnaires pertained to the knowledge and attitudes regarding genetics, reproduction and reproductive risks. These questionnaires were completed before the students were engaged in learning about these topics as part of the curriculum in their medical school. RESULTS: Substantial differences were revealed between the two groups of medical students. Israeli medical students were less tolerant regarding reproductive risks and more knowledgeable about genetics and reproductive risks than Croatian medical students. For example, while nearly all Israeli medical students (96%) disagreed with the idea that "Screening for reproductive risks in prospective parents is wrong," less than 40% of their Croatian counterparts shared a similar stance. Similarly, all (100%) Israeli medical students correctly observed that "A carrier of a recessive genetic disease actually has the disease" was wrong, as opposed to only 82% of Croatian students. CONCLUSIONS: By linking applicable theoretical literature to these findings, we suggest that they may reflect the hidden influence of the dominant culture in each country, disguised as part of the "culture of medicine." Acknowledging and learning about such influence of the dominant culture, may be an important addition to the training of medical students in cultural competence, and specifically their cultural awareness. Such an acknowledgement may also pave the road to drawing the attention of existing physicians regarding a less known yet an important aspect of their cultural competence, insofar as the cultural awareness component is concerned.