Addressing underrepresentation in genomics research through community engagement.

The vision of the American Society of Human Genetics (ASHG) is that people everywhere will realize the benefits of human genetics and genomics. Implicit in that vision is the importance of ensuring that the benefits of human genetics and genomics research are realized in ways that minimize harms and maximize benefits, a goal that can only be achieved through focused efforts to address health inequities and increase the representation of underrepresented communities in genetics and genomics research. This guidance is intended to advance community engagement as an approach that can be used across the research lifecycle. Community engagement uniquely offers researchers in human genetics and genomics an opportunity to pursue that vision successfully, including by addressing underrepresentation in genomics research.

Governing new technologies that stop biological time: Preparing for prolonged biopreservation of human organs in transplantation.

Time limits on organ viability from retrieval to implantation shape the US system for human organ transplantation. Preclinical research has demonstrated that emerging biopreservation technologies can prolong organ viability, perhaps indefinitely. These technologies could transform transplantation into a scheduled procedure without geographic or time constraints, permitting organ assessment and potential preconditioning of the recipients. However, the safety and efficacy of advanced biopreservation with prolonged storage of vascularized organs followed by reanimation will require new regulatory oversight, as clinicians and transplant centers are not trained in the engineering techniques involved or equipped to assess the manipulated organs. Although the Food and Drug Administration is best situated to provide that process oversight, the agency has until now declined to oversee organ quality and has excluded vascularized organs from the oversight framework of human cells, tissues, and cellular-based and tissue-based products. Integration of advanced biopreservation technologies will require new facilities for organ preservation, storage, and reanimation plus ethical guidance on immediate organ use versus preservation, national allocation, and governance of centralized organ banks. Realization of the long-term benefit of advanced biopreservation requires anticipation of the necessary legal and ethical oversight tools and that process should begin now.

iPS cells: mapping the policy issues.

Given the explosion of research on induced pluripotent stem (iPS) cells, it is timely to consider the various ethical, legal, and social issues engaged by this fast-moving field. Here, we review issues associated with the procurement, basic research, and clinical translation of iPS cells.

Human Germline Genome Editing.

With CRISPR/Cas9 and other genome-editing technologies, successful somatic and germline genome editing are becoming feasible. To respond, an American Society of Human Genetics (ASHG) workgroup developed this position statement, which was approved by the ASHG Board in March 2017. The workgroup included representatives from the UK Association of Genetic Nurses and Counsellors, Canadian Association of Genetic Counsellors, International Genetic Epidemiology Society, and US National Society of Genetic Counselors. These groups, as well as the American Society for Reproductive Medicine, Asia Pacific Society of Human Genetics, British Society for Genetic Medicine, Human Genetics Society of Australasia, Professional Society of Genetic Counselors in Asia, and Southern African Society for Human Genetics, endorsed the final statement. The statement includes the following positions. (1) At this time, given the nature and number of unanswered scientific, ethical, and policy questions, it is inappropriate to perform germline gene editing that culminates in human pregnancy. (2) Currently, there is no reason to prohibit in vitro germline genome editing on human embryos and gametes, with appropriate oversight and consent from donors, to facilitate research on the possible future clinical applications of gene editing. There should be no prohibition on making public funds available to support this research. (3) Future clinical application of human germline genome editing should not proceed unless, at a minimum, there is (a) a compelling medical rationale, (b) an evidence base that supports its clinical use, (c) an ethical justification, and (d) a transparent public process to solicit and incorporate stakeholder input.

Including all voices in international data-sharing governance.

BACKGROUND: Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. MAIN TEXT: The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decision-making. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. CONCLUSIONS: We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable perspectives into the decision-making around international data sharing.

Model consent clauses for rare disease research.

BACKGROUND: Rare Disease research has seen tremendous advancements over the last decades, with the development of new technologies, various global collaborative efforts and improved data sharing. To maximize the impact of and to further build on these developments, there is a need for model consent clauses for rare diseases research, in order to improve data interoperability, to meet the informational needs of participants, and to ensure proper ethical and legal use of data sources and participants' overall protection. METHODS: A global Task Force was set up to develop model consent clauses specific to rare diseases research, that are comprehensive, harmonized, readily accessible, and internationally applicable, facilitating the recruitment and consent of rare disease research participants around the world. Existing consent forms and notices of consent were analyzed and classified under different consent themes, which were used as background to develop the model consent clauses. RESULTS: The IRDiRC-GA4GH MCC Task Force met in September 2018, to discuss and design model consent clauses. Based on analyzed consent forms, they listed generic core elements and designed the following rare disease research specific core elements; Rare Disease Research Introductory Clause, Familial Participation, Audio/Visual Imaging, Collecting, storing, sharing of rare disease data, Recontact for matching, Data Linkage, Return of Results to Family Members, Incapacity/Death, and Benefits. CONCLUSION: The model consent clauses presented in this article have been drafted to highlight consent elements that bear in mind the trends in rare disease research, while providing a tool to help foster harmonization and collaborative efforts.

Assessing opportunities and challenges for establishing a national program to distribute cord blood for research.

BACKGROUND: Research is needed to enhance cord blood (CB) transplantation outcomes and to develop new clinical applications. Based on quality criteria for transplantation, CB collected by public CB banks (CBBs) is often unsuitable for banking, but may still be valuable for research. Canadian researchers have described a need for a centralized program providing ethically sourced CB for research projects. To meet this need, Canadian Blood Services (CBS), in partnership with The Ottawa Hospital, launched the Cord Blood for Research Program (CBRP) in 2014. STUDY DESIGN AND METHODS: The CBRP developed processes for donor research consent and research project approval with oversight from CBS's CBB and appropriate research ethics boards. The CBRP distributes deidentified CB products to research projects across Canada. RESULTS: Since its inception, the CBRP has distributed more than 525 CB units to researchers, supporting 11 research projects. Of the mothers who donate their baby's CB, 77% have chosen to consent to its use for research if it is not bankable. The number of CB units currently available for research via the CBRP exceeds the requests from researchers. CONCLUSION: The CBRP reliably distributes quality CB products that do not qualify for banking to investigators across Canada in an ethical, legal, and transparent manner. This provides an opportunity for the public to directly support research, helps meet the need expressed by Canada's research community, and maximizes the donor's gift. More research is needed to clarify the factors influencing donor and researcher participation in the CBRP.

Developing Educational Resources to Advance Umbilical Cord Blood Banking and Research: A Canadian Perspective.

In 2013 Canadian Blood Services (CBS) launched the National Public Cord Blood Bank (NPCBB), a program to collect, process, test, and store cord blood units donated for use in transplantation. A key component of the creation of the NPCBB is the establishment of a program that enables cord blood not suitable for banking or transplantation to be used for biomedical research purposes. Along with the development of processes and policies to manage the NPCBB and the cord blood research program, CBS-in collaboration with researchers from the Stem Cell Network-have also developed educational tools to provide relevant information for target audiences to aid implementation and operation. We describe here one of these tools, the REB Primer on Research and Cord Blood Donation (the Primer), which highlights key ethical and legal considerations and identifies Canadian documents that are relevant to the use of cord blood in biomedical research. The Primer also introduces the NPCBB and describes the systems CBS is implementing to address ethical issues. The Primer is intended to assist research ethics boards in evaluating the ethical acceptability of research protocols, to facilitate harmonized decision-making by providing a common reference, and to highlight the role of research ethics boards in governance frameworks. With the Primer we hope to illustrate how the development of such educational tools can facilitate the ethical implementation and governance of programs related to stem cell research in Canada and abroad.

En 2013, la Société canadienne du sang (SCS) a lancé la Banque publique nationale de sang de cordon ombilical (BPNSCO) : un programme de prélèvement, de traitement, d'analyse et d'entreposage d'unités de sang de cordon ombilical ayant fait l'objet d'un don pour une utilisation dans le cadre de greffes. La mise sur pied d'un programme permettant l'utilisation, aux fins de la recherche biomédicale, du sang de cordon ombilical ne pouvant être mis en banque ni être utilisé pour des greffes constitue une composante clé de la création de la BPNSCO. Conjointement avec l'élaboration de processus et de politiques permettant la gestion de la BPNSCO et du programme de recherche sur le sang de cordon ombilical, la SCS (en collaboration avec les chercheurs du Réseau de cellules souches) ont également conçu des outils pédagogiques permettant l'offre de renseignements pertinents aux populations visées, de façon à faciliter la mise en œuvre et la gestion des activités. Nous décrivons ici l'un de ces outils : le REB Primer on Research and Cord Blood Donation (le « guide ¼). Ce « guide ¼ souligne les enjeux éthiques et légaux clés, et identifie les documents canadiens pertinents en ce qui concerne l'utilisation de sang de cordon ombilical aux fins de la recherche biomédicale. Ce « guide ¼ présente également la BPNSCO et décrit les systèmes qui sont mis en œuvre par la SCS pour répondre aux questions éthiques. Il a pour but d'aider les conseils d'éthique de la recherche à évaluer l'acceptabilité éthique des protocoles de recherche, de faciliter l'harmonisation des processus décisionnels en offrant un cadre de référence commun et de souligner le rôle des conseils d'éthique de la recherche dans les cadres de gouvernance. Grâce à ce « guide ¼, nous espérons illustrer la façon dont l'élaboration de tels outils pédagogiques peut faciliter la mise en œuvre et la gestion éthiques de programmes associés à la recherche sur les cellules souches au Canada et à l'étranger.

Policy recommendations for addressing privacy challenges associated with cell-based research and interventions.

BACKGROUND: The increased use of human biological material for cell-based research and clinical interventions poses risks to the privacy of patients and donors, including the possibility of re-identification of individuals from anonymized cell lines and associated genetic data. These risks will increase as technologies and databases used for re-identification become affordable and more sophisticated. Policies that require ongoing linkage of cell lines to donors' clinical information for research and regulatory purposes, and existing practices that limit research participants' ability to control what is done with their genetic data, amplify the privacy concerns. DISCUSSION: To date, the privacy issues associated with cell-based research and interventions have not received much attention in the academic and policymaking contexts. This paper, arising out of a multi-disciplinary workshop, aims to rectify this by outlining the issues, proposing novel governance strategies and policy recommendations, and identifying areas where further evidence is required to make sound policy decisions. The authors of this paper take the position that existing rules and norms can be reasonably extended to address privacy risks in this context without compromising emerging developments in the research environment, and that exceptions from such rules should be justified using a case-by-case approach. In developing new policies, the broader framework of regulations governing cell-based research and related areas must be taken into account, as well as the views of impacted groups, including scientists, research participants and the general public. SUMMARY: This paper outlines deliberations at a policy development workshop focusing on privacy challenges associated with cell-based research and interventions. The paper provides an overview of these challenges, followed by a discussion of key themes and recommendations that emerged from discussions at the workshop. The paper concludes that privacy risks associated with cell-based research and interventions should be addressed through evidence-based policy reforms that account for both well-established legal and ethical norms and current knowledge about actual or anticipated harms. The authors also call for research studies that identify and address gaps in understanding of privacy risks.

Dynamic governance: A new era for consent for stem cell research.

Governance infrastructures streamline scientific and ethical provenance verification of human pluripotent stem cell (SC) lines. Yet, scientific developments (e.g., SC-derived embryo models, organoids) challenge research governance approaches to stored biospecimens, questioning the validity of informed consent (IC) models. Likewise, e-health platforms are driving major transformations in data processing, prompting a reappraisal of IC. Given these developments, participatory research platforms are identified as effective tools to promote longitudinal engagement, interactive decision-making, and dynamic governance. Learning from European initiatives piloting dynamic IC for biobanking and SC research, this Perspective explores the benefits and challenges of implementing dynamic IC and governance for SC.

Modeling policy development: examining national governance of stem cell-based embryo models.

Researchers can now coax human pluripotent stem cells to imitate the structure and spontaneous self-organization of the developing human embryo. Although these stem cell-based embryo models present an advantageous alternative to embryo research, they also raise ethical and policy challenges. In 2021, the International Society for Stem Cell Research revised its Guidelines for Stem Cell Research and Clinical Translation, providing contemporaneous best practices for ethical conduct in the field. The Guidelines complement national governance frameworks; however, they also contain contentious and aspirational norms that might catalyze change in research practice and in the enactment of national policies. Using a sample of 11 research-intensive countries, the authors compare research policy frameworks against the International Society for Stem Cell Research Guidelines to showcase how developments in global and national policies might affect stem cell-based embryo model research governance and illustrate fertile areas for ethical reflection and policy development.

Following scientific advances, researchers can induce stem cells to model the development of the human embryo with increasing accuracy. The International Society for Stem Cell Research Guidelines for Stem Cell Research and Clinical Translation provide contemporary standards for research on so-called stem cell-based embryo models (SCB-EMs). However, because SCB-EMs are not mentioned in national policies and do not fit neatly into existing regulatory categories, it is unclear how countries intend to regulate them. In this article, the authors compare policy frameworks in 11 research-intensive countries to analyze how the influential Guidelines both complement and catalyze change in national policies. The Guidelines provide specific instructions for assessing and monitoring different kinds of SCB-EM research proposals, serving as a useful reference to bolster open-ended national policy requirements. However, in some areas the Guidelines appear to conflict with national policies governing stem cell and embryo research, reflecting divergent priorities and ethical assessments. Without policy review to address regulatory and ethical uncertainty, researchers may default to adherence to the Guidelines, a global standard that does not necessarily reflect local historic, legal and cultural influences. Evidence from France and Israel indicates that comprehensive legislative review is both useful and can proceed without eroding compromises designed to uphold plural beliefs regarding the moral status of the human embryo. As exemplified in countries such France and Israel, mandated legislative review processes are useful tools that can be deployed in manner that upholds pluralistic beliefs regarding the human embryo's moral status. They can serve as a pathway to re-engage the public and ensure diverse viewpoints are reflected in governance of SCB-EM research, ultimately facilitating public trust in science.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale. There were 5,769 HCHS/SOL participants who completed at least one survey question. Of the target population, 55.2% was aware of at least one type of genetic test. Awareness varied between HCHS/SOL enrollment sites and was higher among individuals who had higher educational attainment and had higher incomes. Only 3.3% of the target population reported receiving one or more of the tests described. HCHS/SOL individuals rated the usefulness as 8.4, on average, with lower scores observed among U.S.-born individuals compared to individuals born outside the United States, with differences by HCHS/SOL enrollment sites. In conclusion, while awareness of genetic testing among Hispanic and Latino individuals varies by location, education, and income, perceptions about its usefulness are high while experiences with testing are rare. Results identify groups and locations that may benefit from greater outreach about the capabilities of genetic testing and precision medicine.