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.

Randomized trial of a web-based survivor intervention on melanoma prevention behaviors of first-degree relatives.

OBJECTIVES: Melanoma can be prevented through reducing sun exposure and detected early by increasing examination of skin for lesions. First-degree relatives of melanoma cases have higher risk than the general population and, therefore, could be targets of behavioral interventions through families. We tested the effects of a family-based web delivered intervention to melanoma families on the melanoma risk reduction behaviors of first-degree relatives of melanoma cases. METHODS: A total of 313 families that included one first-degree relative were recruited to join this randomized trial. All intervention families received access to the Suntalk website developed to promote family communication and behavioral risk reduction among families of melanoma survivors. RESULTS: First degree relatives in the intervention arm significantly increased their yearly performance of both skin self examination and thorough provider examination from baseline to 12-month follow-up while the control FDRs decreased their yearly performance of both of those behaviors (p's = 0.006 and 0.005, respectively). Several sun protection behaviors increased significantly in FDRs in the intervention arm but not the control arm, including wearing a covering on the head (p = 0.005), staying in available shade (p = 0.008), and avoiding sun exposure during peak hours (p = 0.010). Some of these changes were mediated by perceptions of risk and other process variables. CONCLUSIONS: A web-based intervention can reduce risk of melanoma through changes in relevant behaviors among first-degree relatives of melanoma survivors. Future research should identify methods for making this type of intervention accessible to more families and for broadening the reach to other types of cancer families. PRACTICE IMPLICATIONS: This program can be provided to melanoma families to improve their sun protection and screening behaviors, at the point of diagnosis.

Navigating the research-clinical interface in genomic medicine: analysis from the CSER Consortium.

PurposeThe Clinical Sequencing Exploratory Research (CSER) Consortium encompasses nine National Institutes of Health-funded U-award projects investigating translation of genomic sequencing into clinical care. Previous literature has distinguished norms and rules governing research versus clinical care. This is the first study to explore how genomics investigators describe and navigate the research-clinical interface.MethodsA CSER working group developed a 22-item survey. All nine U-award projects participated. Descriptive data were tabulated and qualitative analysis of text responses identified themes and characterizations of the research-clinical interface.ResultsSurvey responses described how studies approached the research-clinical interface, including in consent practices, recording results, and using a research versus clinical laboratory. Responses revealed four characterizations of the interface: clear separation between research and clinical care, interdigitation of the two with steps to maintain separation, a dynamic interface, and merging of the two. All survey respondents utilized at least two different characterizations. Although research has traditionally been differentiated from clinical care, respondents pointed to factors blurring the distinction and strategies to differentiate the domains.ConclusionThese results illustrate the difficulty in applying the traditional bifurcation of research versus clinical care to translational models of clinical research, including in genomics. Our results suggest new directions for ethics and oversight.

Stakeholder engagement in policy development: challenges and opportunities for human genomics.

Along with rapid advances in human genomics, policies governing genomic data and clinical technologies have proliferated. Stakeholder engagement is widely lauded as an important methodology for improving clinical, scientific, and public health policy decision making. The purpose of this paper is to examine how stakeholder engagement is used to develop policies in genomics research and public health areas, as well as to identify future priorities for conducting evidence-based stakeholder engagements. We focus on exemplars in biobanking and newborn screening to illustrate a variety of current stakeholder engagement in policy-making efforts. Each setting provides an important context for examining the methods of obtaining and integrating informed stakeholder voices into the policy-making process. While many organizations have an interest in engaging stakeholders with regard to genomic policy issues, there is broad divergence with respect to the stakeholders involved, the purpose of engagements, when stakeholders are engaged during policy development, methods of engagement, and the outcomes reported. Stakeholder engagement in genomics policy development is still at a nascent stage. Several challenges of using stakeholder engagement as a tool for genomics policy development remain, and little evidence regarding how to best incorporate stakeholder feedback into policy-making processes is currently available.

Beliefs and Values About Gene Therapy and In-Utero Gene Editing in Patients with Hemophilia and Their Relatives.

AIM: Hemophilia is an inherited disease for which current treatment is noncurative. While gene therapy and gene editing are being researched, we do not know how the hemophilia community perceives them. Herein, we explore the beliefs and values regarding these new therapies in patients with hemophilia and their relatives. METHODS: This qualitative study used phone-based semi-structured interviews on 21 adult English-speaking patients with hemophilia A or B and their parents across the United States during March to July 2019. The study was advertised through different chapters of the Hemophilia Foundation. The interview guide included questions about participants' prior experience with hemophilia, and included two case scenarios about the use of gene therapy and in utero gene editing, after which participants were asked about their opinions, beliefs, and values on each scenario. We used a grounded theory approach and identified the main themes using an inductive process. RESULTS: We interviewed 21 participants-12 patients and 9 mothers. Most of them had or were related to a patient with severe disease. The main themes discussed were related to efficacy, safety and financial concerns and insurance coverage for both gene therapy and in utero gene editing. Patients and their parents had expected outcomes in terms of durability of therapy and impact on emotional health and lifestyle changes in the long term. Gene therapy was more accepted among patients with severe and uncontrolled disease. In-utero gene editing was not completely accepted because of safety and ethical issues. CONCLUSION: Patients with severe hemophilia perceive gene therapy as a potential cure, while gene editing was more controversial. Patients still have questions that remain to be answered regarding safety and efficacy that should be assessed with long-term follow up studies.

Multiple Stakeholder Views on Data Sharing in a Biobank in an Integrated Healthcare Delivery System: Implications for Biobank Governance.

BACKGROUND: Beginning in 2005, researchers at Kaiser Permanente Northern California (KPNC) Division of Research developed the Research Program on Genes, Environment, and Health (RPGEH), a research resource of linked biospecimens, health surveys, and electronic health records on more than 200,000 adult KPNC members. This study examined multiple stakeholders' values and preferences regarding protection of participants' privacy and wide sharing of participant data by RPGEH. METHODS: We conducted 45 semi-structured interviews in person or via phone and two focus groups with seven stakeholder groups, including RPGEH participants and decliners who are KPNC members, KPNC research scientists, external scientists, leadership, Human Subjects Research Protection Program staff, and RPGEH Community Advisory Panel members. RESULTS: Three major themes emerged related to: (1) perceived individual and social harms associated with data sharing; (2) concerns to address when governing access to RPGEH data; and (3) impact of a blurred boundary between research and clinical care in the context of biobanking. CONCLUSIONS: The study results were considered in the development of RPGEH data governance and motivated the inclusion of KPNC Community Advisory Panel members and ELSI experts on committees that evaluate data access proposals. Our findings can help inform other biobanks going through similar processes developing data sharing and access policies.

All in the family? Communication of cancer survivors with their families.

Families often bear the burden of communication about cancer risk, as well as support during and after treatment for cancer in family members. These activities are left up to survivors and their families, with little support or knowledge of useful methods. We present data on aspects of family that are most relevant to risk of cancer-related communication and health promotion among family members. Families (a survivor, one first-degree relative and one parent; n = 313 families) were enrolled in the survey-based study. We assessed multiple aspects of family communication about risk for melanoma among family participants. Families communicate less frequently than desired about cancer risk. Most families do identify a "family health provider" who keeps family data and serves a resource for family members. The reasons given for lack of family communication are diverse but many can be addressed as part of a family communication intervention. Families are poised to improve their family communication about cancer risk and so can play a role in increasing the health of their members.

Newborn Sequencing in Genomic Medicine and Public Health.

The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening.

Parental Views on Expanded Newborn Screening Using Whole-Genome Sequencing.

BACKGROUND AND OBJECTIVE: The potential application of whole-genome sequencing (WGS) to state-mandated standard newborn screening (NBS) challenges the traditional public health approach to NBS and raises ethical, policy, and clinical practice issues. This article examines the perspectives and values of diverse healthy pregnant women and parents of children diagnosed with a primary immunodeficiency disorder about traditional NBS and expanded NBS with the use of WGS. METHODS: We conducted 4 focus groups (3 in English and 1 in Spanish) with socioeconomically and ethnically diverse pregnant women (n = 26), and a comparison group with parents of children diagnosed with a primary immunodeficiency disorder (n = 5). RESULTS: Pediatric policy-relevant themes that emerged from our analysis of the focus group data are presented within 4 categories: (1) perspectives on traditional NBS, (2) informed consent, (3) return of results, and (4) storage and retrieval of results. Analyses indicate that study participants desired greater inclusion in the NBS process. Despite an optimistic orientation to the potential benefits and limited harms likely to result from genomic applications of NBS, parents voiced concerns about privacy and control over test results. Limited trust in the medical system and the state-run NBS program informed these concerns. CONCLUSIONS: Expanded NBS with WGS for pediatricians may require management of more genetic conditions, including mutations that convey risk to both the child and parents for adult-onset disorders, and an informed-consent process to manage the genomic data and storage of blood spots. Attention to how these technologies are understood in diverse populations is needed for effective implementation.