Myers, Melanie F.

This secondary analysis of a nonrandomized clinical trial identifies which participant characteristics were associated with selection of centralized or remote trial engagement.

Collaboration between biobanks and research teams is essential for advancing scientific research, particularly in studies involving human subjects; however, various challenges can hinder success. We shed light on key obstacles and challenges encountered during a partnership between a clinical trial and an institutional biobank at a pediatric hospital. In aiming to recruit pediatric biobank participants for a genomic clinical research study, key challenges included low-yield recruitment tactics, independent operations and structures of the biobank and research teams, and transition to a new biobank model resulting in struggles with participant reengagement. This article explores some of the obstacles experienced by the research and biobanks teams, while providing key lessons aimed at guiding others in planning future collaborations for trial recruitment, enrollment, and implementation. We also highlight the significant benefits that can arise when biobanks and research teams work together strategically.

AbstractAlthough guidelines have historically recommended deferring decisions about learning genomic information for conditions not actionable in childhood until adulthood, youth have increasing access to personal genomic information through research, clinical, and direct‐to‐consumer testing. However, little is known about young people's reactions to, and perceived future utility of learning genomic information actionable in adulthood. We conducted qualitative interviews with 28 youth ages 15–22 without clinical indications for genetic screening who, through enrollment in a genomic decision‐making research study, learned they were carriers of an autosomal recessive condition, or anticipated being carriers but received negative results. Semi‐structured interviews occurred virtually between 3 and 16 months after the return of results. Interpretative description guided deductive and inductive coding of transcripts. Of the 28 participants, 21 received positive carrier results, and 7 received negative results. Although some carriers felt the result was unexpected, they expressed relief overall and did not feel worried about their result. Participants with negative results also felt relief about their results. All participants correctly described what a carrier result means, but some carriers could not remember the condition associated with their result. No participant regretted learning personal genomic information, and all reported their results helped them better understand risks to future children. Carriers who perceived the condition for which they were carriers as more severe and/or those familiar with the condition were more likely to remember their result and consider future reproductive options. Carriers also felt testing at their respective age allowed increased familiarity with results and more time to gather information and decide on the personal utility of the information. Our findings suggest early access to genomic information for some youth may allow integration of carrier information over time with minimal adverse effects. More research is needed to assess long‐term outcomes among carriers.

AbstractWith increasing opportunities for minors to undergo genomic testing, factors influencing young people's decision stability and instability regarding genomic testing are unclear. This interpretive description study examines decision stability when adolescents (13–17) and young adults (18–21) decide whether to learn genetic testing results. Adolescents and young adults enrolled in a clinical trial chose whether they wanted to learn genetic testing results and could modify their decisions during a study visit or 2 weeks later. A purposive sample of clinical trial participants was invited to participate in an interview exploring their decision preferences, confidence level, and factors impacting decision stability. Twenty‐two participants chose to learn all (n = 7), some (n = 7), or no genetic test results (n = 8). Perceptions of the impact of personal genetic information on one's quality of life and sense of reproductive goals and responsibilities were driving factors for people who chose to learn no or some genetic results, while curiosity influenced those who chose to learn all. Prior health and healthcare experiences and others' influence also factored into decision‐making about receiving results. Decision stability varied among individuals but increased over time and was positively influenced by parents, baseline decision confidence, and fear of missing out on the opportunity to learn genetic information. Participants felt favorably about the opportunity to change their decision 2 weeks after the study visit. Among study participants, decision stability was high, as was satisfaction with decisions regarding how much personal genetic information to learn. The results suggest that adolescent and young adult genetic research participants may experience high decision stability and confidence in making choices regarding personal genetic testing, especially when a window of opportunity for change is available. Researchers and clinicians should consider the benefits and challenges of offering multiple checkpoints to bolster decision stability.

AbstractYoung adults have increasing genomic testing opportunities; however, little is known about how equipped they feel about making decisions to learn personal genomic information. We conducted qualitative interviews with 19 young adults, ages 18–21 years old, enrolled in a research study where they made decisions about learning personal genomic risk for developing preventable, treatable, and adult‐onset conditions and carrier status for autosomal recessive conditions. Participants had the option to include a parent in their study visit and the decision‐making process. The goal of this project was to explore young adults' reasons for involving or not involving a parent in the study and to assess young adults' perspectives about parental roles in their healthcare. Nine participants included a parent in the study and ten did not include a parent. Eleven participants received genomic test results before the interview, while eight participants had not yet received their results at the time of the interview. The study team developed a coding guide and coded interview transcripts inductively and deductively using an interpretive descriptive‐analytic approach. Logistical issues dominated solo participants' reasons for not involving a parent in the study, whereas those who involved a parent often cited a close relationship with the parent and the parent's previous involvement in the participant's healthcare as reasons for involving them. Both groups of participants described gradually transitioning to independent healthcare decision‐making with age and felt their comfort in medical decision‐making depends on the severity of and their familiarity with the situation. Participants recommended that future genomic researchers or clinicians give young adults the option to involve a parent or friend as a support person in research or clinical visits. Although young adults may have different journeys toward independent healthcare decision‐making, some may benefit from continued parental or peer involvement after reaching the age of legal adulthood.

To understand whether they found a two-step decision process helpful and why, adolescent-parent dyads participating in a study investigating return of genomic testing results were asked about their decision-making experience. Responses were qualitatively coded and analyzed using thematic analysis. Adolescents and parents found both joint and independent decision-making stages helpful. Regarding independent decision-making, adolescents appreciated exercising independence, while parents valued both adolescent and parental independence. Joint decision-making allowed each to hear the other's viewpoints. Some found joint decision-making irrelevant but recognized it might help others. Overall, adolescents and parents had similar reasons for finding the two-step decision-making process helpful. Our findings support using such a process for engaging parents and adolescents in challenging research and clinical decisions.

Abstract Background To protect minors’ future autonomy, professional organizations have historically discouraged returning predictive adult-onset genetic test results and carrier status to children. Recent clinical guidance diverges from this norm, suggesting that when minors have genomic sequencing performed for clinical purposes, parents and children should have the opportunity to learn secondary findings, including for some adult-onset conditions. While parents can currently opt in or out of receiving their child’s secondary findings, the American Society of Human Genetics Workgroup on Pediatric Genetic and Genomic Testing suggests including adolescents in the decision-making process. However, it is not clear what factors young people consider when given the opportunity to learn genetic findings for themselves. We are examining adolescents’, young adults’, and parents’ (if applicable) decisions about learning genomic information for the adolescent. Methods We are enrolling assenting (ages 13–17) adolescents and consenting (ages 18–21) young adults in a prospective genomic screening study to assess the choices they make about receiving individual genomic results. Participants use an online tool to indicate whether they want to learn their personal genetic risk for specific preventable, treatable, and adult-onset conditions, as well as carrier status for autosomal recessive conditions. We are examining 1) how choices differ between adolescent and young adult cohorts (as well as between adolescents/young adults and parents) and 2) decisional conflict and stability across study timepoints. Results are returned based on participants’ choices. Qualitative interviews with a subset of participants explore decisional stability, adolescent/young adult engagement with parents in decision-making, and the impact of learning pathogenic/likely pathogenic and carrier results. Discussion This study explores decision making and decision stability between adolescents and parents (where applicable), as well as the ethical implications and impact of return of clinical-grade genetic research results to adolescents and young adults. The results of this study will contribute empirical evidence to support best practices and guidance on engaging young people in genetic research studies and clinical care that offer return of results. Trial Registration: ClinicalTrials.gov Identifier: NCT04481061. Registered 22 July 2020.

Purpose: The electronic Medical Records and Genomics (eMERGE) Phase III study was undertaken to assess clinical utility of returning medically actionable genomic screening results. We assessed pediatric clinical outcomes following return of pathogenic/likely pathogenic (P/LP) variants in autosomal dominant conditions with available effective interventions. Methods: The two eMERGE III pediatric sites collected outcome data and assessed changes in medical management at 6 and 12 months. Results: We returned P/LP results to 29 participants with outcome data. For 23 of the 29 participants, the P/LP results were previously unknown. Five of the 23 participants were already followed for conditions related to the P/LP variant. Of those receiving novel results and not being followed for the condition related to the P/LP result (n = 18), 14 (77.8%) had a change in healthcare after return of results (RoR). Following RoR, cascade testing of family members occurred for 10 of 23 (43.5%). Conclusions: The most common outcomes post-RoR included imaging/laboratory testing and health behavior recommendations. A change in healthcare was documented in 77.8% of those receiving results by 6 months. Our findings demonstrate how return of genomic screening results impacts healthcare in pediatric populations.

Abstract The public health impact of genomic screening can be enhanced by cascade testing. However, cascade testing depends on communication of results to family members. While the barriers and facilitators of family communication have been researched following clinical genetic testing, the factors impacting the dissemination of genomic screening results are unknown. Using the pragmatic Electronic Medical Records and Genomics Network‐3 (eMERGE‐3) study, we explored the reported sharing practices of participants who underwent genomic screening across the United States. Six eMERGE‐3 sites returned genomic screening results for mostly dominant medically actionable disorders and surveyed adult participants regarding communication of results with first‐degree relatives. Across the sites, 279 participants completed a 1‐month and/or 6‐month post‐results survey. By 6 months, only 34% of the 156 respondents shared their results with all first‐degree relatives and 4% did not share with any. Over a third (39%) first‐degree relatives were not notified of the results. Half (53%) of participants who received their results from a genetics provider shared them with all first‐degree relatives compared with 11% of participants who received their results from a non‐genetics provider. The most frequent reasons for sharing were a feeling of obligation (72%) and that the information could help family members make medical decisions (72%). The most common reasons indicated for not sharing were that the family members were too young (38%), or they were not in contact (25%) or not close to them (25%). These data indicate that the professional returning the results may impact sharing patterns, suggesting that there is a need to continue to educate healthcare providers regarding approaches to facilitate sharing of genetic results within families. Finally, these data suggest that interventions to increase sharing may be universally effective regardless of the origin of the genetic result.

AbstractPopulation‐based genomic screening has the potential to improve health outcomes by identifying genetic causes of disease before they occur. While much attention has been paid to supporting the needs of the small percentage of patients who will receive a life‐altering positive genomic screening result that requires medical attention, little attention has been given to the communication of negative screening results. As there are currently no best practices for returning negative genomic screening results, we drew on experiences across the electronic medical records and genomics (eMERGE) III Network to highlight the diversity of reporting methods employed, challenges encountered in reporting negative test results, and “lessons learned” across institutions. A 60‐item survey that consisted of both multiple choice and open‐ended questions was created to gather data across institutions. Even though institutions independently developed procedures for reporting negative results, and had very different study populations, we identified several similarities of approach, including but not limited to: returning results by mail, placing results in the electronic health record via an automated process, reporting results to participants' primary care provider, and providing genetic counseling to interested patients at no cost. Differences in procedures for reporting negative results included: differences in terminology used to describe negative results, definitions of negative results, guidance regarding the meaning of negative results for participants and their family members, and recommendations for clinical follow up. Our findings highlight emerging practices for reporting negative genomic screening results and highlight the need to create patient education and clinical support tools for reporting negative screening results.