Genetics providers' perspectives on the use of digital tools in clinical practice.

PURPOSE: Digital tools are increasingly incorporated into genetics practice to address challenges with the current model of care. Yet, genetics providers' perspectives on digital tool use are not well characterized. METHODS: Genetics providers across Canada were recruited. Semistructured interviews were conducted to ascertain their perspectives on digital tool use and the clinical practice factors that might inform digital tool integration. A qualitative interpretive description approach was used for analysis. RESULTS: Thirty-three genetics providers across 5 provinces were interviewed. Participants had favorable attitudes toward digital tool use. They were open to using digital tools in the pretest phase of the genetic testing pathway and for some posttest tasks or in a hybrid model of care. Participants expressed that digital tools could enhance efficiency and allow providers to spend more time practicing at the top of scope. Providers also described the need for careful consideration of the potential impact of digitalization on the clinician-patient dynamic, access to and equity of care, and unintended digital burden on providers. CONCLUSION: Genetics providers considered digital tools to represent a viable solution for improving access, efficiency, and quality of care in genetics practice. Successful use of digital tools in practice will require careful consideration of their potential unintended impacts.

A Genomic Counseling Model for Population-Based Sequencing: A Pre-Post Intervention Study.

BACKGROUND: Novel uses of genome sequencing (GS) present an opportunity for return of results to healthy individuals, prompting the need for scalable genetic counseling strategies. We evaluate the effectiveness of a genomic counseling model (GCM) and explore preferences for GS findings in the general population. METHODS: Participants (N=466) completed GS and our GCM (digital genomics platform and group-based webinar), and indicated results preferences. Surveys were administered pre- (T0) and post- (T1) GCM. Change in knowledge and decisional conflict (DC) were evaluated using paired-sample T and Wilcoxon tests. Factors influencing knowledge and results preferences were evaluated using linear and logistic regression models. RESULTS: Participants were 56% female, 58% white, and 53% ≥40 years of age. Mean knowledge scores increased (Limitations: 3.73 to 5.63; benefits: 3.73 to 5.48, p<0.0001) and DC decreased (-21.9, p<0.0001) at T1 versus T0. Eighty-six percent of participants wished to learn all GS findings at T1 vs 78% at T0 (p<0.0001). Older age, negative/mixed attitudes toward genetics, and greater DC were associated with change in preferences post-intervention. CONCLUSION: In a population-based cohort undergoing GS interested in learning GS findings, our GCM increased knowledge and reduced DC, illustrating the GCM's potential effectiveness for GS counseling in the general population.

A model for the return and referral of all clinically significant secondary findings of genomic sequencing.

Secondary findings (SFs) identified through genomic sequencing (GS) can offer a wide range of health benefits to patients. Resource and capacity constraints pose a challenge to their clinical management; therefore, clinical workflows are needed to optimise the health benefits of SFs. In this paper, we describe a model we created for the return and referral of all clinically significant SFs, beyond medically actionable results, from GS. As part of a randomised controlled trial evaluating the outcomes and costs of disclosing all clinically significant SFs from GS, we consulted genetics and primary care experts to determine a feasible workflow to manage SFs. Consensus was sought to determine appropriate clinical recommendations for each category of SF and which clinician specialist would provide follow-up care. We developed a communication and referral plan for each category of SFs. This involved referrals to specialised clinics, such as an Adult Genetics clinic, for highly penetrant medically actionable findings. Common and non-urgent SFs, such as pharmacogenomics and carrier status results for non-family planning participants, were directed back to the family physician (FP). SF results and recommendations were communicated directly to participants to respect autonomy and to their FPs to support follow-up of SFs. We describe a model for the return and referral of all clinically significant SFs to facilitate the utility of GS and promote the health benefits of SFs. This may serve as a model for others returning GS results transitioning participants from research to clinical settings.

Finding the sweet spot: a qualitative study exploring patients' acceptability of chatbots in genetic service delivery.

Chatbots, web-based artificial intelligence tools that simulate human conversation, are increasingly in use to support many areas of genomic medicine. However, patient preferences towards using chatbots across the range of clinical settings are unknown. We conducted a qualitative study with individuals who underwent genetic testing for themselves or their child. Participants were asked about their preferences for using a chatbot within the genetic testing journey. Thematic analysis employing interpretive description was used. We interviewed 30 participants (67% female, 50% 50 + years). Participants considered chatbots to be inefficient for very simple tasks (e.g., answering FAQs) or very complex tasks (e.g., explaining results). Chatbots were acceptable for moderately complex tasks where participants perceived a favorable return on their investment of time and energy. In addition to achieving this "sweet spot," participants anticipated that their comfort with chatbots would increase if the chatbot was used as a complement to but not a replacement for usual care. Participants wanted a "safety net" (i.e., access to a clinician) for needs not addressed by the chatbot. This study provides timely insights into patients' comfort with and perceived limitations of chatbots for genomic medicine and can inform their implementation in practice.

Great expectations: patients' preferences for clinically significant results from genomic sequencing.

We aimed to describe patient preferences for a broad range of secondary findings (SF) from genomic sequencing (GS) and factors driving preferences. We assessed preference data within a trial of the Genomics ADvISER, (SF decision aid) among adult cancer patients. Participants could choose from five categories of SF: (1) medically actionable; (2) polygenic risks; (3) rare diseases; (4) early-onset neurological diseases; and (5) carrier status. We analyzed preferences using descriptive statistics and drivers of preferences using multivariable logistic regression models. The 133 participants were predominantly European (74%) or East Asian or mixed ancestry (13%), female (90%), and aged > 50 years old (60%). The majority chose to receive SF. 97% (129/133) chose actionable findings with 36% (48/133) choosing all 5 categories. Despite the lack of medical actionability, participants were interested in receiving SF of polygenic risks (74%), carrier status (75%), rare diseases (59%), and early-onset neurologic diseases (53%). Older participants were more likely to be interested in receiving results for early-onset neurological diseases, while those exhibiting lower decisional conflict were more likely to select all categories. Our results highlight a disconnect between cancer patient preferences and professional guidelines on SF, such as ACMG's recommendations to only return medically actionable secondary findings. In addition to clinical evidence, future guidelines should incorporate patient preferences.

Genome screening, reporting, and genetic counseling for healthy populations.

Rapid advancements of genome sequencing (GS) technologies have enhanced our understanding of the relationship between genes and human disease. To incorporate genomic information into the practice of medicine, new processes for the analysis, reporting, and communication of GS data are needed. Blood samples were collected from adults with a PCR-confirmed SARS-CoV-2 (COVID-19) diagnosis (target N = 1500). GS was performed. Data were filtered and analyzed using custom pipelines and gene panels. We developed unique patient-facing materials, including an online intake survey, group counseling presentation, and consultation letters in addition to a comprehensive GS report. The final report includes results generated from GS data: (1) monogenic disease risks; (2) carrier status; (3) pharmacogenomic variants; (4) polygenic risk scores for common conditions; (5) HLA genotype; (6) genetic ancestry; (7) blood group; and, (8) COVID-19 viral lineage. Participants complete pre-test genetic counseling and confirm preferences for secondary findings before receiving results. Counseling and referrals are initiated for clinically significant findings. We developed a genetic counseling, reporting, and return of results framework that integrates GS information across multiple areas of human health, presenting possibilities for the clinical application of comprehensive GS data in healthy individuals.

"I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing.

PURPOSE: We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS). METHODS: Qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Thematic analysis employing constant comparison was used. Two coders coded transcripts, with use of a third coder to resolve conflicts. RESULTS: 25 patients participated: female (22), >50 years (18), European (12), Ashkenazi Jewish (5), Middle Eastern (3), or other ethnicity (5), with breast cancer history (20). Patients' perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very "useful" and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary variants of uncertain significance results without clinical action perceived results as "concerning," leading to harms, such as hypervigilance about cancer symptoms. Overall, having supportive relatives or providers enhanced perceptions of utility. CONCLUSION: Patients' perceptions of cancer GS results hinged on whether they triggered clinical management. Consequently, patients who received results without clinical action became hypervigilant, experiencing harms. Our findings call for a need to develop practice interventions to support patients with cancer undergoing GS.

How do members of the public expect to use variants of uncertain significance in their health care? A population-based survey.

PURPOSE: Genomic sequencing can generate complex results, including variants of uncertain significance (VUS). In general, VUS should not inform clinical decision-making. This study aimed to assess the public's expected management of VUS. METHODS: An online, hypothetical survey was conducted among members of the Canadian public preceded by an educational video. Participants were randomized to 1 of 2 arms, VUS or pathogenic variant in a colorectal cancer gene, and asked which types of health services they expected to use for this result. Expected health service use was compared between randomization arms, and associations between participants' sociodemographic characteristics, attitudes, and medical history were explored. RESULTS: Among 1003 respondents (completion rate 60%), more participants expected to use each type of health service for a pathogenic variant than for a VUS. However, a considerable proportion of participants expected to request monitoring (73.4%) and consult health care providers (60.9%) for a VUS. There was evidence to support associations between expectation to use health services for a VUS with family history of genetic disease, family history of cancer, education, and attitudes toward health care and technology. CONCLUSION: Many participants expected to use health services for a VUS in a colorectal cancer predisposition gene, suggesting a potential disconnect between patients' expectations for VUS management and guideline-recommended care.

A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

"Game Changer": Health Professionals' Views on the Clinical Utility of Circulating Tumor DNA Testing in Hereditary Cancer Syndrome Management.

BACKGROUND: We explored health professionals' views on the utility of circulating tumor DNA (ctDNA) testing in hereditary cancer syndrome (HCS) management. MATERIALS AND METHODS: A qualitative interpretive description study was conducted, using semi-structured interviews with professionals across Canada. Thematic analysis employing constant comparison was used for analysis. 2 investigators coded each transcript. Differences were reconciled through discussion and the codebook was modified as new codes and themes emerged from the data. RESULTS: Thirty-five professionals participated and included genetic counselors (n = 12), geneticists (n = 9), oncologists (n = 4), family doctors (n = 3), lab directors and scientists (n = 3), a health-system decision maker, a surgeon, a pathologist, and a nurse. Professionals described ctDNA as "transformative" and a "game-changer". However, they were divided on its use in HCS management, with some being optimistic (optimists) while others were hesitant (pessimists). Differences were driven by views on 3 factors: (1) clinical utility, (2) ctDNA's role in cancer screening, and (3) ctDNA's invasiveness. Optimists anticipated ctDNA testing would have clinical utility for HCS patients, its role would be akin to a diagnostic test and would be less invasive than standard screening (eg imaging). Pessimistic participants felt ctDNA testing would add limited utility; it would effectively be another screening test in the pathway, likely triggering additional investigations downstream, thereby increasing invasiveness. CONCLUSIONS: Providers anticipated ctDNA testing will transform early cancer detection for HCS families. However, the contrasting positions on ctDNA's role in the care pathway raise potential practice variations, highlighting a need to develop evidence to support clinical implementation and guidelines to standardize adoption.