A novel online genomic counseling and variant interpretation certificate: Learning design, learning analytics, and evaluation.

In this paper we describe the analysis, planning, design, development, implementation and evaluation of a new online Graduate Certificate in Genomic Counselling and Variant Interpretation (GCGCVI) at The University of British Columbia (UBC). Genetic counselling is now a prerequisite for diagnostic genomic testing in many countries, demanding that genetic counselling practitioners have up-to-the-moment genomic counselling skills and knowledge. Current practitioners reported a desire for more training in this rapidly developing field: our international survey revealed substantial interest in online continuing education addressing themes such as testing and clinical bioinformatics, applied variant interpretation, evidence-based genomic counselling, and other emerging genomic topics. However, our market analysis found no post-graduate program globally that offered such training. To fill this gap, our oversight team of genetic counsellors and geneticists therefore guided development of curriculum and materials, and online learning specialists developed rigorous interactive asynchronous online graduate courses through collaboration with subject matter experts, following best practices in online learning design. Since launch in September 2020, we have gathered learner feedback using surveys and focus groups, and we have used learning analytics to understand how learners engaged with each other and with course materials. Together, these have helped us understand learner behaviour and guide the continuous process of design improvement to support the learning goals of this audience of professional learners. Our courses have been reviewed and approved by the UBC Faculty of Medicine, UBC Senate, and the Province of British Columbia Ministries of Advanced Education and Health, and assessed by the National Society of Genetic Counselors (NSGC, USA) and the Canadian Association of Genetic Counsellors (CAGC) to enable learners to receive North American continuing education credits. To date, 151 individuals from 18 countries have succeeded in one or more course and 43 have completed the entire certificate.

Genetic counselling resources in non-english languages: A scoping review.

Objective: Genetic counselling is essential for individuals seeking genetic or genomic testing. Whereas innovative strategies for GC delivery are being explored to meet the growing demand on the clinical genetics workforce, it is essential to consider the unique needs of culturally and linguistically diverse populations. Methods: We conducted a scoping review to examine the extent, range, and gaps in the body of non-English, patient-facing educational resources available for Limited English Proficient (LEP) patients accessing clinical genetics and genomics services. Results: The literature search returned 246 unique resources, most available in several languages. Forty-six languages were represented, with Spanish, Russian, and French being the most common. Resources were in various formats and were of varying quality. Conclusions: There is a lack of high-quality supplementary genetics education material available in languages other than English, which limits the quality-of-care that LEP families may receive compared to their English-speaking counterparts. Of equal concern is the difficulty in finding existing resources and in determining their quality. Innovation: This research highlights the important need for genetics education material that is of good quality in languages other than English and the challenges associated with identifying this material. A central, curated repository, perhaps sponsored by a genetic counselling organization, would be of great benefit to help genetic counsellors meet the needs of their culturally and linguistically diverse patients.

The long-term impact of receiving incidental findings on parents undergoing genome-wide sequencing.

Genome-wide (exome or genome) sequencing (GWS) has the potential to detect incidental findings (IFs): variants unrelated to the primary indication for testing that may be of medical or personal utility. As GWS becomes increasingly common in clinical practice, it is important to understand the impact of IFs on the individuals and their families. Our goal was to explore the immediate and long-term lived experience of individuals who received IFs as part of diagnostic GWS. We interviewed parents who received an IF as part of the CAUSES translational research study at Children's and Women's Health Centre of British Columbia. Five hundred families were offered trio-based GWS for their child with a suspected, undiagnosed genetic condition. Nine hundred and one of the 1000 parents chose to find out about IFs and 21 parents received an IF for themselves. Twelve of these parents participated in this study. They were interviewed an average of 2.3 years after the IFs were returned. Thematic analysis of transcribed interviews revealed that the participants' decisions and motivations to receive IFs were influenced by personal values and beliefs and by having a child with a suspected genetic condition. Participants' experiences were also influenced by the type of IF received, having a personal or family history of a related condition, their personal interpretation and perceived utility of the information, and the impact of the IF on other family members. Participants expressed either no regret or mild decisional regret on the Decisional Regret Scale. Two years post results, most participants reported little negative impact from receiving the IF. The utility of the information varied: some reported lifestyle changes and proactive screening, while others felt the information may be more relevant in the future. Understanding the immediate and longer term impact of receiving IFs from GWS can inform both pre- and post-test genetic counseling.

After genomic testing results: Parents' long-term views.

Many parents are motivated to pursue genome-wide (exome or genome) sequencing to find a diagnosis for their child with a suspected but undiagnosed genetic condition. However, the impact of the genomic test extends beyond the provision of results and the so-called 'diagnostic odyssey'. Our goal was to quantify post-test decisional regret and characterize long-term, post-test experiences and unmet needs of the parents of children with suspected genetic diseases after they had received the results of genome-wide sequencing. Study participants were parents of children who underwent trio genome-wide sequencing as part of the CAUSES research study at Children's & Women's Health Centre of British Columbia. About half of the participants received a definite or likely genetic diagnosis after clinical interpretation of the genome-wide sequencing results. Parents who participated in the current study (n = 121) completed the Decisional Regret Scale four weeks after receiving results. A subset of these parents (n = 32) had semi-structured interviews a median of 7 months (range 3-20 months) after results disclosure and post-test genetic counseling. Most parents expressed either no regret or mild regret about having undergone genome-wide sequencing on both the Decisional Regret Scale and in the interviews. Parents whose children did not receive a genetic diagnosis were slightly more likely to have decisional regret on this quantitative scale. Analysis of transcribed interviews revealed the following major themes: (a) a lack of decisional conflict around having the testing; (b) a lack of decisional regret post-testing; (c) expressions of both relief and continued uncertainty around the meaning of a genetic diagnosis; (d) expression of initial disappointment and evolving interpretation surrounding a result yielding no genetic diagnosis; and (e) needing time to absorb the test results. Our results suggest that parents need time to absorb the testing results and that long-term post-test counseling, including acknowledging feelings of relief, loss, and disappointment, may help parents adapt to the genomic test results and assist families to anticipate and plan for the next steps in their child's medical trajectory, whether or not a diagnosis is found.

A personalized genomic results e-booklet, co-designed and pilot-tested by families.

Objective: To develop and evaluate a personalizable genomic results e-booklet that helps families understand their genomic testing results and navigate available resources. Methods: The need for the Genomics Results e-Booklet was identified by families, after which this tool was developed by a team of clinical researchers and three parent-advisors. We customized the genomic results e-booklet for 50 families participating in a genomic sequencing research study. We conducted an assessment using a 19-question survey and semi-structured interviews to elicit feedback and iteratively improve the tool. Results: 25 users provided feedback via questionnaires and seven respondents were interviewed. Genomic Results e-Booklet recipients responded favorably: 96% of participants stated that it helped them remember information shared during their results appointment, 80% said it had or would help them communicate their results with other healthcare providers, 68% felt that it helped to identify and guide their next steps, and 72% anticipated that the e-booklet would have future utility. Conclusion: The Genomic Results e-Booklet is a patient and family-oriented resource that complements post-test genetic counselling. Innovation: Compared to traditional laboratory reports and clinical letters, the Genomics Results e-Booklet is patient-conceived and patient-centered, and allows clinicians to efficiently personalize content and prioritize patient understanding and support.

Utilization and uptake of clinical genetics services in high-income countries: A scoping review.

Ongoing rapid growth in the need for genetic services has the potential to severely strain the capacity of the clinical genetics workforce to deliver this care. Unfortunately, assessments of the scale of this health policy challenge and potential solutions are hampered by the lack of a consolidated evidence base on the growth in genetic service utilization. To enable health policy research and strategic planning by health systems in this area, we conducted a scoping review of the literature on the utilization and uptake of clinical genetics services in high-income countries published between 2010 and 2018. One-hundred-and-ninety-five unique studies were included in the review. Most focused on cancer (85/195; 44%) and prenatal care (50/195; 26%), which are consistently the two areas with the greatest volume of genetic service utilization in both the United States and other high-income countries. Utilization and uptake rates varied considerably and were influenced by contextual factors including health system characteristics, provider knowledge, and patient preferences. Moreover, growth in genetic service utilization appears to be driven to a significant degree by technological advances and the integration of new tests into clinical care. Our review highlights both the policy challenge posed by the rapid growth in the utilization of genetic services and the variability in this trend across clinical indications and health systems.

Correction: The composition and capacity of the clinical genetics workforce in high-income countries: a scoping review.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The composition and capacity of the clinical genetics workforce in high-income countries: a scoping review.

As genetics becomes increasingly integrated into all areas of health care and the use of complex genetic tests continues to grow, the clinical genetics workforce will likely face greatly increased demand for its services. To inform strategic planning by health-care systems to prepare to meet this future demand, we performed a scoping review of the genetics workforce in high-income countries, summarizing all available evidence on its composition and capacity published between 2010 and 2019. Five databases (MEDLINE, Embase, PAIS, CINAHL, and Web of Science) and gray literature sources were searched, resulting in 162 unique studies being included in the review. The evidence presented includes the composition and size of the workforce, the scope of practice for genetics and nongenetics specialists, the time required to perform genetics-related tasks, case loads of genetics providers, and opportunities to increase efficiency and capacity. Our results indicate that there is currently a shortage of genetics providers and that there is a lack of consensus about the appropriate boundaries between the scopes of practice for genetics and nongenetics providers. Moreover, the results point to strategies that may be used to increase productivity and efficiency, including alternative service delivery models, streamlining processes, and the automation of tasks.

The cost trajectory of the diagnostic care pathway for children with suspected genetic disorders.

PURPOSE: This study describes the cost trajectory of the standard diagnostic care pathway for children with suspected genetic disorders in British Columbia, Canada. METHODS: Average annual per-patient costs were estimated using medical records review and a caregiver survey for a cohort of 498 children referred to BC Children's and Women's Hospitals (C&W) with unexplained intellectual disability (the TIDE-BC study) and families enrolled in the CAUSES study, which offered diagnostic genome-wide sequencing (GWS; exome and genome sequencing) to 500 families of children with suspected genetic disorders. RESULTS: Direct costs peaked in the first year of patients' diagnostic odyssey, with an average of C$2257 per patient (95% confidence interval [CI] C$2074, C$2441) for diagnostic testing and C$631 (95% CI C$543, C$727) for specialist consultations at C&W. In subsequent years, direct costs accrued at a constant rate, with an estimated annual per-patient cost of C$511 (95% CI C$473, C$551) for diagnostic testing and C$334 (95% CI C$295, C$369) for consultations at C&W. Travel costs and caregiver productivity loss associated with attending diagnosis-related physician appointments averaged C$1907/family/year. CONCLUSIONS: The continuing long-term accrual of costs by undiagnosed patients suggests that economic evaluations of diagnostic GWS services should use longer time horizons than have typically been used.

Indigenous Peoples and genomics: Starting a conversation.

Compared to European ancestral groups, Indigenous Canadians are more likely to have uninterpretable genome-wide sequencing results due to non-representation in reference databases. We began a conversation with Indigenous Canadians to raise awareness and give voice to this issue. We co-created a video explaining genomic non-representation that included diverse Indigenous view-points. We audio-recorded the focus groups including 30 First Nations, Métis, and Inuit individuals living in Greater Vancouver. After watching an introductory video explaining genomic testing, participants discussed issues surrounding collecting Indigenous genomic data, its control, and usage. Transcripts were analyzed, and participants' quotes representing main themes were incorporated into the introductory video. Indigenous participants discussed data interpretation and gave approval for quote usage. The 20 participants who provided feedback concurred with the thematic interpretation: Systemic racism interlaced most conversations, particularly within the theme of trust. Themes of governance emphasized privacy and fear of discrimination. Some participants thought a separate, Indigenous-controlled database was essential; others recognized advantages of international databases. The theme of implementation included creative ideas to collect Indigenous genomes, but prior approval from Indigenous leaders was emphasized. The final video (https://youtu.be/-wivIBDjoi8) was shared with participants to use as they wish to promote awareness and ongoing discussion of genomic diagnostic inequity.

Assessing Shared Decision-Making Clinical Behaviors Among Genetic Counsellors.

Shared decision-making (SDM) is a collaborative approach in which clinicians educate, support, and guide patients as they make informed, value-congruent decisions. SDM improves patients' health-related outcomes through increasing knowledge, reducing decisional conflict, and enhancing experience of care. We measured SDM in genetic counselling appointments with 27 pregnant women who were at increased risk to have a baby with a genetic abnormality. The eight experienced genetic counsellors who participated had no specific SDM training and were unaware that SDM was being assessed. Audio transcripts of appointments were scored using 'Observing Patient Involvement in Decision Making' (OPTION12). Patients' anxiety and decisional conflict were also assessed. The genetic counsellors' mean OPTION12 score was 42.4% (SD 9.0%; possible range 0-100%). Specific SDM behaviours that scored highest included introducing the concept of equipoise and listing all options with their pros and cons. Behaviours that scored lowest included eliciting patients' preferred approach to receiving information and desired degree of involvement in decision-making. Patients' levels of anxiety and decisional conflict were unassociated with genetic counsellors' OPTION12 scores. Some SDM behaviours were better demonstrated in this prenatal genetic counselling study than others. Formal training of genetic counsellors in SDM may enhance use of this approach in their professional practice.

Assessing an Interactive Online Tool to Support Parents' Genomic Testing Decisions.

Clinical use of genome-wide sequencing (GWS) requires pre-test genetic counseling, but the availability of genetic counseling is limited. We developed an interactive online decision-support tool, DECIDE, to make genetic counseling, patient education, and decision support more readily available. We performed a non-inferiority trial comparing DECIDE to standard genetic counseling to assess the clinical value of DECIDE for pre-GWS counseling. One hundred and six parents considering GWS for their children with epilepsy were randomized to conventional genetic counseling or DECIDE. Following the intervention, we measured parents' knowledge and empowerment and asked their opinions about using DECIDE. Both DECIDE and conventional genetic counseling significantly increased parents' knowledge, with no difference between groups. Empowerment also increased but by less than 2% in each group. Parents liked using DECIDE and found it useful; 81% would recommend it to others; 49% wished to use it along with a genetic counselor; 26% of parents preferred to see a genetic counselor; 7% preferred DECIDE alone; and 18% had no preference. DECIDE appears equivalent to genetic counseling at conveying information. In addition, it was highly acceptable to the majority of study participants, many of whom indicated that it was useful to their decision-making. Use of DECIDE as a pre-test tool may extend genetic counseling resources.

Serial MRIs provide novel insight into natural history of optic pathway gliomas in patients with neurofibromatosis 1.

BACKGROUND: Optic pathway gliomas (OPGs) are present in 20% of children with neurofibromatosis 1 (NF1) but are less frequently observed in adults. Our goal was to determine the natural history of OPGs in children and adults with NF1. RESULTS: We analyzed the features of OPGs and other intracranial lesions on 1775 head MRI scans of 562 unselected adults and children with NF1 collected between 2003 and 2015. 52 (9.3%) of 562 patients in this study had an OPG diagnosed on their MRI. The median age at first scan with an OPG present was 12.7 years. Of the 52 OPG patients, the intraorbital optic nerves were affected in 29 patients (56%), the prechiasmatic optic nerves were affected in 32 patients (62%), the optic chiasm was affected in 17 patients (33%) and the optic radiations were affected in 19 patients (37%). 29 patients had two or more areas affected. One patient had a newly-appearing OPG, and 1 patient showed progression. The rate of progression over 5 years was 2.4% (95% CI: 0.4% to 16%). Four patients showed partial regression of their OPGs, but we observed no case of complete regression during this study. The rate of regression over 5 years was 8.9% (95% confidence intervals: 2.8% to 26%). We found the presence of UBOs and the presence of OPGs in individual patients to be highly associated (p = 0.0061). CONCLUSION: OPGs are more common in older adults with NF1 than previously thought. The occurrences of unidentified bright objects (UBOs) and asymptomatic OPGs are associated with each other. This suggests the possibility that OPGs that remain asymptomatic may differ pathogenically from those that become symptomatic.

Non-optic glioma in adults and children with neurofibromatosis 1.

BACKGROUND: Non-optic gliomas occur in 5% of children with NF1, but little is known about these tumours in adults. We aimed to investigate progression, spontaneous regression and the natural history of non-optic gliomas in adults and compare these findings to the results found in children. RESULTS: One thousand seven hundred twenty-two brain MRI scans of 562 unselected individuals with NF1 were collected at the NF outpatient department of the University Hospital Hamburg-Eppendorf between 2003 and 2015. The number of scans per patient ranged from one to 12; patients were followed for a median of 3.7 years. We identified 24 patients (4.3%) with non-optic gliomas. Median age at first scan with glioma was 21.2 years, much higher than in previous publications. Only seven of the 24 non-optic glioma patients were symptomatic. Five of 24 patients had multiple non-optic gliomas. Four individuals developed a new tumour, and 4 cases showed progression. The risk of new tumour development was 0.19% (95% confidence interval 0.06% to 0.52%) per patient year of follow-up for patients over 10 years. The rate of progressing non-optic gliomas per patient year of follow-up in the first 5 years after tumour diagnosis was 4.7% (95% confidence interval 1.5% to 12%). CONCLUSIONS: Non-optic gliomas are twice as common in an unselected cohort of NF1 patients as previously reported. This is likely due to increased frequency of diagnosis of asymptomatic tumours when routine MRIs are performed and a higher prevalence in older individuals.

DECIDE: a Decision Support Tool to Facilitate Parents' Choices Regarding Genome-Wide Sequencing.

We describe the rationale, development, and usability testing for an integrated e-learning tool and decision aid for parents facing decisions about genome-wide sequencing (GWS) for their children with a suspected genetic condition. The online tool, DECIDE, is designed to provide decision-support and to promote high quality decisions about undergoing GWS with or without return of optional incidental finding results. DECIDE works by integrating educational material with decision aids. Users may tailor their learning by controlling both the amount of information and its format - text and diagrams and/or short videos. The decision aid guides users to weigh the importance of various relevant factors in their own lives and circumstances. After considering the pros and cons of GWS and return of incidental findings, DECIDE summarizes the user's responses and apparent preferred choices. In a usability study of 16 parents who had already chosen GWS after conventional genetic counselling, all participants found DECIDE to be helpful. Many would have been satisfied to use it alone to guide their GWS decisions, but most would prefer to have the option of consulting a health care professional as well to aid their decision. Further testing is necessary to establish the effectiveness of using DECIDE as an adjunct to or instead of conventional pre-test genetic counselling for clinical genome-wide sequencing.

Parents' Perspectives on Supporting Their Decision Making in Genome-Wide Sequencing.

PURPOSE: The purpose of this study was to explore parents' perceptions of their decisional needs when considering genome-wide sequencing (GWS) for their child. This is a partial report and focuses on how parents prefer to receive education and information to support their decision making about GWS. DESIGN: This study adopted an interpretive description qualitative methodological approach and used the concept of shared decision making and the Ottawa Decision Support Framework. METHODS: Participants were parents who had already consented to GWS, and had children with undiagnosed conditions that were suspected to be genetic in origin. Fifteen parents participated in a focus group or individual interview. Transcriptions were analyzed concurrently with data collection, iteratively, and constantly compared to one another. Repeat interviews were conducted with five of the parents to confirm, challenge, or expand on the developing concepts. FINDINGS: Participants felt that their decision to proceed with GWS for their child was an easy one. However, they expressed some unresolved decisional needs, including a lack of knowledge about certain topics that became relevant and important to them later and a need for more support and resources. Participants also had ongoing informational and psychosocial needs after the single clinical encounter where their decision making occurred. CONCLUSIONS: Participants expressed unmet decisional needs, which may have influenced the quality of their decisions. The strategies that participants suggested may help create parent-tailored education, counseling, decision support, and informed consent processes. CLINICAL RELEVANCE: Health care professionals who offer GWS for children should assess parents' values, priorities, and informational needs and tailor information accordingly. There are opportunities for nurses to become involved in supporting families who are considering GWS for their child.

Comparing the ability of OPTION(12) and OPTION(5) to assess shared decision-making in genetic counselling.

OBJECTIVES: OPTION(12) is the most widely used tool to measure shared decision-making (SDM) in health care. A newer scale, OPTION(5), has been proposed as a more parsimonious measure that better addresses core concepts of SDM. This study compares OPTION(5) to OPTION(12) in prenatal genetic counselling. METHODS: Two raters independently used OPTION(12) and OPTION(5) to score 27 clinical encounters between genetic counsellors (GC) and women with pregnancies at increased risk for genetic conditions. Global and item scores on the two instruments were compared to test concurrent validity and to identify usability in this context. Inter-rater reliability was also assessed for both instruments. RESULTS: Mean scores for OPTION(12) were 43.8 (SD=9.7), and for OPTION(5) were=60.6 (SD=12.5). The correlation between OPTION(12) and OPTION(5) scores was r=0.70. Inter-rater reliability was 0.70 and 0.85 for OPTION(12) and OPTION(5) respectively, however mean inter-rater reliability for individual items was 0.31 and 0.63 for OPTION(12) and OPTION(5) respectively. CONCLUSIONS: GCs exhibit SDM as measured by both OPTION instruments. OPTION(5) exhibits improved psychometric performance relative to OPTION(12), and more specifically targets the core constructs of SDM. However, refinement of OPTION instruments or manuals is needed to improve reliability and validity in GC assessment.

Costs of caring for children with an intellectual developmental disorder.

BACKGROUND: Caring for a child with intellectual developmental disorder (IDD) is expensive for the medical system, for the family, and for society in general. Whereas the health care costs of IDD have been described, the societal and parental costs of IDD have been less well documented. OBJECTIVE: Our goal was to estimate the out-of-pocket costs to parents, and the non-health system costs to society, of raising a child with IDD. METHODS: We used an online retrospective survey, previously developed by our group, to collect parental and societal costs to families of 80 children who presented with IDD of unknown etiology in British Columbia, Canada. RESULTS: Median annual parental costs of caring for 80 children with IDD was CAD$44,570 (range CAD$2245-$225,777). The largest contributors to parental costs were income loss and caregiving time costs. Median annual societal costs (excluding health system costs) were CAD$27,428 (range CAD$0-$119,188). In school age children, the largest contributor to societal costs was a per child school subsidy. Both parental and societal costs increased with increasing IDD severity. Parental costs were not adequately compensated by government benefits received. CONCLUSIONS: Although medical care is universally available through Canadian provincial health systems and social assistance is provided to the families of children with IDD, parents continue to bear a substantial financial burden beyond that associated with raising an unaffected child.

Quantitative associations of scalp and body subcutaneous neurofibromas with internal plexiform tumors in neurofibromatosis 1.

Internal plexiform neurofibromas are a major cause of adverse outcomes in patients with neurofibromatosis 1 (NF1). We investigated the relationship of the numbers of subcutaneous neurofibromas of the scalp or body to internal plexiform tumor volume in 120 NF1 patients who had undergone whole body magnetic resonance imaging (MRI). We identified internal plexiform neurofibromas in 55% of patients, subcutaneous neurofibromas of the body in 75%, and subcutaneous neurofibromas of the scalp in 45%. The number of subcutaneous neurofibromas of the body and scalp were associated with each other (Spearman's Rho = 0.36; P < 0.001). The presence of internal tumors was associated with the presence (odds ratio [OR] = 4.38, 95% confidence interval [CI] 2.04-9.86, P < 0.001) and number (OR = 1.06 per neurofibroma, 95% CI 1.02-1.13, P < 0.001) of subcutaneous neurofibromas of the scalp. The total internal tumor volume was associated with the number of subcutaneous neurofibromas of the body (OR = 1.00086 per neurofibroma, 1.000089-1.0016, P = 0.029) and of the scalp (OR = 1.056 per neurofibroma, 1.029-1.083, P < 0.0001). Numbers of subcutaneous neurofibromas of the scalp and body are associated with internal plexiform tumor burden in NF1. Recognition of these associations may improve clinical management by helping to identify patients who will benefit most from whole body MRI and more intense clinical surveillance.