Introduction Genomic testing allows for the identification of disease-causing genetic variants and may also reveal secondary findings (SF) unrelated to the reason for testing. As the list of medically actionable genes continues to grow, it is important to understand the impact of these findings on clinical care and patient experience, particularly in paediatric settings. This work will generate novel evidence on the clinical, patient, family and system impacts of medically actionable SF generated from genomic testing.Methods and analysis This mixed-methods, prospective, observational study will describe the impacts of SF on clinical care and the patient and family experience. Participants include probands and/or parents of probands who receive SF (ie, cases), clinicians involved in managing their care and controls matched 2:1 to cases based on age group, phenotype and primary genomic testing result. We aim to enrol 50 cases and 100 controls among those who receive genomic testing through Genome-wide Sequencing Ontario or other local sequencing initiatives in Ontario, Canada. Clinicians involved in follow-up care will complete questionnaires related to risk assessment, medical recommendations and clinical utility of SF post-result disclosure and one year later. Patient questionnaires will record health service use and psychological outcomes (ie, personal utility, empowerment) every 6 months for 2 years. These data will be compared between cases and controls using parametric tests. Cases will be invited to a qualitative interview to learn about their experiences. Data will be analysed using quantitative and qualitative techniques, triangulating datasets to enhance the validity and depth of the findings.Ethics and dissemination This study is approved by the Clinical Trials Ontario (CTO) Research Ethics Review System (REB# CTO 3655). We plan to present our results to academic, patient, clinician and decision-maker audiences through articles and presentations at provincial, national and international meetings.

Patient-facing digital tools in genetics can increase efficiency and personalize care, but may threaten patient-provider relationships due to a diminished sense of connection associated with traditional face-to-face encounters. To learn about experiences with and preferences for using digital tools in the delivery of genetic services, semi-structured interviews were conducted with patients or parents of children who had clinical or research genetic testing. Direct experience with a digital healthcare tool was not required for inclusion. Data were analyzed thematically. A total of thirty participants from across Canada were interviewed. Of these, 17 (57%) received genetic testing for themselves and 20 (67%) identified as female. Participants described previous positive experiences with digital tools in medical settings and welcomed the shift towards their increased use in genetics. Participants desired increased agency, access, and control while maintaining the human touch with their healthcare providers. They anticipated that supplementing care with a digital tool could provide the balance and personalization desired for digitally-enabled agency and better access to health information, including genetic test results. Digital tools can facilitate innovation in patient-centered care, enabling a personalized model of care that retains a sense of connection with healthcare providers.

Genomic sequencing (GS) for patients and families with rare disease creates the opportunity for precise diagnosis as well as the option to learn about medically actionable secondary findings (SF). Debate persists internationally on how to manage the analysis and disclosure of SF, especially in settings where service delivery models for GS are still in development and outcomes are preliminary. This study aimed to understand parents' decision to opt-out of learning about their child's SF for adult-onset conditions and whether an SF identified in a child was inherited. All children received GS as part of their diagnostic work-up for a rare disease. Sixteen semistructured interviews were conducted with parents. Guided by a qualitative approach, interviews were analyzed with inductive content analysis. Participants reported that the timing of decision-making, competing priorities, anticipated adverse psychological outcomes, and health-related beliefs and worldviews contributed to their decision to opt-out of receiving SF. An emphasis was placed on a preference for flexible SF delivery models to aid in reducing the burden of SF decision-making at the time of indication-based testing. Genetic service delivery models that separate the timing of decisions about indication-based test results and SF may address patient preferences. Findings from this work may inform clinical practice and policy in jurisdictions where SF delivery models are still being developed and optimized.

PURPOSE:Consensus is lacking on how to define and measure the concept of personal utility in genomic medicine. The study objective was to develop and assess the validity of the Patient-reported Genetic testing Utility InDEx (P-GUIDE) for pediatric genetics. METHODS:Informed by the literature, experts, and patient partners, a 55-item first draft of P-GUIDE was developed. Interviews were conducted with parents of children who had undergone genetic testing to assess item clarity and relevance. Clinical experts assessed content validity. Two independent sequential samples of parents completed questionnaires. Item reduction was achieved using exploratory factor analysis and confirmatory factor analysis. The performance characteristics of the final tool were assessed. RESULTS:Interviewees (n = 22) found most items relevant but requiring modification. Clinical experts (n = 11) recommended further revisions. Exploratory factor analysis (n = 103) removed 9 items. Confirmatory factor analysis (n = 103) generated a final tool consisting of 19 items across 3 factors: understanding and decision-making, psychosocial benefit, and psychosocial concern. P-GUIDE scores were positively correlated with published measures of utility, knowledge, empowerment, and emotion, establishing construct validity. P-GUIDE demonstrated strong test-retest reliability. CONCLUSION:P-GUIDE is available for use in pediatric populations. Emerging adaptations of P-GUIDE contribute to a novel utility measurement system for genetic testing.

BACKGROUND:Assessing clinical utility of genome sequencing (GS) is essential for healthcare decisions. This study quantified the multidimensional utility of GS using the validated Clinician-reported Genetic testing Utility InDEx (C-GUIDE) within a diverse rare disease cohort at the Hong Kong Genome Project. METHODS:Adult and paediatric patients suspected of genetic disorders were recruited from the Hong Kong Children's Hospital. Clinical geneticists evaluated GS utility based on 17 items. Total C-GUIDE utility scores and global item scores were calculated, with individual item scores ranging from -2 to 2. RESULTS:Between March and July 2024, three clinical geneticists completed 247 C-GUIDE ratings for 245 probands, with 25% receiving positive, 7% inconclusive, and 69% negative GS results. Total C-GUIDE scores ranges from -1 to 30, with a mean of 6.1 (SD = 10.0). Multivariate regression analysis indicates that positive GS findings are associated with a 16.9-point increase in C-GUIDE scores compared to inconclusive or negative results (p < 0.001). Notably, the highest mean scores are observed in psychosocial benefits for patients and families, regardless of GS results. The mean global item score, representing overall assessment of clinical utility, is 0.53 (SD = 0.06). Baseline patient characteristics are not independently associated with C-GUIDE scores. CONCLUSIONS:This study represents the first and largest of its kind in the Asia Pacific region, highlighting the multidimensional benefits of GS and the importance of nationwide Genome Projects. By highlighting that clinical utility is primarily influenced by test results rather than patient characteristics, this study underscores the importance of equitable GS implementation across populations.

Purpose Genomic newborn screening (gNBS) is emerging worldwide. Evidence of clinical utility, acceptability, and performance is required to guide policy and funding decisions. We aimed to develop a tool called C-GUIDE NBS, adapted from the Clinician-reported Genetic testing Utility InDEx (C-GUIDE), to quantify the clinical utility of gNBS for diagnostic testing. Methods We drafted an initial version of the tool by identifying relevant domains and modifying existing C-GUIDE items. Interviews were conducted with clinicians involved in gNBS to assess item relevance, comprehensibility, and comprehensiveness. We quantified the number of items that clinicians accepted, modified, or rejected and synthesized qualitative feedback to inform a revised version. These participants also completed content validity questionnaires to rate the relevance and clarity of each item using a 4-point Likert scale. The relevance and clarity scores were calculated between 0 and 1. Then, we refined C-GUIDE NBS using a 3-step international Delphi consensus process. Results In the cognitive interviews, participants (N = 22) indicated that 8 of the preliminary 11 items were acceptable for inclusion as is; 2 items required modifications, and 1 was rejected. On the revised 10-item tool, item relevance and clarity scores <0.8 prompted further revision in preparation for the consensus process. In the next step, which involved a Delphi panel, 2 rounds of surveys and 2 consensus meetings with 26 new experts led to the generation of a final 7-item tool. Conclusion Once validated, the C-GUIDE NBS will offer an expert-informed measurement strategy for capturing the clinical utility of gNBS. Following validity testing, the C-GUIDE NBS will be available for licensed use.

Digital tools have emerged as a promising solution to increase the efficiency and capacity of genomic services. However, accessing information through internet-based applications raises concerns about privacy and security risks. As patient-facing digital tools are developed for genomic medicine, it is vital to understand and incorporate patients' perspectives on digital privacy and security. A qualitative study was conducted using semi-structured interviews and interpretive description. Thirty participants who previously received genetic testing for themselves (n = 17) or their child (n = 13) were interviewed (n = 20 females, n = 15 above 50 years old). Participants were willing to store and access genomics personal health information (PHI) in a patient-facing digital platform. The main benefit identified by participants was the ability to access and control their own PHI. Participants expressed that the benefits of digital genomics services, such as patient empowerment and personalized care, outweighed the perceived risks, such as potential data leaks. In order to minimize risks, participants emphasized the importance of transparency about the security measures in place and who would have access to their PHI. These findings inform the design of digital genomic platforms to enhance patients' sense of security, which is critical for the uptake and usage of any platform.

PURPOSE:Use of genomic sequencing (GS) in neonatal intensive care units (NICUs) has increased with improved diagnostic yield. However, uncertainty persists regarding when and for whom GS is most useful. Because a standardized approach to assessing utility is lacking, we developed a novel version of the Clinician-reported Genetic testing Utility InDEx (C-GUIDE) to quantify the utility of GS in NICUs. METHODS:Informed by a scoping review, we developed a draft C-GUIDE NICU tool to quantify utility, which underwent iterative revisions through feedback from clinician interviews and questionnaires on item relevance, comprehensibility, and comprehensiveness. We finalized the expert-informed C-GUIDE NICU using an international Delphi consensus process. RESULTS:Scoping review (n = 25 articles) and interviews (n = 21) revealed key themes of utility. Guided by qualitative feedback and item scoring, C-GUIDE was iteratively reduced to include 21, 18, and 14 items. The Delphi consensus process with 22 experts achieved item consensus and stability, yielding a final 10-item tool. CONCLUSION:Using a rigorous process, we developed a consensus-based standardized method for capturing the clinical utility of GS in NICUs. C-GUIDE NICU can be used by clinicians, researchers, and payers to assess GS value to patient care and will be available for licensed use following reliability and validity testing.

Purpose:Evidence of personal utility of genetic testing is critical to clinical care, funding, and policy decisions. We aimed to understand how patient-oriented values and preferences for genetic testing vary across clinical settings to inform the development of a personal utility index. Methods:Participants were recruited from 3 clinical settings: pediatric clinical genetics, pediatric oncology, and prenatal care. For each cohort, a preliminary set of domains and elements of utility were generated from the literature. Semi-structured interviews were conducted with parents to understand the meaning of personal utility and relevance of preliminary domains and elements. Deductive coding identified shared and unique elements of utility across cohorts. Results:A total of 63 parents were interviewed. Personal utility domains that resonated with participants included cognitive, medical management, affective, behavioral, and social. Common elements included increased understanding about the cause of their child's condition and contributing to scientific knowledge. Unique elements were identified in each cohort: identifying support services in clinical genetics, understanding cancer risks in oncology, and pregnancy decision making in prenatal care. Conclusion:We identified shared and unique elements of personal utility across cohorts from 3 clinical settings, suggesting the need to tailor utility assessment to the clinical setting and patient population.

Clinical genetic services address diverse genetic testing needs, but there is no comprehensive digital solution to meet this variety. We aimed to develop and test the usability of the Genetics Navigator (GN), a platform designed to enhance genetic services for paediatric and adult patients. The GN prototype was created with input from a patient and clinician advisory board, informed by prior research. Usability testing involved genetics patients (N = 14), parents of paediatric patients (N = 4), and the general public (N = 10). Participants provided feedback using the ‘think aloud’ method when using the platform. We used the System Usability Scale (SUS) for quantitative evaluation. Qualitative data were coded by platform section, item, and identified key areas for improvement. Building on the Genetics Adviser platform, we added video and written content for various genetic conditions and patient groups, including pre-test education, counselling, decision support, history collection, post-test result disclosure, and management. Key feedback during rounds of usability testing emphasized the need for a supportive design, seamless workflow, and engaging experience of the tool. The tool was modified to reflect the feedback, and the GN achieved an average SUS score of 87.7 ± 10.9 (N = 28), indicating above-average usability. Future research will evaluate its clinical and cost-effectiveness in a randomized trial.

Introduction Type 1 diabetes is a chronic autoimmune disease that often presents with diabetic ketoacidosis at diagnosis. Since detection of type 1 diabetes risk is possible using genetic risk scores and autoantibody assays, prevention of diabetic ketoacidosis or delayed onset of type 1 diabetes may be possible and may improve outcomes. Several pilot screening programmes for type 1 diabetes risk have emerged worldwide but outcomes measured in these screening programmes are heterogeneous, making it difficult to compare and synthesise findings across studies. To improve the standardisation of outcome reporting and measurement, we aim to develop a patient-oriented core outcome set for studies of type 1 diabetes risk screening.Methods and analysis This five-step protocol was developed in alignment with the COS-STAndardised Protocol Statement and the Core Outcome Measures in Effectiveness Trials framework. The five steps will include: (1a) conducting a rapid literature review, (1b) gathering input on candidate outcomes from members of the public, (2) combining literature and public input to prepare a preliminary list of outcomes, (3) conducting Delphi surveys with a range of stakeholders to begin to establish consensus on outcomes, (4) holding a final consensus meeting to establish consensus on outcomes and (5) establishing the outcome measurement instruments for the core outcome set.Ethics and dissemination Ethics approval has been provided by The Hospital for Sick Children Research Ethics Board. The core outcome set will be distributed to researchers and clinicians involved in diabetes screening and clinical care, patient and family networks, research funders, journal editors, public health experts, and policymakers. Disseminated materials will be tailored to the various end users in the form of publication through academic journals, policy briefs, conferences, educational webinars, websites and social media.

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 ef fi ciency 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, ef fi ciency, and quality of care in genetics practice. Successful use of digital tools in practice will require careful consideration of their potential unintended impacts. (c) 2024 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.

Strategies for improving the capacity and efficiency of genetic service delivery are vital in supporting genetic healthcare providers while maintaining patient satisfaction. Patient-facing digital tools, which support clinicians in scaling genetic testing services, are transforming clinical genetic services by enhancing accessibility, engagement, and personalized care for patients. However, digital health tools are often siloed in their application and therefore only support specific components of genetic service delivery and/or only support specific patient populations.