Daniel Assamad

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.

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.

Introduction Genetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings. Methods and analysis We will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives. Ethics and dissemination This study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals. Trial registration number NCT06455384.

In genomics, perceived and personal utility have been proposed as constructs of value that include the subjective meanings and uses of genetic testing. Precisely what constitutes these constructs of utility and how they vary by stakeholder perspective remains unresolved. To advance methods for measuring the value of genetic testing in child health, we conducted a scoping review of the literature to characterize utility from the perspective of parents/caregivers. Peer reviewed literature that included empiric findings from parents/caregivers who received genetic test results for an index child and was written in English from 2016–2020 was included. Identified concepts of utility were coded according to Kohler’s construct of personal utility. Of 2142 abstracts screened, 33 met inclusion criteria. Studies reflected a range of genetic test types; the majority of testing was pursued for children with developmental or neurodevelopmental concerns. Coding resulted in 15 elements of utility that mapped to Kohler’s four domains of personal utility (affective, cognitive, behavioural and social) and one additional medical management domain. An adapted construct of utility for parents/caregivers may enable specific and standardized strategies for researchers to use to generate evidence of the post-test value of genetic testing. In turn, this will contribute to emerging methods for health technology assessment and policy decision making for genomics in child health.