Whole-genome sequencing (WGS) is positioned to become one of the most robust strategies for achieving timely diagnosis of rare genomic diseases. Despite its favorable diagnostic performance compared to conventional testing strategies, routine use and reimbursement of WGS are hampered by inconsistencies in the definition and measurement of clinical utility. For example, what constitutes clinical utility for WGS varies by stakeholder’s perspective (physicians, patients, families, insurance companies, health-care organizations, and society), clinical context (prenatal, pediatric, critical care, adult medicine), and test purpose (diagnosis, screening, treatment selection). A rapidly evolving technology landscape and challenges associated with robust comparative study design in the context of rare disease further impede progress in this area of empiric research. To address this challenge, an expert working group of the Medical Genome Initiative was formed. Following a consensus-based process, we align with a broad definition of clinical utility and propose a conceptually-grounded and empirically-guided measurement toolkit focused on four domains of utility: diagnostic thinking efficacy, therapeutic efficacy, patient outcome efficacy, and societal efficacy. For each domain of utility, we offer specific indicators and measurement strategies. While we focus on diagnostic applications of WGS for rare germline diseases, this toolkit offers a flexible framework for best practices around measuring clinical utility for a range of WGS applications. While we expect this toolkit to evolve over time, it provides a resource for laboratories, clinicians, and researchers looking to characterize the value of WGS beyond the laboratory.

This study systematically reviewed the literature on the impact of digital genetics tools on patient care and system efficiencies. MEDLINE and Embase were searched for articles published between January 2010 and March 2021. Studies evaluating the use of patient-facing digital tools in the context of genetic service delivery were included. Two reviewers screened and extracted patient-reported and system-focused outcomes from each study. Data were synthesised using a descriptive approach. Of 3226 unique studies identified, 87 were included. A total of 70 unique digital tools were identified. As a result of using digital tools, 84% of studies reported a positive outcome in at least one of the following patient outcomes: knowledge, psychosocial well-being, behavioural/management changes, family communication, decision-making or level of engagement. Digital tools improved workflow and efficiency for providers and reduced the amount of time they needed to spend with patients. However, we identified a misalignment between study purpose and patient-reported outcomes measured and a lack of tools that encompass the entire genetic counselling and testing trajectory. Given increased demand for genetic services and the shift towards virtual care, this review provides evidence that digital tools can be used to efficiently deliver patient-centred care. Future research should prioritise development, evaluation and implementation of digital tools that can support the entire patient trajectory across a range of clinical settings. PROSPERO registration numberCRD42020202862.

We sought to understand the experiences of parents/caregivers of children with inherited metabolic diseases (IMD) in order to inform strategies for supporting patients and their families. We investigated their experiences regarding the management of disease, its impact on child and family life, and interactions with the health care system. From four Canadian centres, we conducted semi-structured telephone interviews with parents/caregivers of children with an IMD who were born between 2006 and 2015 and who were participating in a larger cohort study. Participants were selected with the aim of achieving a diverse sample with respect to treatment centre, IMD, and age of the child. Interviews emphasized the impacts of the disease and its treatment on the child and family and explicitly queried perceptions of interactions with the health care system. We identified emergent themes from the interview data. We completed interviews with 21 parents/caregivers. The 21 children were aged <1 to 7 years old with IMD that included amino acid disorders, urea cycle disorders, fatty acid oxidation disorders, and organic acid disorders or ‘other’ IMD. Most parents reported that they and their families had adapted well to their child’s diagnosis. Parents used proactive coping strategies to integrate complex disease management protocols into routine family life. An important source of stress was concern about the social challenges faced by their children. Participants reported positive interactions with their most involved health care providers within the metabolic clinic. However, they reported challenges associated with the health care system outside of disease-specific metabolic care, when encountering systems and providers unfamiliar with the child’s disease. The successful use of proactive coping strategies among parents of children with IMD in this study suggests the potential value of promoting positive coping and is an important direction for future study. Parents’ social concerns for their children were important stressors that warrant consideration by health care providers positioned to support families. Our results with respect to experiences with care highlight the important role of specialized metabolic clinics and point to a need for better coordination of the care that takes place outside the disease-specific management of IMD.

Now more than ever, digital applications are essential to accessing genetics services and optimizing their delivery. At this watershed moment, digital solutions must be balanced with the merits of human interaction, without compromising quality or exacerbating existing genomic and technological disparities. As highlighted by the COVID-19 pandemic, digital solutions are becoming essential for the provision of clinical genetics services. However, as this Comment emphasizes, the use of digital tools alone can exacerbate genomic and technological disparities and must be balanced with the merits of face-to-face interactions.

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.