Ensuring best practice in genomics education: A scoping review of genomics education needs assessments and evaluations.

A health workforce capable of implementing genomic medicine requires effective genomics education. Genomics education interventions developed for health professions over the last two decades, and their impact, are variably described in the literature. To inform an evaluation framework for genomics education, we undertook an exploratory scoping review of published needs assessments for, and/or evaluations of, genomics education interventions for health professionals from 2000 to 2023. We retrieved and screened 4,659 records across the two searches with 363 being selected for full-text review and consideration by an interdisciplinary working group. 104 articles were selected for inclusion in the review-60 needs assessments, 52 genomics education evaluations, and eight describing both. Included articles spanned all years and described education interventions in over 30 countries. Target audiences included medical specialists, nurses/midwives, and/or allied health professionals. Evaluation questions, outcomes, and measures were extracted, categorized, and tabulated to iteratively compare measures across stages of genomics education evaluation: planning (pre-implementation), development and delivery (implementation), and impact (immediate, intermediate, or long-term outcomes). They are presented here along with descriptions of study designs. We document the wide variability in evaluation approaches and terminology used to define measures and note that few articles considered downstream (long-term) outcomes of genomics education interventions. Alongside the evaluation framework for genomics education, results from this scoping review form part of a toolkit to help educators to undertake rigorous genomics evaluation that is fit for purpose and can contribute to the growing evidence base of the contribution of genomics education in implementation strategies for genomic medicine.

Ensuring best practice in genomics education: A theory- and empirically informed evaluation framework.

Implementation of genomic medicine into healthcare requires a workforce educated through effective educational approaches. However, ascertaining the impact of genomics education activities or resources is limited by a lack of evaluation and inconsistent descriptions in the literature. We aim to support those developing genomics education to consider how best to capture evaluation data that demonstrate program outcomes and effectiveness within scope. Here, we present an evaluation framework that is adaptable to multiple settings for use by genomics educators with or without education or evaluation backgrounds. The framework was developed as part of a broader program supporting genomic research translation coordinated by the Australian Genomics consortium. We detail our mixed-methods approach involving an expert workshop, literature review and iterative expert input to reach consensus and synthesis of a new evaluation framework for genomics education. The resulting theory-informed and evidence-based framework encompasses evaluation across all stages of education program development, implementation and reporting, and acknowledges the critical role of stakeholders and the effects of external influences.

Australian Genomics: Outcomes of a 5-year national program to accelerate the integration of genomics in healthcare.

Australian Genomics is a national collaborative partnership of more than 100 organizations piloting a whole-of-system approach to integrating genomics into healthcare, based on federation principles. In the first five years of operation, Australian Genomics has evaluated the outcomes of genomic testing in more than 5,200 individuals across 19 rare disease and cancer flagship studies. Comprehensive analyses of the health economic, policy, ethical, legal, implementation and workforce implications of incorporating genomics in the Australian context have informed evidence-based change in policy and practice, resulting in national government funding and equity of access for a range of genomic tests. Simultaneously, Australian Genomics has built national skills, infrastructure, policy, and data resources to enable effective data sharing to drive discovery research and support improvements in clinical genomic delivery.

Australian public perspectives on genomic newborn screening: which conditions should be included?

BACKGROUND: Implementing genomic sequencing into newborn screening programs allows for significant expansion in the number and scope of conditions detected. We sought to explore public preferences and perspectives on which conditions to include in genomic newborn screening (gNBS). METHODS: We recruited English-speaking members of the Australian public over 18 years of age, using social media, and invited them to participate in online focus groups. RESULTS: Seventy-five members of the public aged 23-72 participated in one of fifteen focus groups. Participants agreed that if prioritisation of conditions was necessary, childhood-onset conditions were more important to include than later-onset conditions. Despite the purpose of the focus groups being to elicit public preferences, participants wanted to defer to others, such as health professionals or those with a lived experience of each condition, to make decisions about which conditions to include. Many participants saw benefit in including conditions with no available treatment. Participants agreed that gNBS should be fully publicly funded. CONCLUSION: How many and which conditions are included in a gNBS program will be a complex decision requiring detailed assessment of benefits and costs alongside public and professional engagement. Our study provides support for implementing gNBS for treatable childhood-onset conditions.

Moving Genomics into the Clinic: Platforms for Implementing Clinical Genomic Data-Sharing in Ways That Address Ethical, Legal and Social Implications.

This section explores the challenges involved in translating genomic research into genomic medicine. A number of priorities have been identified in the Australian National Health Genomics Framework for addressing these challenges. Responsible collection, storage, use and management of genomic data is one of these priorities, and is the primary theme of this section. The recent release of Genomical, an Australian data-sharing platform, is used as a case study to illustrate the type of assistance that can be provided to the health care sector in addressing this priority. The section first describes the National Framework and other drivers involved in the move towards genomic medicine. The section then examines key ethical, legal and social factors at play in genomics, with particular focus on privacy and consent. Finally, the section examines how Genomical is being used to help ensure that the move towards genomic medicine is ethically, legally and socially sound and that it optimises advances in both genomic and information technology.

What's in a name? Justifying terminology for genomic findings beyond the initial test indication: A scoping review.

Genome sequencing can generate findings beyond the initial test indication that may be relevant to a patient or research participant's health. In the decade since the American College of Medical Genetics and Genomics published its recommendations for reporting these findings, consensus regarding terminology has remained elusive and a variety of terms are in use globally. We conducted a scoping review to explore terminology choice and the justifications underlying those choices. Documents were included if they contained a justification for their choice of term(s) related to findings beyond the initial genomic test indication. From 3571 unique documents, 52 were included, just over half of which pertained to the clinical context (n = 29, 56%). We identified four inter-related concepts used to defend or oppose terms: expectedness of the finding, effective communication, relatedness to the original test indication, and how genomic information was generated. A variety of justifications were used to oppose the term "incidental," whereas "secondary" had broader support as a term to describe findings deliberately sought. Terminology choice would benefit from further work to include the views of patients. We contend that clear definitions will improve ethical debate and support communication about genomic findings beyond the initial test indication.

Australian Genomics: A Federated Model for Integrating Genomics into Healthcare.

Australian Genomics is a national collaborative research partnership of more than 80 organizations piloting a whole-of-system approach to integrating genomics into healthcare that is based on federation principles. The aim of Australian Genomics is to assess the application of genomic testing in healthcare at the translational interface between research and clinical delivery, with an emphasis on robust evaluation of outcomes. It encompasses two bodies of work: a research program prospectively providing genomic testing through exemplar clinical projects in rare diseases, cancers, and reproductive carrier screening and interdependent programs for advancing the diagnostic, health informatics, regulatory, ethical, policy, and workforce infrastructure necessary for the integration of genomics into the Australian health system.

Structured approaches to implementation of clinical genomics: A scoping review.

PURPOSE: This study aimed to assess the extent to which structured approaches to implementation of clinical genomics, proposed or adapted, are informed by evidence. METHODS: A systematic approach was used to identify peer-reviewed articles and gray literature to report on 4 research questions: 1. What structured approaches have been proposed to support implementation? 2. To what extent are the structured approaches informed by evidence? 3. How have structured approaches been deployed in the genomic setting? 4. What are the intended outcomes of the structured approaches? RESULTS: A total of 30 unique structured approaches to implementation were reported across 23 peer-reviewed publications and 11 gray literature articles. Most approaches were process models, applied in the preadoption implementation phase, focusing on a "service" outcome. Key findings included a lack of implementation science theory informing the development/implementation of newly designed structured approaches in the genomic setting and a lack of measures to assess implementation effectiveness. CONCLUSION: This scoping review identified a significant number of structured approaches developed to inform the implementation of genomic medicine into clinical practice, with limited use of implementation science to support the process. We recommend the use of existing implementation science theory and the expertise of implementation scientists to inform the design of genomic programs being implemented into clinical care.

Is faster better? An economic evaluation of rapid and ultra-rapid genomic testing in critically ill infants and children.

PURPOSE: To evaluate whether the additional cost of providing increasingly faster genomic results in pediatric critical care is outweighed by reductions in health care costs and increases in personal utility. METHODS: Hospital costs and medical files from a cohort of 40 children were analyzed. The health economic impact of rapid and ultra-rapid genomic testing, with and without early initiation, relative to standard genomic testing was evaluated. RESULTS: Shortening the time to results led to substantial economic and personal benefits. Early initiation of ultra-rapid genomic testing was the most cost-beneficial strategy, leading to a cost saving of AU$26,600 per child tested relative to standard genomic testing and a welfare gain of AU$12,000 per child tested. Implementation of early ultra-rapid testing of critically ill children is expected to lead to an annual cost saving of AU$7.3 million for the Australian health system and an aggregate welfare gain of AU$3.3 million, corresponding to a total net benefit of AU$10.6 million. CONCLUSION: Early initiation of ultra-rapid genomic testing can offer substantial economic and personal benefits. Future implementation of rapid genomic testing programs should focus not only on optimizing the laboratory workflow to achieve a fast turnaround time but also on changing clinical practice to expedite test initiation.

Evaluating the resource implications of different service delivery models for offering additional genomic findings.

PURPOSE: To evaluate the resource implications of different delivery models for the provision of additional findings (AF) in genomics from a health-care purchaser perspective. METHODS: Data from the Additional Findings study were used to develop and validate a discrete event simulation model that represented the pathway of delivering AF. Resource implications were estimated by microcosting the consultations, sample verifications, bioinformatics, curation, and multidisciplinary case review meetings. A proof-of-concept model was used to generate costing, and then the simulation model was varied to assess the impact of an automated analysis pipeline, use of telehealth consultation, full automation with electronic decision support, and prioritizing case review for cases with pathogenic variants. RESULTS: For the proof-of-concept delivery model, the average total cost to report AF was US$430 per patient irrespective of result pathogenicity (95% confidence interval [CI] US$375-US$489). However, the cost of per AF diagnosis was US$4349 (95% CI US$3794-US$4953). Alternative approaches to genetic counseling (telehealth, decision support materials) and to multidisciplinary case review (pathogenic AF cases only) lowered the total per patient cost of AF analysis and reporting by 41-51%. CONCLUSION: Resources required to provide AF can be reduced substantially by implementing alternative approaches to counseling and multidisciplinary case review.

Clinical impact of genomic testing in patients with suspected monogenic kidney disease.

PURPOSE: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. METHODS: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. RESULTS: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). CONCLUSION: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.

Ensuring best practice in genomics education and evaluation: reporting item standards for education and its evaluation in genomics (RISE2 Genomics).

PURPOSE: Widespread, quality genomics education for health professionals is required to create a competent genomic workforce. A lack of standards for reporting genomics education and evaluation limits the evidence base for replication and comparison. We therefore undertook a consensus process to develop a recommended minimum set of information to support consistent reporting of design, development, delivery, and evaluation of genomics education interventions. METHODS: Draft standards were derived from literature (25 items from 21 publications). Thirty-six international experts were purposively recruited for three rounds of a modified Delphi process to reach consensus on relevance, clarity, comprehensiveness, utility, and design. RESULTS: The final standards include 18 items relating to development and delivery of genomics education interventions, 12 relating to evaluation, and 1 on stakeholder engagement. CONCLUSION: These Reporting Item Standards for Education and its Evaluation in Genomics (RISE2 Genomics) are intended to be widely applicable across settings and health professions. Their use by those involved in reporting genomics education interventions and evaluation, as well as adoption by journals and policy makers as the expected standard, will support greater transparency, consistency, and comprehensiveness of reporting. Consequently, the genomics education evidence base will be more robust, enabling high-quality education and evaluation across diverse settings.

Utility of clinical comprehensive genomic characterization for diagnostic categorization in patients presenting with hypocellular bone marrow failure syndromes.

Bone marrow failure (BMF) related to hypoplasia of hematopoietic elements in the bone marrow is a heterogeneous clinical entity with a broad differential diagnosis including both inherited and acquired causes. Accurate diagnostic categorization is critical to optimal patient care and detection of genomic variants in these patients may provide this important diagnostic and prognostic information. We performed real-time, accredited (ISO15189) comprehensive genomic characterization including targeted sequencing and whole exome sequencing in 115 patients with BMF syndrome (median age 24 years, range 3 months - 81 years). In patients with clinical diagnoses of inherited BMF syndromes, acquired BMF syndromes or clinically unclassifiable BMF we detected variants in 52% (12/23), 53% (25/47) and 56% (25/45) respectively. Genomic characterization resulted in a change of diagnosis in 30/115 (26%) including the identification of germline causes for 3/47 and 16/45 cases with pre-test diagnoses of acquired and clinically unclassifiable BMF respectively. The observed clinical impact of accurate diagnostic categorization included choice to perform allogeneic stem cell transplantation, disease-specific targeted treatments, identification of at-risk family members and influence of sibling allogeneic stem cell donor choice. Multiple novel pathogenic variants and copy number changes were identified in our cohort including in TERT, FANCA, RPS7 and SAMD9. Whole exome sequence analysis facilitated the identification of variants in two genes not typically associated with a primary clinical manifestation of BMF but also demonstrated reduced sensitivity for detecting low level acquired variants. In conclusion, genomic characterization can improve diagnostic categorization of patients presenting with hypoplastic BMF syndromes and should be routinely performed in this group of patients.

The expectations and realities of nutrigenomic testing in australia: A qualitative study.

BACKGROUND: Consumer genomic testing for nutrition and wellness, (nutritional genomics), is becoming increasingly popular. Concurrently, health-care practitioners (HPs) working in private practice (including doctors interested in integrative medicine, private genetic counsellors, pharmacists, dieticians, naturopaths and nutritionists) are involved as test facilitators or interpreters. OBJECTIVE: To explore Australian consumers' and HPs' experiences with nutrigenomic testing. METHOD: Semi-structured in-depth interviews were conducted using predominantly purposive sampling. The two data sets were analysed individually, then combined, using a constant comparative, thematic approach. RESULTS: Overall, 45 interviews were conducted with consumers (n = 18) and HPs (n = 27). Many of the consumer interviewees experienced chronic ill-health. Nutrigenomic testing was perceived as empowering and a source of hope for answers. While most made changes to their diet/supplements post-test, self-reported health improvements were small. A positive relationship with their HP appeared to minimize disappointment. HPs' adoption and views of nutrigenomic testing varied. Those enthusiastic about testing saw the possibilities it could offer. However, many felt nutrigenomic testing was not the only 'tool' to utilize when offering health care. DISCUSSION: This research highlights the important role HPs play in consumers' experiences of nutrigenomics. The varied practice suggests relevant HPs require upskilling in this area to at least support their patients/clients, even if nutrigenomic testing is not part of their practice. PATIENT OR PUBLIC CONTRIBUTION: Advisory group included patient/public group representatives who informed study design; focus group participants gave feedback on the survey from which consumer interviewees were sourced. This informed the HP data set design. Interviewees from HP data set assisted with snowball sampling.

Rapid acute care genomics: Challenges and opportunities for genetic counselors.

Genomic medicine in pediatric acute care is showing great promise, with rapid results from exome and genome sequencing returned within days providing critically important information for treatment and management of seriously ill children. Many have suggested that rapid acute care genomics presents novel genetic counseling issues. This is due to the need for rapid response to referrals, the immense emotional distress that parents are likely to experience when their child is in acute care, and the unfamiliar environment of the acute care setting. To explore the practice of genetic counselors in this setting, we conducted qualitative interviews with 16 genetic counselors (GCs), representing a large proportion of GCs at the frontline of providing genetic counseling in acute care settings in Australia. Interviews revealed themes describing genetic counseling in acute care, including practical challenges of counseling within a rapid turnaround time, similarities with other contexts such as prenatal counseling, and the need for education of other health professionals. Interestingly, GCs did not raise concerns in the interviews for parents' ability to provide informed consent for rapid genomic sequencing. GCs also encountered practical and organizational challenges with counseling in this setting where 24-hr care is provided, at odds with traditional '9 to 5' Genetics service delivery. Working closely in a multidisciplinary team was common and participants believed that GCs are well positioned to take a leading role in the education of other health professionals as rapid acute care genomics becomes routine clinical practice. Despite views that genetic counseling practice in rapid acute care genomics is unique, these exploratory data suggest that GCs are flexible, adaptable, and sufficiently skilled to deliver patient-centered counseling in this setting. Our work indicates GCs are ready and willing to contribute at an early stage of adoption of genomic investigations in acute care.

Professional regulation for Australasian genetic counselors.

As a result of the ongoing global expansion of genetic counseling, the need to formalize a system of professional regulation for genetic counselors was identified in Australasia. In June 2017, under the auspices of the Human Genetics Society of Australasia (HGSA), a working party was convened. The purpose of the working party was to provide strategic leadership for the profession of Australasian genetic counselors with a goal to formalize a national regulatory framework for genetic counselors across both Australian and New Zealand jurisdictions. This was ultimately achieved in Australia through full membership with the National Alliance of Self-Regulating Health Professions (NASRHP) while the profession of genetic counseling in New Zealand is utilizing this framework to establish their regulation pathway. Regulation has a number of implications for genetic counselors, their employers, and the wider community, with the primary purpose of regulation being protection of the public from harm. This paper details the process of formalizing self-regulation for genetic counselors in Australasia, by defining professional regulation; outlining the purpose of regulation and the status of regulation for genetic counselors in Australasia and internationally, as well as health professionals more broadly; exploring the challenges of establishing regulation in Australasia; and the next steps for regulation in Australasia. Through detailing this process, the intention is to provide a framework to support genetic counseling colleagues internationally as well as other health professions in Australasia to explore and achieve regulation through their respective jurisdiction.

The leadership behaviors needed to implement clinical genomics at scale: a qualitative study.

PURPOSE: To investigate leadership in clinical genomics and identify likely implications of different leadership approaches for future implementation of clinical genomics. METHODS: We undertook 37 interviews in a cross-sectional qualitative study examining implementation of clinical genomics in Australia. Participants were either nongenetic medical specialists working with genomic initiatives (e.g., immunologists, nephrologists) or working at a service/organizational level (e.g., department heads, chief medical officers). We identified participants as genomic migrants (long-established practitioners) and genomic natives (those medical specialists coming into independent practice with genomic technology in situ). Data were analyzed deductively with reference to leadership approach. RESULTS: Leadership approaches were often blended or reported to iteratively support development of another. There was concern at both the absence or the excess of entrepreneurial leadership (i.e., risk-taking). CONCLUSION: Entrepreneurial leadership is needed to promote innovativeness, risk-taking, and proactivity, essential in these early stages of clinical genomics. Shared decision-making is required from a wide range of clinicians, calling for both clinical and distributed leadership. Sharing leadership, and the potential loss of positional status from formal senior positions, may prove challenging to genomics "migrants," who are essential for nurturing genomic "natives." Clinicians will need support from their organizations and professional bodies to manage the transition.

Exome sequencing in newborns with congenital deafness as a model for genomic newborn screening: the Baby Beyond Hearing project.

PURPOSE: Genomic newborn screening raises practical and ethical issues. Evidence is required to build a framework to introduce this technology safely and effectively. We investigated the choices made by a diverse group of parents with newborns when offered tiered genomic information from exome sequencing. METHODS: This population-derived cohort comprised infants with congenital deafness. Parents were offered exome sequencing and choice regarding the scope of analysis. Options were choice A, diagnostic analysis only; choice B, diagnostic analysis plus childhood-onset diseases with medical actionability; or choice C, diagnostic analysis plus childhood-onset diseases with or without medical actionability. RESULTS: Of the 106 participants, 72 (68%) consented to receive additional findings with 29 (27.4%) selecting choice B and 43 (40.6%) opting for choice C. Family size, ethnicity, and age of infant at time of recruitment were the significant predictors of choice. Parents who opted to have additional findings analysis demonstrated less anxiety and decisional conflict. CONCLUSIONS: These data provide evidence from a culturally diverse population that choice around additional findings is important and the age of the infant when this choice is offered impacts on their decision. We found no evidence that offering different levels of genomic information to parents of newborns has a negative psychological impact.

A cost-effectiveness analysis of genomic sequencing in a prospective versus historical cohort of complex pediatric patients.

PURPOSE: Cost-effectiveness evaluations of first-line genomic sequencing (GS) in the diagnosis of children with genetic conditions are limited by the lack of well-defined comparative cohorts. We sought to evaluate the cost-effectiveness of early GS in pediatric patients with complex monogenic conditions compared with a matched historical cohort. METHODS: Data, including investigation costs, were collected in a prospective cohort of 92 pediatric patients undergoing singleton GS over an 18-month period (2016-2017) with two of the following: a condition with high mortality, multisystem disease involving three or more organs, or severe limitation of daily function. Comparative data were collected in a matched historical cohort who underwent traditional investigations in the years 2012-2013. RESULTS: GS yielded a diagnosis in 42% while traditional investigations yielded a diagnosis in 23% (p = 0.003). A change in management was experienced by 74% of patients diagnosed following GS, compared with 32% diagnosed following traditional investigations. Singleton GS at a cost of AU$3100 resulted in a mean saving per person of AU$3602 (95% confidence interval [CI] AU$2520-4685). Cost savings occurred across all investigation subtypes and were only minimally offset by clinical management costs. CONCLUSION: GS in complex pediatric patients saves significant costs and doubles the diagnostic yield of traditional approaches.

Does genomic sequencing early in the diagnostic trajectory make a difference? A follow-up study of clinical outcomes and cost-effectiveness.

PURPOSE: To systematically investigate the longer-term clinical and health economic impacts of genomic sequencing for rare-disease diagnoses. METHODS: We collected information on continuing diagnostic investigation, changes in management, cascade testing, and parental reproductive outcomes in 80 infants who underwent singleton whole-exome sequencing (WES). RESULTS: The median duration of follow-up following result disclosure was 473 days. Changes in clinical management due to diagnostic WES results led to a cost saving of AU$1,578 per quality-adjusted life year gained, without increased hospital service use. Uninformative WES results contributed to the diagnosis of non-Mendelian conditions in seven infants. Further usual diagnostic investigations in those with ongoing suspicion of a genetic condition yielded no new diagnoses, while WES data reanalysis yielded four. Reanalysis at 18 months was more cost-effective than every 6 months. The parents of diagnosed children had eight more ongoing pregnancies than those without a diagnosis. Taking the costs and benefits of cascade testing and reproductive service use into account, there was an additional cost of AU$8,118 per quality-adjusted life year gained due to genomic sequencing. CONCLUSION: These data strengthen the case for the early use of genomic testing in the diagnostic trajectory, and can guide laboratory policy on periodic WES data reanalysis.