Workforce Implications of Increased Referrals to Hereditary Cancer Services in Canada: A Scenario-Based Analysis.

Over the last decade, utilization of clinical genetics services has grown rapidly, putting increasing pressure on the workforce available to deliver genetic healthcare. To highlight the policy challenges facing Canadian health systems, a needs-based workforce requirements model was developed to determine the number of Canadian patients in 2030 for whom an assessment of hereditary cancer risk would be indicated according to current standards and the numbers of genetic counsellors, clinical geneticists and other physicians with expertise in genetics needed to provide care under a diverse set of scenarios. Our model projects that by 2030, a total of 90 specialist physicians and 326 genetic counsellors (1.7-fold and 1.6-fold increases from 2020, respectively) will be required to provide Canadians with indicated hereditary cancer services if current growth trends and care models remain unchanged. However, if the expansion in eligibility for hereditary cancer assessment accelerates, the need for healthcare providers with expertise in genetics would increase dramatically unless alternative care models are widely adopted. Increasing capacity through service delivery innovation, as well as mainstreaming of cancer genetics care, will be critical to Canadian health systems' ability to meet this challenge.

Defining Need Amid Exponential Change: Conceptual Challenges in Workforce Planning for Clinical Genetic Services.

Rapid growth in the volume of referrals to clinical genetics services in many countries during the past 15 years makes workforce planning a critical policy tool in ensuring that the capacity of the clinical genetics workforce is large enough to meet current and future needs. This article explores the distinctive challenges of workforce planning in clinical genetics and provides recommendations for addressing these challenges using a needs-based planning approach. Specifically, at least 3 features complicate efforts to estimate the need for clinical genetic services: the difficulty in linking many clinical genetic services to concrete health outcomes; the rapidly changing nature of genetic medicine, which creates intrinsic uncertainty about the appropriate level of service; and the heightened relevance of patient preferences in this context. Our recommendations call for needs-based planning studies to include an explicit definition of necessary care, to be flexible in considering nonhealth benefits, to err on the side of including services currently funded by health systems even when evidence about outcomes is limited, and to use scenario analysis and expert input to explore the impact of uncertainty about patients' preferences and future technologies on estimates of workforce requirements.

A Rapid Review on the Value of Biobanks Containing Genetic Information.

OBJECTIVES: Increasing access to health data through biobanks containing genetic information has the potential to expand the knowledge base and thereby improve screening, diagnosis, and treatment options for many diseases. Nevertheless, although privacy concerns and risks surrounding genetic data sharing are well documented, direct evidence in favor of the hypothesized benefits of data integration is scarce, which complicates decision making in this area. Therefore, the objective of this study is to summarize the available evidence on the research and clinical impacts of biobanks containing genetic information, so as to better understand how to quantify the value of expanding genomic data access. METHODS: Using a rapid review methodology, we performed a search of MEDLINE/PubMed and Embase databases; and websites of biobanks and genomic initiatives published from 2010 to 2022. We classified findings into 11 indicators including outputs (a direct product of the biobank activities) and outcomes (changes in scientific and clinical capacity). RESULTS: Of 8479 abstracts and 101 gray literature sources were reviewed, 96 records were included. Although most records did not report key indicators systematically, the available evidence concentrated on research indicators such as publications and gene-disorder association discoveries (63% of studies), followed by research infrastructure (26%), and clinical indicators (11%) such as supporting the diagnosis of individual patients. CONCLUSIONS: Existing evidence on the benefits of biobanks is skewed toward easily quantifiable research outputs. Measuring a comprehensive set of outputs and outcomes inspired by value frameworks is necessary to generate better evidence on the benefits of genomic data sharing.

Using Rasch measurement theory to explore the fitness for purpose of the genetic counseling outcome scale: a tale of two scales.

BACKGROUND: The genetic counseling outcome scale (GCOS-24) is commonly used in clinical genetics to measure patient empowerment; however, there is inconclusive psychometric evidence about this scale. METHODS: Using data from an urban Canadian clinic where the GCOS-24 is routinely administered before (T1) and 1 month after (T2) genetic counseling, we used Rasch measurement theory (RMT) to test the ordering of response option thresholds, fit, spread of item locations, residual correlations, person separation index (PSI), and stability across time. RESULTS: Data from 379 participants showed that the original GCOS-24 items had poor fit to the Rasch model (χ2 = 367.8, p < 0.001). Two models emerged that demonstrated excellent fit to the Rasch model. In Model 1, the response scale options were collapsed and 8 items were removed, leading to an excellent fit to the Rasch model (χ2 = 112.4, df = 144, p = 0.975), good reliability (rp = 0.82), and responsiveness to change (mean = 0.75 logits, F = 125.68, p < 0.001). In Model 2, the response scale options were collapsed, 3 items were removed, and the scale divided into two sets (GCOS-Pos, GCOS-Neg). The GCOS-Pos set showed excellent overall fit to the Rasch model (χ2 = 92.5, df = 90, p = 0.407), good reliability (rp = 0.73), and responsiveness to change (mean = 0.74 logits, F = 80.12, p < 0.001). The GCOS-Neg set showed excellent overall fit to the Rasch model (χ2 = 84.55, df = 97, p = 0.81), but poor reliability (rp = 0.19) and small, but significant responsiveness to change (mean = 0.19 logits, F = 28.73, p < 0.001). CONCLUSION: These models show that there are psychometric issues with the GCOS-24 scale, and our study provides options for how to measure empowerment more robustly.

A qualitative study exploring the consumer experience of receiving self-initiated polygenic risk scores from a third-party website.

The number of people accessing their own polygenic risk scores (PRSs) online is rapidly increasing, yet little is known about why people are doing this, how they react to the information, and what they do with it. We conducted a qualitative interview-based study with people who pursued PRSs through Impute.me, to explore their motivations for seeking PRS information, their emotional reactions, and actions taken in response to their results. Using interpretive description, we developed a theoretical model describing the experience of receiving PRSs in a direct-to-consumer (DTC) context. Dissatisfaction with healthcare was an important motivator for seeking PRS information. Participants described having medical concerns dismissed and experiencing medical distrust, which drove them to self-advocate for their health, which ultimately led them to seek PRSs. Polygenic risk scores were often empowering for participants but could be distressing when PRS information did not align with participants' perceptions of their personal or family histories. Behavioural changes made in response to PRS results included dietary modifications, changes in vitamin supplementation and talk-based therapy. Our data provides the first qualitative insight into how people's lived experience influence their interactions with DTC PRSs.

Where is genetic medicine headed? Exploring the perspectives of Canadian genetic professionals on future trends using the Delphi method.

Driven by technological and scientific advances, the landscape of genetic medicine is rapidly changing, which complicates strategic planning and decision-making in this area. To address this uncertainty, we sought to understand genetic professionals' opinions about the future of clinical genetic and genomic services in Canada. We used the Delphi method to survey Canadian genetic professionals about their perspectives on whether scenarios about changes in service delivery and the use of genomic testing would be broadly implemented in their jurisdiction by 2030. We conducted two survey rounds; the response rates were 32% (27/84) and 67% (18/27), respectively. The most likely scenario was the universal use of noninvasive prenatal screening. The least likely scenarios involved population-based genome-wide sequencing for unaffected individuals. Overall, the scenarios perceived as most likely were those that have existing evidence about their benefit and potential medical necessity, whereas scenarios were seen as unlikely if they involved emerging technologies. Participants expected that the need for genetic healthcare services would increase by 2030 owing to changes in clinical guidelines and increased use of genome-wide sequencing. This study highlights the uncertainty in the future of genetic and genomic service provision and contributes evidence that could be used to inform strategic planning in clinical genetics.

Why do people seek out polygenic risk scores for complex disorders, and how do they understand and react to results?

We sought to explore individuals' motivations for using their direct-to-consumer genetic testing data to generate polygenic risk scores (PRSs) using a not-for-profit third-party tool, and to assess understanding of, and reaction to their results. Using a cross-sectional design, users of Impute.me who had already accessed PRS results were invited to complete an online questionnaire asking about demographics, motivations for seeking PRSs, understanding and interpretation of PRSs, and two validated scales regarding reactions to results-the Impact of Event Scale Revised (IES-R) and the Feelings About genomiC Testing Results (FACToR). Independent samples T-tests and ANOVA were used to explore associations between the variables. 227 individuals participated in the study. The most frequently reported motivation was general curiosity (98.2%). Only 25.6% of participants correctly answered all questions assessing understanding/interpretation of PRSs. Over half of participants (60.8%) experienced a negative reaction (upset, anxious, and/or sad on FACToR scale) after receiving their PRSs and 5.3% scored over the threshold for potential post-traumatic stress disorder on the IES-R. Lower understanding about PRS was associated with experiencing a negative psychological reaction (P values <0.001). Higher quality pre-test information, particularly to improve understanding, and manage expectations for PRS may be useful in limiting negative psychological reactions.

Genetic counseling research and COVID-19: A lesson in resiliency.

GenCOUNSEL is the largest genetic counseling research grant awarded to date and brings together experts in genetic counseling, genomics, law and policy, health services implementation, and health economics research. It is the first project of its kind to examine the genetic counseling issues associated with the clinical implementation of genome-wide sequencing (exome and genome sequencing). GenCOUNSEL is a Canadian-based, multi-method research study that takes place over a variety of sites, including non-clinical, clinical, and laboratory research sites and includes the training of undergraduate and graduate students. The COVID-19 pandemic will likely have a lasting impact on genetic counseling service delivery, research, and training. Almost every aspect of the GenCOUNSEL research project has been impacted by the COVID-19 pandemic. Here we describe how our research recruitment strategies, methods, resource allocation, and training capacity have been affected. We discuss ways that we have adapted to the pandemic including revision of our research methods and work to understand the barriers in order to optimize opportunities. We finish with take-home messages to fellow researchers highlighting the importance of resiliency in genetic counseling research.

Economic Evidence on Potentially Curative Gene Therapy Products: A Systematic Literature Review.

OBJECTIVE: The aim of this review was to summarize all available evidence on the cost effectiveness of potentially curative gene therapies and identify challenges that economic evaluations face in this area. METHODS: We conducted a systematic review of four databases (PubMed/MEDLINE, Embase, CINAHL, EconLit) and grey literature sources. We conducted the search on August 23, 2019 and updated it on November 26, 2020. We included all English, French and Spanish language studies that addressed a gene therapy that had received regulatory approval or had entered a phase III trial, and also reported on costs related to the therapy. Critical appraisal was conducted to assess quality of reporting in included studies. RESULTS: Fifty-six studies were identified. Of the 42 full economic evaluations, 71% (n = 30) evaluated chimeric antigen receptor T-cell therapies, most used either a Markov model (n = 17, 40%) and/or a partitioned survival model (n = 17, 40%), and 76% (n = 32) adopted a public or private payer perspective. The model characteristics with the greatest impact on cost effectiveness included assumptions about the efficacy of the treatment and the comparators used. CONCLUSION: All gene therapies in this review were shown to be more effective than their comparators, although due to high costs not all were considered cost effective at standard cost-effectiveness thresholds. Despite their high cost, some gene therapies have the potential to dominate the alternatives in conditions with high mortality/disability. The choice of comparator and assumptions regarding long-term effectiveness had substantial impacts on cost-effectiveness estimates and need to be carefully considered. Both the quality of inputs and the quality of reporting were highly variable.

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.

Peripheral chemoreceptor deactivation attenuates the sympathetic response to glucose ingestion.

Acute increases in blood glucose are associated with heightened muscle sympathetic nerve activity (MSNA). Animal studies have implicated a role for peripheral chemoreceptors in this response, but this has not been examined in humans. Heart rate, cardiac output (CO), mean arterial pressure, total peripheral conductance, and blood glucose concentrations were collected in 11 participants. MSNA was recorded in a subset of 5 participants via microneurography. Participants came to the lab on 2 separate days (i.e., 1 control and 1 experimental day). On both days, participants ingested 75 g of glucose following baseline measurements. On the experimental day, participants breathed 100% oxygen for 3 min at baseline and again at 20, 40, and 60 min after glucose ingestion to deactivate peripheral chemoreceptors. Supplemental oxygen was not given to participants on the control day. There was a main effect of time on blood glucose (P < 0.001), heart rate (P < 0.001), CO (P < 0.001), sympathetic burst frequency (P < 0.001), burst incidence (P = 0.01), and total MSNA (P = 0.001) for both days. Blood glucose concentrations and burst frequency were positively correlated on the control day (r = 0.42; P = 0.03) and experimental day (r = 0.62; P = 0.003). There was a time × condition interaction (i.e., normoxia vs. hyperoxia) on burst frequency, in which hyperoxia significantly blunted burst frequency at 20 and 60 min after glucose ingestion only. Given that hyperoxia blunted burst frequency only during hyperglycemia, our results suggest that the peripheral chemoreceptors are involved in activating MSNA after glucose ingestion.

Extreme pregnancy: maternal physical activity at Everest Base Camp.

High-altitude natives employ numerous physiological strategies to survive and reproduce. However, the concomitant influence of altitude and physical activity during pregnancy has not been studied above 3,700 m. We report a case of physical activity, sleep behavior, and physiological measurements on a 28-yr-old third-trimester pregnant native highlander (Sherpa) during ascent from 3,440 m to Everest Base Camp (~5,300 m) over 8 days in the Nepal Himalaya and again ~10 mo postpartum during a similar ascent profile. The participant engaged in 250-300 min of moderate to vigorous physical activity per day during ascent to altitude while pregnant, with similar volumes of moderate to vigorous physical activity while postpartum. There were no apparent maternal, fetal, or neonatal complications related to the superimposition of the large volumes of physical activity at altitude. This report demonstrates a rare description of physical activity and ascent to high altitude during pregnancy and points to novel questions regarding the superimposition of pregnancy, altitude, and physical activity in high-altitude natives.

Intra-individual variability in cerebrovascular and respiratory chemosensitivity: Can we characterize a chemoreflex "reactivity profile"?

Intra-individual variability in the magnitude of human cerebrovascular and respiratory chemoreflex responses is largely unexplored. By comparing response magnitudes of cerebrovascular CO2 reactivity (CVR; middle and posterior cerebral arteries; MCA, PCA), central (CCR; CO2) and peripheral respiratory chemoreflexes (PCR; CO2 and O2), we tested the hypothesis that a within-individual reactivity magnitude profile could be characterized. The magnitudes of CVR and CCR were tested with hyperoxic rebreathing and PCR magnitudes were tested through transient respiratory tests (TT-CO2, hypercapnia; TT-N2, hypoxia). No significant intra-individual relationships were found between CCR vs. CVR (MCA and PCA), CCR vs. PCR (TT-N2 or TT-CO2) (r<0.2, P>0.3) response magnitudes. Statistically significant relationships were found between MCA vs. PCA reactivity (r=0.45, P<0.01) and PCR TT-N2 vs. PCR TT-CO2 (r=0.79, P<0.001) responses. Using qualitative and quantitative comparisons, we conclude that an intra-individual chemoreflex reactivity magnitude profile cannot be characterized. These data highlight the considerable between- and within-individual variability that exists in human cerebrovascular and respiratory chemoreflexes.