CONTEXT The greatest public health benefit of advances in understanding the human genome may be realized for common chronic diseases such as cardiovascular disease, diabetes mellitus, and cancer. ...Attempts to integrate such knowledge into clinical practice are still in the early stages, and as a result, many questions surround the current state of this translation. OBJECTIVE To synthesize current information on genetic health services for common adult-onset conditions by examining studies that have addressed the outcomes, consumer information needs, delivery, and challenges in integrating these services. DATA SOURCES MEDLINE articles published between January 2000 and February 2008. STUDY SELECTION Original research articles and systematic reviews dealing with common chronic adult-onset conditions were reviewed. A total of 3371 citations were reviewed, 170 articles retrieved, and 68 articles included in the analysis. DATA EXTRACTION Data were independently extracted by one reviewer and checked by another with disagreement resolved by consensus. Variables assessed included study design and 4 key areas: outcomes of genomic medicine, consumer information needs, delivery of genomic medicine, and challenges and barriers to integration of genomic medicine. DATA SYNTHESIS Sixty-eight articles contributed data to the synthesis: 5 systematic reviews, 8 experimental studies, 35 surveys, 7 pre/post studies, 3 observational studies, and 10 qualitative reports. Three systematic reviews, 4 experimental studies, and 9 additional studies reported on outcomes of genetic services. Generally there were modest positive effects on psychological outcomes such as worry and anxiety, behavioral outcomes have shown mixed results, and clinical outcomes were less well studied. One systematic review, 1 randomized controlled trial, and 14 other studies assessed consumer information needs and found in general that genetics knowledge was reported to be low but that attitudes were generally positive. Three randomized controlled trials and 13 other studies assessed how genomic medicine is delivered and newer models of delivery. One systematic review and 19 other studies assessed barriers; the most consistent finding was the self-assessed inadequacy of the primary care workforce to deliver genetic services. Additional identified barriers included lack of oversight of genetic testing and concerns about privacy and discrimination. CONCLUSION Many gaps in knowledge about organization, clinician, and patient needs must be filled to translate basic and clinical science advances in genomics of common chronic diseases into practice.
Exome and genome sequencing (ES/GS) are performed frequently in patients with congenital anomalies, developmental delay, or intellectual disability (CA/DD/ID), but the impact of results from ES/GS on ...clinical management and patient outcomes is not well characterized. A systematic evidence review (SER) can support future evidence-based guideline development for use of ES/GS in this patient population.
We undertook an SER to identify primary literature from January 2007 to March 2019 describing health, clinical, reproductive, and psychosocial outcomes resulting from ES/GS in patients with CA/DD/ID. A narrative synthesis of results was performed.
We retrieved 2654 publications for full-text review from 7178 articles. Only 167 articles met our inclusion criteria, and these were primarily case reports or small case series of fewer than 20 patients. The most frequently reported outcomes from ES/GS were changes to clinical management or reproductive decision-making. Two studies reported on the reduction of mortality or morbidity or impact on quality of life following ES/GS.
There is evidence that ES/GS for patients with CA/DD/ID informs clinical and reproductive decision-making, which could lead to improved outcomes for patients and their family members. Further research is needed to generate evidence regarding health outcomes to inform robust guidelines regarding ES/GS in the care of patients with CA/DD/ID.
Genetic tests have become widely available. We sought to understand the use of genetic tests in the practice of frontline clinicians within the United States Department of Veterans Affairs (VA).
We ...administered a web-based survey to clinicians at 20 VA facilities. Physicians, nurse practitioners, physician assistants, and pharmacists were eligible. We excluded genetics providers and clinicians not seeing patients. We used multiple logistic regression to evaluate the associations between clinician characteristics and experience with genetics.
The response rate was 11.3% (1207/10,680) and of these, 909 respondents were eligible. Only 20.8% of the respondents reported feeling prepared to use genetic tests and 13.0% of the respondents were currently ordering genetic tests; although, it was usually only 1 or 2 a year. Delivery of genetic tests without involving genetics providers was preferred by only 7.9% of the respondents. Characteristics positively associated with currently ordering genetic tests included practice in clinical and research settings, believing improving genetics knowledge could alter their practice, feeling prepared to use genetic tests, and referral of at least 1 patient to genetics in the past year.
Most VA clinicians don’t feel prepared to use genetic tests. Those with genetic testing experience are more likely to consult genetics providers. The demand for genetics providers should increase as frontline clinicians use genetic tests in their practice.
To determine whether family history of coronary heart disease (FH) definitions differ in their association with atherosclerotic cardiovascular disease (ASCVD) events.
Participants who provided FH ...data from July 17, 2000, through February 24, 2004, were identified. Definitions of FH were any, premature, and Familial Risk Assessment (FRA). Outcomes included coronary heart disease (CHD), stroke, peripheral artery disease, angina, and congestive heart failure. Multivariable-adjusted Cox models examined the association of FH definitions with events. C statistics and the net reclassification index examined the incremental prognostic contribution of each definition.
In 6200 participants, the proportions of any FH and premature FH were 36% and 16%, respectively, and of weak, moderate, and strong familial risk were 20%, 16%, and 20%, respectively. Over median follow-up of 10.1 years (range, 0.02-11.5 years), 741 participants experienced a composite event. Compared with no FH, any FH was associated with incident CHD, angina, and composite ASCVD (hazard ratios 95% CIs: 1.4 1.1-1.8, 1.6 1.2-2.1, and 1.3 1.1-1.5, respectively). Similar results were obtained for premature FH compared with no FH and for strong compared with weak FRA for these 3 outcomes. There was no association between the FH definitions and noncoronary cardiovascular events. Compared with traditional risk factors (C statistic = 0.740), any FH, premature FH, and FRA all improved discrimination of composite ASCVD (all P < .01); however, the differences in C statistics among any FH (0.743), premature FH (0.742), and FRA (0.744) were numerically small, as were differences in the net reclassification index.
A single question regarding the presence of FH in any first-degree relative performs just as well as more complicated assessments in predicting CHD.
clinicaltrials.gov Identifier: NCT00005487.
Germline testing laboratories have evolved over several decades. We describe laboratory business models and practices and explore their implications on germline testing availability and access.
We ...conducted semistructured interviews with key informants using purposive sampling. We interviewed 13 key informants representing 14 laboratories. We used triangulation and iterative data analysis to identify topics concerning laboratory business models and practices.
We characterized laboratories as full-service (FSL), for-profit germline (PGL), and not-for-profit germline (NGL). Relying on existing payer contracts is a key characteristic of the FSL business models. FSLs focus on high-volume germline tests with evidence of clinical utility that have reimbursable codes. In comparison, a key business model characteristic of PGLs is direct patient billing facilitated by commodity-based pricing made possible by investors and industry partnerships. Client billing is a key business model characteristic of NGLs. Because many NGLs exist within academic settings, they are challenged by their inability to optimize laboratory processes and billing practices.
Continued availability of, and access to germline testing will depend on the financial success of laboratories; organizational characteristics of laboratories and payers; cultural factors, particularly consumer interest and trust; and societal factors, such as regulation and laws surrounding pricing and reimbursement.
The aim of this study was to survey American College of Medical Genetics and Genomics members about secondary findings from clinical genome-scale sequencing.
A Web-based survey was mailed to 1,687 ...members of the American College of Medical Genetics and Genomics. Exploratory factor analysis identified underlying factors assessed by survey items. Linear regression assessed associations between factor scores and respondent characteristics.
The response rate was 29%. Four factors explained 51% of the survey variance: best practices, patient preferences, guidance, and informed consent. Most agreed with "best practice" items describing seeking and reporting of secondary findings as consistent with medical standards, having sufficient evidence, and, for adults, the benefits generally outweighing potential harms. There was lack of agreement regarding benefits versus harms for children and impact on health-care resources. The majority agreed that patient preferences should be considered, including ability to opt out, and that informed consent was feasible and critical. Characteristics significantly associated with factor scores included country of residence, sequencing experience, and years in practice.
The American College of Medical Genetics and Genomics should update a list of genes to be assessed when clinical genome-scale sequencing is performed. Informed consent is necessary, and reporting of secondary findings should be optional. Research on implementation of secondary findings reporting is needed.
The landscape of payment for genetic testing has been changing, with an increase in the number of laboratories offering testing, larger panel offerings, and lower prices. To determine the influence ...of payer coverage and out‐of‐pocket costs on the ordering of NGS panel tests for hereditary cancer in diverse settings, we conducted semi‐structured interviews with providers who conduct genetic counseling and order next‐generation sequencing (NGS) panels purposefully recruited from 11 safety‐net clinics and academic medical centers (AMCs) in California and North Carolina, states with diverse populations and divergent Medicaid expansion policies. Thematic analysis was done to identify themes related to the impact of reimbursement and out‐of‐pocket expenses on test ordering. Specific focus was put on differences between settings. Respondents from both safety‐net clinics and AMCs reported that they are increasingly ordering panels instead of single‐gene tests, and tests were ordered primarily from a few commercial laboratories. Surprisingly, safety‐net clinics reported few barriers to testing related to cost, largely due to laboratory assistance with prior authorization requests and patient payment assistance programs that result in little to no patient out‐of‐pocket expenses. AMCs reported greater challenges navigating insurance issues, particularly prior authorization. Both groups cited non‐coverage of genetic counseling as a major barrier to testing. Difficulty of access to cascade testing, particularly for family members that do not live in the United States, was also of concern. Long‐term sustainability of laboratory payment assistance programs was a major concern; safety‐net clinics were particularly concerned about access to testing without such programs. There were few differences between states. In conclusion, the use of laboratories with payment assistance programs reduces barriers to NGS panel testing among diverse populations. Such programs represent a major change to the financing and affordability of genetic testing. However, access to genetic counseling is a barrier and must be addressed to ensure equity in testing.
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