Clinical implementation of genetic testing in medicine: a US regulatory science perspective

Genetic medicine is one of the key components of personalized medicine, but adoption in clinical practice is still limited. To understand potential barriers and provider attitudes, we surveyed 285 physicians from five Implementing GeNomics In pracTicE (IGNITE) sites about their perceptions as to the clinical utility of genetic data as well as their preparedness to integrate it into practice. These responses were also analyzed in comparison to the type of study occurring at the physicians’ institution (pharmacogenetics versus disease genetics). The majority believed that genetic testing is clinically useful; however, only a third believed that they had obtained adequate training to care for genetically “high-risk” patients. Physicians involved in pharmacogenetics initiatives were more favorable towards genetic testing applications; they found it to be clinically useful and felt more prepared and confident in their abilities to adopt it into their practice in comparison to those participating in disease genetics initiatives. These results suggest that investigators should explore which attributes of clinical pharmacogenetics (such as the use of simplified genetics-guided recommendations) can be implemented to improve attitudes and preparedness to implement disease genetics in care. Most physicians felt unprepared to use genetic information in their practice; accordingly, major steps should be taken to develop effective clinical tools and training strategies for physicians.

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Returning Actionable Genomic Results in a Research Biobank: Analytic Validity, Clinical Implementation and Resource Utilization

10.1101/2021.08.03.21261489 ◽

2021 ◽

Author(s):

Carrie L. Blout Zawatsky ◽

Nidhi Shah ◽

Kalotina Machini ◽

Emma Perez ◽

Kurt D. Christensen ◽

...

Keyword(s):

Genetic Testing ◽

Laboratory Testing ◽

Clinical Implementation ◽

Research Staff ◽

Staff Support ◽

Pathogenic Variants ◽

The World ◽

Genomic Results ◽

Protocol Cost ◽

Analytic Validity

Over 100 million research participants around the world have had research array-based genotyping (GT) or sequencing (GS), but only a small fraction of these have been offered return of actionable genomic findings (gRoR). Between 2017 and 2021, we analyzed genomic results from 36,417 participants in the Mass General Brigham Biobank and offered to confirm and return pathogenic and likely pathogenic variants (PLPVs) in 59 genes. Variant verification prior to patient recontact revealed that GT falsely identified PLPVs in 44.9% of samples, and GT failed to identify 72.0% of PLPVs detected in a subset of samples that were also sequenced. GT and GS detected verified PLPVs in 1% and 2.5% of the cohort, respectively. Of 256 participants who were alerted that they carried actionable PLPVs, 37.5% actively or passively declined further disclosure. 76.3% of those carrying PLPVs were unaware that they were carrying the variant and over half of those met published professional criteria for genetic testing but had never been tested. This gRoR protocol cost approximately $129,000 USD per year in laboratory testing and research staff support, representing $14 per participant whose DNA was analyzed or $3,224 per participant in whom a PLPV was confirmed and disclosed. These data provide logistical details around gRoR that could help other investigators planning to return genomic results.

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Toward Clinical Implementation of Next-Generation Sequencing-Based Genetic Testing in Rare Diseases: Where Are We?

Trends in Genetics ◽

10.1016/j.tig.2019.08.006 ◽

2019 ◽

Vol 35 (11) ◽

pp. 852-867 ◽

Cited By ~ 11

Author(s):

Zhichao Liu ◽

Liyuan Zhu ◽

Ruth Roberts ◽

Weida Tong

Keyword(s):

Genetic Testing ◽

Next Generation Sequencing ◽

Rare Diseases ◽

Next Generation ◽

Clinical Implementation ◽

Generation Sequencing

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Diagnostic genetic testing for neurodevelopmental psychiatric disorders: closing the gap between recommendation and clinical implementation

Current Opinion in Genetics & Development ◽

10.1016/j.gde.2020.12.016 ◽

2021 ◽

Vol 68 ◽

pp. 1-8

Author(s):

Brenda M Finucane ◽

David H Ledbetter ◽

Jacob AS Vorstman

Keyword(s):

Genetic Testing ◽

Psychiatric Disorders ◽

Clinical Implementation ◽

Closing The Gap ◽

Diagnostic Genetic Testing

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Costing Methods as a Means to Measure the Costs of Pharmacogenomics Testing

The Journal of Applied Laboratory Medicine ◽

10.1093/jalm/jfaa113 ◽

2020 ◽

Vol 5 (5) ◽

pp. 1005-1016 ◽

Cited By ~ 1

Author(s):

Stavroula Siamoglou ◽

Kariofyllis Karamperis ◽

Christina Mitropoulou ◽

George P Patrinos

Keyword(s):

Genetic Testing ◽

Blood Sample ◽

Dna Isolation ◽

Clinical Implementation ◽

Sample Collection ◽

Technical Process ◽

Private Providers ◽

The Cost ◽

First Time ◽

And Personalized Medicine

Abstract Clinical implementation of pharmacogenomics and personalized medicine interventions relies on addressing important financial aspects of the delivery of genetic testing to the patients, be it from public or private providers. Details on how to determine the cost items of the genetic testing are often limited. The goal of this study is to present a costing methodology in order to estimate and measure the costs as far as the technical process of pharmacogenomics testing is concerned. Moreover, an overall cost mindset strategy based on the selective genotyping workflow to guide specialized laboratories of interest effectively is provided. We particularly accounted for the resources consumed within the laboratory premises such as cost of reagents for DNA isolation, cost of consumables, cost of personnel, while costs associated with patient recruitment, blood sample collection and maintenance, administration costs in the hospital, and costs of blood sample shipment were not taken into consideration. Our article presents the first-time detailed information on a costing framework for pharmacogenomic testing that could be employed to laboratories involved in routine clinical implementation of pharmacogenomics.

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Genetic testing in women with early-onset breast cancer: a Traceback pilot study

Breast Cancer Research and Treatment ◽

10.1007/s10549-021-06351-z ◽

2021 ◽

Author(s):

Annelie Augustinsson ◽

Martin P. Nilsson ◽

Carolina Ellberg ◽

Ulf Kristoffersson ◽

Håkan Olsson ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Counseling ◽

Genetic Testing ◽

Pilot Study ◽

Early Onset ◽

Early Onset Breast Cancer ◽

Clinical Implementation ◽

Test Information ◽

Pathogenic Variants ◽

Post Test

Abstract Purpose In Sweden, a Traceback approach, i.e., a retrospective genetic outreach activity, among cancer patients is not normally used in clinical practice. In this pilot study, we wanted to evaluate a Traceback strategy for possible future clinical implementation and investigate why not all women with early-onset breast cancer underwent genetic testing when they were first diagnosed. Methods Out of all women (n = 409) diagnosed with breast cancer at ≤ 35 years in Southern Sweden between 2000 and 2017, 63 had not previously been tested. These women were offered an analysis of the genes BRCA1, BRCA2, PALB2, CHEK2, and ATM through a standardized letter. Subsequently, women with normal test results were informed through a letter and carriers of pathogenic variants were contacted through a telephone call and offered in-person genetic counseling. All tested women were asked to complete a follow-up questionnaire regarding previously not having attended genetic counseling and testing and their experiences of the current retrospective approach. Results Out of the invited women, 29 (46%) underwent genetic testing and 27 (43%) answered the questionnaire. Pathogenic variants were identified in BRCA1 (n = 2), CHEK2 (n = 1), and ATM (n = 1). The main reason for previously not having undergone genetic testing was not having received any information from their physicians. Most study participants were satisfied with both written pre- and post-test information. Conclusion The process with retrospective identification, written pre-test information, and genetic testing, followed by in-person counseling for carriers of pathogenic variants only, was well accepted. This has implications for future Traceback implementation programs.

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A Systematic Review on the Impact of Genetic Testing for Familial Melanoma II: Psychosocial Outcomes and Attitudes

Dermatology ◽

10.1159/000513576 ◽

2021 ◽

pp. 1-11

Author(s):

Clare A. Primiero ◽

Tatiane Yanes ◽

Anna Finnane ◽

H. Peter Soyer ◽

Aideen M. McInerney-Leo

Keyword(s):

Genetic Testing ◽

Perceived Risk ◽

Psychosocial Outcomes ◽

Genetic Mutation ◽

Cochrane Library ◽

Cognitive Responses ◽

Clinical Implementation ◽

Familial Melanoma ◽

Genetic Test Results ◽

The Impact

Background: Although genetic testing for known familial melanoma genes is commercially available, clinical implementation has been restrained as utility is unclear, concerns of causing psychological distress are often cited, and consumer interest and perceptions are not well understood. A review of studies exploring participant-reported psychosocial outcomes and attitudes towards genetic testing for familial melanoma will provide insight into common emotional and cognitive responses. Methods: Database searches of PubMed, Embase, CINAHL, PsycINFO and the Cochrane Library were conducted using a date range of January 1995 to June 2020. Studies examining any psychosocial outcomes alongside genetic testing (real or hypothetical), in participants described as having a high risk of melanoma, were eligible. A narrative synthesis of results was used to describe psychosocial outcomes and summarise participant beliefs and attitudes towards genetic testing. Results: Limited evidence of adverse psychosocial outcomes was found. No impacts on perceived risk or control were reported, and minimal decisional regret was recorded. Generalised distress was comparable between both genetic mutation carriers and non-carriers, often decreasing over time from pretesting levels. Melanoma-specific distress was frequently higher in carriers than non-carriers; however, this difference was present prior to testing and often associated with personal melanoma history. Overall, participants’ attitudes towards testing were largely positive, with benefits more frequently described than limitations, and support for testing minors was strong. Conclusions: This review has found evidence of few adverse psychological outcomes following genetic testing. There was no indication of increased distress after genetic test results had been disclosed. If these findings were replicated in additional, larger, diverse populations over a longer follow-up period, this would be compelling evidence to guide clinical recommendations.

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