Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility

Bradbury, Angela R.; Patrick‐Miller, Linda; Long, Jessica M.; Powers, Jacquelyn; Stopfer, Jill E.; Forman, Andrea; Rybak, Christina; Mattie, Kristin; Brandt, Amanda; Chambers, Rachelle; Chung, Wendy K.; Churpek, Jane E.; Daly, Mary B.; DiGiovanni, Laura; Farengo-Clark, Dana; Fetzer, Dominique; Ganschow, Pamela; Grana, Generosa; Gulden, Cassandra; Hall, Michael J.; Kohler, Lynne; Maxwell, Kara N.; Merrill, Shana L.; Montgomery, Susan; Mueller, Rebecca; Nielsen, Sarah M.; Olopade, Olufunmilayo I.; Rainey, Kimberly; Seelaus, Christina; Domchek, Susan M.

doi:10.1038/gim.2014.134

Cited by 79 publications

(94 citation statements)

References 40 publications

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“…7,18 In this model, tier 1 "indispensable" information is presented to all patients. More specific tier 2 information is provided to support variable informational needs among diverse patient populations.…”

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

“…Further, knowledge-in particular knowledge of the limitations of multiplex testing-increased following the tiered-binned pretest counseling model. Understanding the limitations of genetic testing is a key component of informed consent 14,18 and is particularly important in the setting of genetic tests with variable utility and uncertain risks. 3,7,37 Thus, these patient-reported data suggest that this new tiered-binned approach to genetic counseling has the potential to increase knowledge and to support informed decision making in the context of next-generation sequencing, although further larger studies designed to evaluate outcomes and the clinical application of this model are warranted.…”

Section: Original Research Articlementioning

confidence: 99%

“…This model highlights various testing options for individual patients, including limited or targeted testing (e.g., BRCA1/2 only) or deferring testing for moderate-penetrance genes. 18 For example, after pretest counseling participants could elect to decline the myRisk panel and consider other targeted genetic testing (e.g., BRCA1/2 only, TP53, PTEN, or Lynch syndrome genes, depending on personal and family history). Thirty-six standardized pretest and 15-22 (depending on test result and context) standardized posttest topics were developed to minimize differences among genetic counseling sessions.…”

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

“…More specific tier 2 information is provided to support variable informational needs among diverse patient populations. 18 "Binning" clinically relevant information into groups is used to minimize information overload, support informed decision making, and facilitate adaptive responses to testing. Seven essential elements of informed consent are provided to address the unique limitations, risks, and uncertainties of multiplex testing.…”

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

“…Thirty-six standardized pretest and 15-22 (depending on test result and context) standardized posttest topics were developed to minimize differences among genetic counseling sessions. 18 Genetic counselors underwent protocol training, including mock counseling sessions with individualized feedback. Genetic counselors completed counseling checklists, and sessions were audiotaped.…”

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

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Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing

Bradbury

Patrick‐Miller

Egleston

et al. 2016

Genetics in Medicine

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119

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Original research article INTRODUCTION Multiplex (i.e., multigene) panels including both high-and moderate-penetrance cancer susceptibility genes are currently being used in clinical practice despite questions regarding their clinical utility and no standard approach to genetic counseling and delivery. [1][2][3][4][5][6] The inclusion of genes with varying penetrance and clinical utility has raised concerns. 7 There are both advantages and disadvantages of multigene testing (as opposed to traditional phenotype-driven sequential testing), presenting challenges to patient education and informed decision making.3,7-10 The advantages and disadvantages of testing options must be shared with patients so they can make an informed decision regarding genetic testing. 8,[11][12][13][14] Traditional comprehensive models for pretest counseling and informed consent could be associated with information overload and poor informed decision making. 7,15 In addition, multiplex testing has the potential to increase anxiety, uncertainty, and the adoption of inappropriate screening procedures or risk-reducing surgeries. 3,7 Effective genetic education and counseling could minimize these risks and enhance adaptive responses to receiving multiplex results. 13This study has several aims. First, we sought to obtain patient feedback regarding the tiered-binned model for informed consent and counseling for multiplex testing among patients with a personal or family history of breast cancer. Second, we sought to begin to evaluate patient uptake of testing after pretest counseling and to evaluate informed decision making with the tiered-binned model. Third, we sought to begin to explore short-term cognitive and affective outcomes in clinical populations to better understand the potential risks, benefits, and utilities of incorporating multiplex genetic testing for breast cancer susceptibility assessment in clinical care. Purpose: The risks, benefits, and utilities of multiplex panels for breast cancer susceptibility are unknown, and new counseling and informed consent models are needed. We sought to obtain patient feedback and early outcome data with a novel tiered-binned model for multiplex testing.Methods: BRCA1/2-negative and untested patients completed preand posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing. Results:Of 73 patients, 49 (67%) completed pretest counseling. BRCA1/2-negative patients were more likely to proceed with multiplex testing (86%) than those untested for BRCA1/2 (43%; P < 0.01). Many patients declining testing reported concern for uncertainty and distress. Most patients would not change anything about their pre-(76%) or posttest (89%) counseling sessions. Thirtythree patients (72%) were classified as making an informed choice, including 81% of those who proceeded with multiplex testing. Knowledge increased significantly. Anxiety, depression, uncertainty, and cancer worry did not significantly increase with multiplex testing. Conclusion:Some pati...

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Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

Section: Original Research Articlementioning

confidence: 99%

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

Section: Tiered-binned Genetic Counseling Protocol and Multiplex Testingmentioning

confidence: 99%

See 3 more Smart Citations

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing

Bradbury

Patrick‐Miller

Egleston

et al. 2016

Genetics in Medicine

Self Cite

119

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Multigene Panel Testing in Oncology Practice

Kurian

Ford

2015

JAMA Oncol

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A great success of modern human genetics is the identification of specific genes that, when altered, confer clinically recognized traits, such as cancer susceptibility, and enable predictive genetic testing. In past decades, cost and turnaround time limited cancer genetic risk assessment, and it was rarely feasible to test a patient for more than 1 well-defined condition (eg, hereditary breast ovarian cancer [HBOC] or Lynch syndrome). Transformative sequencing advances now permit massively parallel, rapid analysis of many genes, making the "$1000 genome" an imminent reality. In June 2013, long-term barriers to cancer genetic testing were breached by a remarkable convergence of events: the disclosure of her BRCA1 mutation by the actress Angelina Jolie, which dramatically increased public awareness and demand for genetic testing 1 ; and the US Supreme Court decision against gene patenting, which allowed competition to reduce the price of BRCA1 and BRCA2 (BRCA1/2) testing. 2 Incentives quickly shifted toward sequencing more genes as laboratories competed to offer panels of increasing numbers of genes (from 6 to >100) at decreasing prices. Perhaps because testing costs have fallen so greatly, insurers rarely object to multigene panels as a means of diagnosing recognized syndromes (eg, HBOC) when relevant guidelines are met. However, most payers will not cover more than 1 cancer risk assessment test, creating an incentive to sequence any genes of interest concurrently rather than sequentially. In short, multigene panels have entered the clinic, 3 and there seems little chance of forcing the genie back into the bottle. Fortunately, multigene panels offer significant benefits over sequential single-gene testing. They are cheaper, faster, and more efficient for differential diagnosis. Most important, they may identify deleterious mutations that the pedigree would not suggest, particularly for families with cancer patterns that deviate from recognized syndromes. These advances come with drawbacks, however, related to the lack of a testing track record for many genes on commercially available panels. 4 Panel testing is complicated by 3 levels of uncertainty about mutations in less widely tested genes, regarding (1) the magnitude of cancer risk (penetrance), (2) the anatomical and age-specific scope of cancer risk, and (3) the clinical relevance of missense variants in genes for which the spectrum of normalcy is poorly defined. Variants of uncertain significance (VUS) increase in frequency with the number of genes sequenced, 5 and, if skilled genetic counseling is not provided, this may cause anxiety and unwarranted interventions. Recently, concerns have arisen that technical advances in genomics have outpaced our ability to provide safe, ethical care. When guided by appropriate ex

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Ethical Issues in Multiplex Genetic Testing

Kilbride

Bradbury

2020

Encyclopedia of Life Sciences

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As a result of technological advancements, multiplex (or multigene) genetic tests are increasingly available both inside and outside the clinical setting. Multiplex genetic tests include: expanded carrier screening (ECS), preimplantation genetic testing (PGT), prenatal genetic diagnosis (PND), newborn screening (NBS), predictive genetic testing, diagnostic genetic testing, whole‐genome sequencing (WGS) and whole‐exome sequencing (WES). Many of these tests include dozens – even hundreds – of genes that are associated with a wide range of genetic conditions. While multiplex genetic tests have significant advantages over more targeted approaches, they also raise ethical concerns, related to informed consent, the implications of genetic selection and uncertainty. Outside the clinical setting, direct‐to‐consumer (DTC) genetic testing also raises a set of ethical concerns, including some that are specific to the DTC model. Key Concepts Multiplex genetic testing has important advantages over targeted approaches, including efficiency, cost‐effectiveness and the detection of unanticipated genetic risks. There are different types of multiplex genetic tests. Multiplex genetic testing raises ethical concerns about informed consent, the implications of genetic selection and uncertainty. Obtaining informed consent to multiplex genetic testing is challenging because multiplex tests often analyse genes that are associated with a range of diseases, penetrance estimates and medical management strategies. Genetic testing, particularly of embryos and fetuses, raises ethical concerns about genetic selection for or against certain traits. Multiplex genetic tests can lead to significant uncertainty for patients interested in learning about their own genetic risks or those of their current or future children. Multiplex genetic testing is increasingly available through direct‐to‐consumer (DTC) platforms, raising unique ethical questions about the nature of informed consent outside the clinical setting. In order to realise the promise of multiplex genetic tests, there is a need to continue studying the risks and benefits of different types of tests by collecting and evaluating outcome data.

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Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility

Cited by 79 publications

References 40 publications

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing

Multigene Panel Testing in Oncology Practice

Ethical Issues in Multiplex Genetic Testing

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