Genetic Testing Practices Research Articles

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path_MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path_MSH2 were identified in 37% of females and males, followed by path_PMS2 in 11% of females and 8% of males, path_MSH6 in 13% of females and 3% of males (p < 0.001) and path_EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries.

Global celebrities' effect on health awareness among Jordanians: A study using the case of Angelina Jolie

Celebrities' health decisions have long been associated with heightened awareness and health trend changes. This is the first study conducted in an Arab population investigating the impact of international celebrity news on local communities using the case of Angelia Jolie's (AJ) prophylactic mastectomy and oophorectomy surgeries. The objective was to measure the effect of publicized medical information on cancer genetic testing knowledge, attitudes, and practices (KAP). This is a cross-sectional study using a semi-structured, self-administered questionnaire for clinic visitors at the King Hussein Cancer Center (KHCC). We had predominantly female (n=262, 66.3%) and healthy participants (n=248, 66.5%). Approximately 80.7% (n=330) recognized AJ, the actress, and of these, 71% (n=232) were aware of her recent diagnosis and prophylactic surgeries. Males reported a higher knowledge score (p<.001). However, females had more initiative to seek information (18.3% vs. 10.1%; p=.04). People aware of Angelina's prophylactic procedures were inclined to seek information regarding cancer genetics (20.8% vs. 9.6% p=.003). Breast and ovarian cancer patients were more likely than other cancer patients to encourage family members to undergo prophylactic surgery in case of BRCA1/2 mutations (39.2% vs. 17.1% p=.03). Ninety-three percent of the sample lacked knowledge regarding the availability of cancer genetic testing in Jordan. Results highlight a clear effect of celebrity medical news on our population, as well as openness to consider genetic testing as an early detection tool for women with a family history of breast and/or ovarian cancer. Generalization of these results to the population of Jordan requires further studies.

Equipoise of recent estimated Down syndrome live births in Japan.

To support people with Down syndrome (DS), it is essential to know and predict the number of live births of children with this condition. In this study, we estimated DS live birth rates on the basis of maternal age distribution and numbers of births in the general population, the maternal-age specific chance for a live birth of a child with DS, and the prenatal diagnosis/termination rate. The total number of live births in Japan decreased to less than 1 million in 2016 and the percentage of women aged 35 years old or over giving birth has increased by sixfold. Prenatal genetic testing in Japan has gradually become more widespread, and 20% of all cases of DS were diagnosed prenatally in 2016. Meanwhile, the annual projected number of DS live births has remained steady at around 2,200 (22 per 10,000 births). In 2016, it was estimated that 70% of all DS babies were born to women of advanced maternal age (AMA). Given that Japan is facing a decreasing birth rate and an aging population, adoption of the practice of prenatal genetic testing for AMA has balanced the number of DS births over the last 7 years from 2010.

Genetic testing for congenital non-syndromic sensorineural hearing loss

IntroductionApproximately 60% of congenital pediatric hearing loss is of genetic etiology. To evaluate non-syndromic sensorineural hearing loss (NSSNHL), guidelines emphasize the use of comprehensive genetic testing (CGT) with next generation sequencing (NGS), yet these tests have limited accessibility, and potential CGT results may not be well understood. Thus, our objective was to analyze genetic testing practices and results for pediatric patients with NSSNHL. MethodsThis was a retrospective chart review of pediatric patients (<18 years) diagnosed with NSSNHL from 2014 to 2017 at a tertiary pediatric hospital. Demographics, clinical data, CGT results, genetic testing practices and referral patterns were recorded and descriptively analyzed. Logistic regression models identified patient characteristics associated with pathogenic variants (PV) and variants of unknown significance (VOUS). Results430 patients with congenital NSSNHL were included in the study. Genetic testing was ordered for 28% (n = 122) and resulted for 16% (n = 68). Most of the ordered tests (89%, n = 109) were the CGT panel. A majority (62%, n = 97) of the time in which genetic testing was not ordered, a referral for genetics consultation was placed. Amongst those with CGT results, a definitive genetic etiology was identified in 25% (n = 13), with less than half due to variants of GJB2/6. At least one PV was identified for 33% (n = 18), while at least one VOUS for 93% (n = 51). There were no significant differences in PV presence or number of VOUS across any characteristic except race. When compared to Caucasians, African Americans had significantly higher rates of VOUS with a rate ratio and 95% CI of 1.61 [1.11–2.34], p = 0.01, and Asians trended towards higher rates (1.96 [0.95–4.05], p = 0.06). ConclusionsCGT is of high utility in the identification of relevant genetic variants and definitive genetic etiologies for pediatric patients with NSSNHL. Though guidelines recommend the early use of CGT, there are many barriers to appropriate testing and counseling, leading to low rates of CGT use at this single institution.

Exploring the Regulation of Genetic Testing in Sport

This article investigates the legal implications of the use of genetic testing in sport, that is, the analysis of human DNA to detect particular genetic traits and variations, or susceptibility to conditions. As science makes significant strides in the understanding of our genetic information, the search for the genetic components which separate winners and losers in sport follows. Although the practice of genetic testing in sport is not currently commonplace, there are some examples of genetic information being used by sports clubs and governing bodies to make decisions about an athlete’s capability to perform. This article examines how this practice could disproportionately interfere with an individual’s human rights and result in genetic discrimination if information is used for selection and employment purposes. It reviews some of the hard and soft law measures that regulate genetic testing at an international, regional and domestic level. The position of sport within this regulatory framework is uncertain, given the unique way in which sports regulation functions and interacts with the law. Nevertheless, the article concludes that the tendency of the law to treat discrimination in sport differently to other areas of society could leave athletes vulnerable. Whilst genetic information may be useful for understanding genetic traits and their relationship with athletic performance, going beyond this to select athletes on the basis of genetics is discouraged and the interests of sport should be fairly balanced against the human rights of the athlete.

Lack of consensus in ALS genetic testing practices and divergent views between ALS clinicians and patients

Recent advances in ALS gene discovery have both empowered and challenged clinicians providing evaluation and care for persons with ALS, many of whom seek an answer as to the cause of their condition. In order to study clinician practices and attitudes towards genetic testing, we surveyed members of the Northeast ALS Consortium, an international group of specialist ALS clinicians; responses were received from 80 of 255 (response rate = 31.4%). While 92.3% indicated they offered genetic testing to patients with familial ALS, 57.0% offered testing to patients with ALS and a family history of dementia, and 36.9% offered testing to patients with sporadic ALS, revealing a lack of consensus with respect to the approach to the typical ALS patient encountered in clinical practice. In addition, comparison of clinician and patient attitudes towards genetic testing revealed that clinicians valued the scientific potential of testing, but were less likely to say they would have testing themselves, or to see the value in testing for family members. People with ALS were more likely to see value of testing for themselves and for family members, and less likely to strongly value the scientific potential of testing.

Mismatch repair/microsatellite instability (MMR/MSI) testing practices among United States physicians treating patients (pts) with advanced/metastatic colorectal cancer (mCRC).

533 Background: Approximately 12-15% of all CRCs are associated with defects in the DNA MMR pathway. NCCN 2017 guidelines endorsed universal MMR/MSI testing for all pts with a personal history of CRC. The study objective was to assess US physicians’ MMR/MSI genetic testing practices for mCRC pts. Methods: A non-interventional, cross-sectional online survey was conducted among 151 physicians (91 oncologists, 15 surgeons and 45 pathologists) treating mCRC pts in the US. A draft survey was first developed based on a targeted literature review and exploratory interviews with 15 physicians, and then pilot tested with a new series of 10 physicians. Physicians were eligible if they were US based with at least 5 years of experience treating CRC pts, had at least one mCRC pt in their routine care in the past 6 months of practice, and experienced with MMR/MSI testing including having ordered at least 1 MMR/MSI test for CRC in the past 6 months. Physicians were invited to participate through a market research panel. Descriptive and logistic regression analyses were performed. Results: Awareness of specific MMR/MSI testing guidelines was high (N = 127, 84.1%). Of those, 93.7% (119/127) physicians had awareness of specific published guidelines with majority 67.2% (80/119) being aware of NCCN guidelines. Universal testing for all CRC pts was performed by 68.9% (104/151) physicians, while 29.8% (45/151) selectively orders the test for some CRC pts. Key barriers for testing included insufficient tissue sample to enable running the test (48.3%, 73/151), patient refusal to have the test done (35.8%, 54/151) and insurance cost concerns for the pts (31.1%, 47/151), while 27.2% (41/151) reported no barriers. There were no statistically significant differences based on physician specialty, practice type and years of practice. Conclusions: The survey demonstrated high awareness and compliance with MMR/MSI testing guidelines although universal testing rates seem to be suboptimal. Addressing the key physician barriers to testing along with increased communication and education on the benefits of testing may help to enhance testing rates.

Genetic Testing Practices of Genetic Counselors, Geneticists, and Pediatric Neurologists With Regard to Childhood-Onset Neurogenetic Conditions.

Identifying genetic diagnoses for neurologic conditions with a considerable hereditary component, such as autism spectrum disorder, intellectual disability, and epilepsy, is critical to providing proper medical management for patients and their families. However, many patients with these conditions are not tested appropriately or receive no genetic testing at all. The current study was designed to characterize the genetic testing practices of the providers most likely to evaluate or order genetic testing for these patients: pediatric neurologists, geneticists, and genetic counselors. Significant variance was present between testing strategies selected by pediatric neurologists and those by geneticists and genetic counselors, supporting the need for updated genetic testing guidelines that are consistent across specialties. Pediatric neurologists also report lower confidence in ordering genetic testing and desire further education regarding genetic testing. Together, these results propose that continued integration of genetics providers, such as genetic counselors, into pediatric neurology clinics may improve utilization of genetic testing while reducing the burden on pediatric neurologists.

Genetic Testing and Clinical Management Practices for Variants in Non-BRCA1/2 Breast (and Breast/Ovarian) Cancer Susceptibility Genes: An International Survey by the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Clinical Working Group.

To describe a snapshot of international genetic testing practices, specifically regarding the use of multigene panels, for hereditary breast/ovarian cancers. We conducted a survey through the Evidence-Based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) consortium, covering questions about 16 non-BRCA1/2 genes. Data were collected via in-person and paper/electronic surveys. ENIGMA members from around the world were invited to participate. Additional information was collected via country networks in the United Kingdom and in Italy. Responses from 61 cancer genetics practices across 20 countries showed that 16 genes were tested by > 50% of the centers, but only six (PALB2, TP53, PTEN, CHEK2, ATM, and BRIP1) were tested regularly. US centers tested the genes most often, whereas United Kingdom and Italian centers with no direct ENIGMA affiliation at the time of the survey were the least likely to regularly test them. Most centers tested the 16 genes through multigene panels; some centers tested TP53, PTEN, and other cancer syndrome-associated genes individually. Most centers reported (likely) pathogenic variants to patients and would test family members for such variants. Gene-specific guidelines for breast and ovarian cancer risk management were limited and differed among countries, especially with regard to starting age and type of imaging and risk-reducing surgery recommendations. Currently, a small number of genes beyond BRCA1/2 are routinely analyzed worldwide, and management guidelines are limited and largely based on expert opinion. To attain clinical implementation of multigene panel testing through evidence-based management practices, it is paramount that clinicians (and patients) participate in international initiatives that share panel testing data, interpret sequence variants, and collect prospective data to underpin risk estimates and evaluate the outcome of risk intervention strategies.

The influence of Malay cultural beliefs on breast cancer screening and genetic testing: A focus group study.

Malays comprise an Asian cultural group reported to have low breast cancer screening uptake rates and poor cancer outcomes. Little is known about Malay cultural factors influencing beliefs and practice of cancer screening and genetic testing. Our study aims to explore health beliefs of Malay women around breast cancer screening and genetic testing. We conducted focus groups among healthy English-speaking Malay women in Singapore, aged 40 to 69years, using a structured guide developed through literature review, expertise input and participant refinement. Thematic analysis was conducted to extract dominant themes representing key motivators and barriers to screening and genetic testing. We used grounded theory to interpret results and derive a framework of understanding, with implications for improving uptake of services. Five focus groups (four to six participants per group) comprising 27 women were conducted to theme saturation. Major themes were (a) spiritual and religious beliefs act as barriers towards uptake of screening and genetic testing; (b) preference for traditional medicine competes with Western medicine recommendations; (c) family and community influence health-related decisions, complexed by differences in intergenerational beliefs creating contrasting attitudes towards screening and prevention. Decisions to participate in breast cancer screening and genetic testing are influenced by cultural, traditional, spiritual/religious, and intergenerational beliefs. Strategies to increase uptake should include acknowledgement and integration of these beliefs into counseling and education and collaboration with key influential Malay stakeholders and leaders.

Evolving Intersection Between Inherited Cancer Genetics and Therapeutic Clinical Trials in Prostate Cancer: A White Paper From the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium.

Advances in germline genetics, and related therapeutic opportunities, present new opportunities and challenges in prostate cancer. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group was established to address genetic testing for men with prostate cancer, especially those with advanced disease undergoing testing for treatment-related objectives and clinical trials. The Prostate Cancer Clinical Trials Consortium Germline Genetics Working Group met monthly to discuss the current state of genetic testing of men with prostate cancer for therapeutic or clinical trial purposes. We assessed current institutional practices, developed a framework to address unique challenges in this population, and identified areas of future research. Genetic testing practices in men with prostate cancer vary across institutions; however, there were several areas of agreement. The group recognized the clinical benefits of expanding germline genetic testing, beyond cancer risk assessment, for the goal of treatment selection or clinical trial eligibility determination. Genetic testing for treatment selection should ensure patients receive appropriate pretest education and consent and occur under auspices of a research study whenever feasible. Providers offering genetic testing should be able to interpret results and recommend post-test genetic counseling for patients. When performing tumor (somatic) genomic profiling, providers should discuss the potential for uncovering germline mutations and recommend appropriate genetic counseling. In addition, family members may benefit from cascade testing and early cancer screening and prevention strategies. As germline genetic testing is incorporated into practice, further development is needed in establishing prompt testing for time-sensitive treatment decisions, integrating cascade testing for family, ensuring equitable access to testing, and elucidating the role of less-characterized germline DNA damage repair genes, individual gene-level biologic consequences, and treatment response prediction in advanced disease.

A theory-informed systematic review of clinicians' genetic testing practices.

This systematic literature review investigates factors impacting on clinicians' decisions to offer genetic tests in their practice, and maps them to a theoretical behaviour change framework. Better understanding of these factors will inform the design of effective interventions to integrate genomics tests into clinical care. We conducted a narrative synthesis of empirical research of medical specialists' perspectives on and experiences of offering genetic tests to their patients. This review was based upon the PRISMA statement and guidelines for reviewing qualitative research. Four electronic data sources were searched-MEDLINE, EMBASE, CINAHL, PubMed. Studies were independently assessed by two authors. Content analysis was applied to map the findings of included studies to a framework validated for behaviour and implementation research, the Theoretical Domains Framework (TDF). The TDF describes 14 factors known to influence behaviour and has been applied in diverse clinical settings to understand and/or modify health professional behaviour. Thirty-four studies published in 39 articles met inclusion and quality criteria. Most studies were published after 2011 (54%), Northern American (82%), quantitative in design (68%) and addressed familial cancer genetic tests (53%). Of the 14 TDF factors, 13 were identified. The three most common factors were: Environmental Context and Resources (n = 33), Beliefs about Consequences (n = 26), and Knowledge (n = 23). To support the adoption of genomic tests beyond specialist services, nuanced interventions targeting considerations beyond clinician education are needed. For instance, interventions addressing organisational constraints which may restrict clinicians' ability to offer genomic tests are required alongside those targeting factors intrinsic to the clinician.

Genetic testing and clinical management practices for variants in non-BRCA1/2 breast (and/or ovarian) cancer susceptibility genes: An international survey by the Enigma Clinical Working Group.

1539Background: Advances in massively parallel sequencing technologies have made multigene panels affordable and have revolutionized genetic testing for hereditary breast and ovarian cancer. Throug...

Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices

Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1/BRCA2. We employed an online survey of 65 questions covering four areas: laboratory characteristics, details on technological methods, variant classification, and client-support information. Eight United States (US) laboratories and 78 non-US laboratories completed the survey. Most laboratories (93%; 80/86) used MPS platforms to identify variants. Laboratories differed widely on: (1) technologies used for large rearrangement detection; (2) criteria for minimum read depths; (3) non-coding regions sequenced; (4) variant classification criteria and approaches; (5) testing volume ranging from 2 to 2.5 × 105 tests annually; and (6) deposition of variants into public databases. These data may be useful for national and international agencies to set recommendations for quality standards for BRCA1/BRCA2 clinical testing. These standards could also be applied to testing of other disease genes.

Status of BRCA1/2 Genetic Testing Practices in Korea (2014)

배경: 2014년 국내에서 시행했던 BRACA1/2 유전자 검사의 현황을 파악하기 위해서 진행하였다. 방법: 각 기관의 유전자 검사 담당 전문가에게 2015년 7월 28일부터 8월 10일까지 전자메일을 통해 온라인 설문조사를 시행하여, 15개의 기관 중 답변을 한 11개의 기관의 답변을 분석하였다. 결과: 2014년도에 시행된 BRACA1/2 유전자 검사건수는 11개 기관 전체 평균 192건으로, 6개의 기관은 100건 미만, 5개의 기관은 100건 이상이었다. 유전자 검사를 위해 가장 많이 사용하는 방법은 Sanger sequencing으로 전체 기관에서 사용하고 있었고, 2개의 기관에서 Multiplex Ligation-dependent Probe Ampli cation (MLPA)을 함께 사용하고 있었다. 유전자 검사 결과 분석 시 사용하는 소프트웨어는 Sequencher (81.81%), Seqscape (27.27%), Codoncode Aligner (9.09%) 순이었고 각 기관마다 유전자 검사 해석 시 따르고 있는 가이드라인이 달랐다. 결론: 2014년도에 BRACA1/2 유전자 검사를 시행한 11개 기관만을 관찰하였지만, 본 연구로 국내의 표준화된 가이드라인이 필요함을 보여주었다.

Knowledge, Attitudes, and Practices of Women Toward Prenatal Genetic Testing.

Objectives:We aim to address public knowledge, attitudes, and practices relative to prenatal genetic testing as a starting point for policy development in Jordan.Study design:We conducted a cross-sectional prenatal genetic testing knowledge, attitudes, and practices survey with 1111 women recruited at obstetrics and gynecology clinics nationwide. Data were analyzed using a variety of descriptive and inferential statistical tests.Results:The overwhelming majority (>94%) of participants considered prenatal genetic testing, particularly non-invasive prenatal genetic screening, procedures to be good, comfortable, and reasonable, even when the non-diagnostic nature of non-invasive prenatal genetic screening was explained. Likewise, 95% encouraged the implementation of non-invasive prenatal genetic screening within the Jordanian health system, but most preferred it to remain optional. However, women in higher-risk age brackets, in consanguineous marriages, and with less education were significantly less interested in learning about non-invasive prenatal genetic screening. Only 60% of women interviewed were satisfied with the services provided by their obstetric/gynecologist. The more satisfied the women were, the more they are likely to adapt non-invasive prenatal genetic screening.Conclusions:In sum, although the data support the receptivity of Jordanian women to national implementation of non-invasive prenatal genetic screening, such policies should be accompanied by health education to increase the genetic literacy of the population and to engage high-risk populations. Thus, this offers rare insight into the readiness of 1 particular Arab population to adapt non-invasive prenatal genetic screening technologies.

Chapter 3 - Ethical issues in neurogenetics

Many neurogenetic conditions are inherited and therefore diagnosis of a patient will have implications for the patient's relatives and can raise ethical issues. Predictive genetic testing offers asymptomatic relatives the opportunity to determine their risk status for a neurogenetic condition, and professional guidelines emphasize patients' autonomy and informed, voluntary decision making. Beneficence and nonmaleficence both need to be considered when making decisions about disclosure and nondisclosure of genetic information and test results. There can be disclosure concerns and challenges in determining whose autonomy to prioritize when a patient makes a genetic testing decision that can reveal the genetic status of a relative (e.g., testing an adult child when the at-risk parent has not been tested). Ethical issues are prominent when genetic testing for neurogenetic conditions is requested prenatally, on minors, adoptees, adult children at 25% risk, and for individuals with psychiatric issues or cognitive impairment. Neurogenetic conditions can result in cognitive decline which can affect decisional capacity and lead to ethical challenges with decision making, informed consent, and determining the patient's ability to comprehend test results. The ethical implications of genetic testing and emerging issues, including direct-to-consumer genetic testing, disclosure of secondary findings from genomic sequencing, and use of apolipoprotein E testing in clinical and research settings, are also discussed. Resources for information about genetic testing practice guidelines, insurance laws, and directories of genetics clinics are included.

Genetic Testing: Challenges and Changes in Testing for Hereditary Cancer Syndromes

The practice of genetic testing for hereditary cancer syndromes has changed dramatically in recent years, and patients often approach oncology nurses requesting information about genetic testing. . This article aims to explore changes in cancer genetics, the role of genetics professionals in providing comprehensive genetic care, and the implications of these new developments in genetics for oncology nurses. . A literature review was conducted and focused on articles about the updating of genetic tests with panel testing, insurance changes, alternative genetic counseling strategies, and direct-to-consumer genetic testing. . Oncology nurses play an important role in identifying and referring patients, including those who have tested negative for hereditary susceptibility genes, to genetics professionals. Genetics professionals can assist with insurance issues, interpretation of test results, clarification when a variant of unknown clinical significance is detected, and recommendations for care based on personal and family history and testing results. Oncology nurses can assist families with understanding the limitations of direct-to-consumer genetic testing.

Letter re: The autism "epidemic": Ethical, legal, and social issues in a developmental spectrum disorder.

Graf et al.1 wrote an interesting review on autism spectrum disorder (ASD), emphasizing the term “autism epidemic,” supported by an editorial.2 Among other factors, increasing ASD diagnoses can be attributed to broader diagnostic criteria and the recognition of ASD existence differentiated from other neurodevelopmental diseases.2–4 One important issue, defended by the authors, is early screening and diagnosis with emphasis on the evolving practice of genetic testing for ASD.1

FDA Approval of PARP Inhibitors and the Impact on Genetic Counseling and Genetic Testing Practices.

In December 2014, the FDA approved olaparib, a poly(ADP-ribose) polymerase inhibitor (PARPi) for ovarian cancer patients who have failed three or more lines of chemotherapy and have a germline BRCA1/2 mutation identified through a companion diagnostic test (BRACAnalysis CDx™ (CDx™)) offered exclusively by Myriad Genetic Laboratories. This study explored the impact of PARPi/CDx™ on genetic counselors' (GCs) counseling and testing practices. One hundred twenty three GCs responded to an online survey regarding pre- and post-FDA approval referral patterns, testing strategies/influences, and anecdotal experiences with insurance coverage of PARPi for BRCA1/2 positive patients through a non-CDx™ platform. Following PARPi approval, 40% of respondents reported an increase in overall referrals of ovarian cancer patients and 20% had an increase in post-test counseling only referrals. The majority (61.9%) of respondents reported no change in genetic testing strategy, and there was no change in factors influencing choice of testing laboratory. Nearly all (98.1%) respondents who had experience with insurance covering PARPi indicated approval with mutations identified via non-CDx™ testing. Respondents indicated an increase in referral volume following FDA approval of PARPi/CDx™, but did not report changes in testing practices. Respondents were not aware of PARPi insurance coverage denial in the absence of CDx™.