Impact of direct-to-consumer advertising for hereditary breast cancer testing on genetic services at a managed care organization: a naturally-occurring experiment.

PURPOSE: To describe the impact of Myriad Genetics, Inc.'s direct-to-consumer advertising (DTC-ad) campaign on cancer genetic services within two Managed Care Organizations, Kaiser Permanente Colorado (KPCO), Denver, Colorado, where the ad campaign occurred, and Henry Ford Health System (HFHS), Detroit, Michigan, where there were no advertisements. METHODS: The main outcome measures were the changes in number and pretest mutation probability of referrals approved for cancer genetic services at KPCO and HFHS during the campaign versus the year prior, and mutation probability of those undergoing testing. RESULTS: At KPCO, referrals increased 244% during the DTC-ad compared to the same time period a year earlier (P value<0.001). The proportion of referrals at high pretest probability of a mutation (10% or greater) dropped from 69% the previous year to 48% during the campaign (P value<0.001). There was no significant change in pretest mutation probability among women who underwent testing between the two time periods. HFHS reported no significant change between the two time periods for numbers or mutation probability of referrals, or for mutation probability of women tested. CONCLUSION: The DTC-ad caused significant increase in demand for cancer genetic services. In the face of potential future DTC-ad for inherited cancer risk, providers and payers need to consider the delivery of genetic services and genetic education for persons of all risk levels.     

Investigating genetic discrimination in Australia: a large-scale survey of clinical genetics clients

We report first results from the Australian Genetic Discrimination Project of clinical genetics services clients' perceptions and experiences regarding alleged differential treatment associated with having genetic information. Adults (n = 2667) who had presented from 1998 to 2003 regarding predictive or presymptomatic testing for designated mature-onset conditions were surveyed; 951/1185 respondents met inclusion criteria for current asymptomatic status. Neurological conditions and familial cancers were primary relevant conditions for 87% of asymptomatic respondents. Specific incidents of alleged negative treatment, reported by 10% (n = 93) of respondents, occurred in life insurance (42%), employment (5%), family (22%), social (11%) and health (20%) domains. Respondents where neuro-degenerative conditions were relevant were more likely overall to report incidents and significantly more likely to report incidents in the social domain. Most incidents in the post-test period occurred in the first year after testing. Only 15% of respondents knew where to complain officially if treated negatively because of genetics issues. Recommendations include the need for increased community and clinical education regarding genetic discrimination, for extended clinical genetics sector engagement and for co-ordinated monitoring, research and policy development at national levels in order for the full benefits of genetic testing technology to be realised.     

Comparing universal Lynch syndrome tumor-screening programs to evaluate associations between implementation strategies and patient follow-through

PurposeUniversal tumor screening (UTS) for all colorectal cancer patients can improve the identification of Lynch syndrome, the most common cause of hereditary colorectal cancer. This multiple-case study explored how variability in UTS procedures influenced patient follow-through (PF) with germ-line testing after a screen-positive result.MethodsData were obtained through Web-based surveys and telephone interviews with institutional informants. Institutions were categorized as Low-PF (≤10% underwent germ-line testing), Medium-PF (11–40%), or High-PF (>40%). To identify implementation procedures (i.e., conditions) unique to High-PF institutions, qualitative comparative analysis was performed.ResultsTwenty-one informants from 15 institutions completed surveys and/or interviews. Conditions present among all five High-PF institutions included the following: (i) disclosure of screen-positive results to patients by genetic counselors; and (ii) genetic counselors either facilitate physician referrals to genetics professionals or eliminate the need for referrals. Although both of these High-PF conditions were present among two Medium-PF institutions, automatic reflex testing was lacking and difficulty contacting screen-positive patients was a barrier. The three remaining Medium-PF and five Low-PF institutions lacked the conditions found in High-PF institutions.ConclusionMethods for streamlining UTS procedures, incorporating a high level of involvement of genetic counselors in tracking and communication of results and in reducing barriers to patient contact, are reviewed within a broader discussion on maximizing the effectiveness and public health impact of UTS.     

Pre‐test genetic counseling services for hereditary breast and ovarian cancer delivered by non‐genetics professionals in the state of Florida

Genetic counseling and testing for hereditary breast and ovarian cancer now includes practitioners from multiple healthcare professions, specialties, and settings. This study examined whether non‐genetics professionals (NGPs) perform guideline‐based patient intake and informed consent before genetic testing. NGPs offering BRCA testing services in Florida (n = 386) were surveyed about clinical practices. Among 81 respondents (response rate = 22%), approximately half reported: sometimes scheduling a separate session for pre‐test counseling lasting 11–30 min prior to testing, discussing familial implications of testing, benefits and limitations of risk management options, and discussing the potential psychological impact and insurance‐related issues. Few constructed a three‐generation pedigree, discussed alternative hereditary cancer syndromes, or the meaning of a variant result. This lack of adherence to guideline‐based practice may result in direct harm to patients and their family members. NGPs who are unable to deliver guideline adherent cancer genetics services should focus on identification and referral of at‐risk patients to in person or telephone services provided by genetics professionals.     

Differential use of available genetic tests among primary care physicians in the United States: results of a national survey

PurposeThis study assesses primary care physicians' experience ordering and referring patients for genetic testing, and whether minority-serving physicians are less likely than those serving fewer minorities to offer such services.MethodsSurvey of a random sample of 2000 primary care physicians in the United States (n = 1120, 62.3% response rate based on eligible respondents) conducted in 2002 to assess what proportion have (1) ever ordered a genetic test in general or for select conditions; (2) ever referred a patient for genetic testing to a genetics center or counselor, a specialist, a clinical research trial, or to any site of care.ResultsNationally, 60% of primary care physicians have ordered a genetic test and 74% have referred a patient for genetic testing. Approximately 62% of physicians have referred a patient for genetic testing to a genetics center/counselor or to a specialist, and 17% to a clinical trial. Minority-serving physicians were significantly less likely to have ever ordered a genetic test for breast cancer, colorectal cancer, or Huntington disease, or to have ever referred a patient for genetic testing relative to those serving fewer minorities.ConclusionsReduced utilization of genetic tests/referrals among minority-serving physicians emphasizes the importance of tracking the diffusion of genomic medicine and assessing the potential impact on health disparities.     

Genotype concordance and polygenic risk score estimation across consumer genetic testing data

The consumer genomics industry is steadily growing and delivering genetic information to over 10 million individuals. Yet, the implications of using data from different services remain unclear. We investigated the genotyped sites, concordance, and genetic risk estimation using data from three consumer services—two single nucleotide polymorphism (SNP)-array based and one sequencing based. In an N-of-one setting, we found the three services genotyped predominantly distinct sets of sites. While there was a high concordance between overlapping sites of the two SNP-array services (99.6%), there was a lower concordance between these services and a low-pass whole-genome service (73.0%). The discrepancy between the three sets of data resulted in different APOE genotypes and genetic risk scores of Alzheimer's disease. Our results demonstrate genotype results across consumer genomics platforms may lead to different genetic risk estimates, highlighting the need for careful quality control and interpretation.     

Characteristics associated with genetic counseling referral and BRCA1/2 testing among women in a large integrated health system

BackgroundEvidence shows underutilization of cancer genetics services. To explore the reasons behind this underutilization, this study evaluated characteristics of women who were referred for genetic counseling and/or had undergone BRCA1/2 testing.MethodsAn ovarian cancer risk perception study stratified 16,720 eligible women from the Henry Ford Health System into average-, elevated-, and high-risk groups based on family history. We randomly selected 3,307 subjects and interviewed 2,524 of them (76.3% response rate).ResultsAmong the average-, elevated-, and high-risk groups, 2.3, 10.1, and 20.2%, respectively, reported genetic counseling referrals, and 0.8, 3.3, and 9.5%, respectively, reported having undergone BRCA testing. Personal breast cancer history, high risk, and perceived ovarian cancer risk were associated with both referral and testing. Discussion of family history with a doctor predicted counseling referral, whereas belief that family history influenced risk was the strongest BRCA testing predictor. Women perceiving their cancer risk as much higher than other women their age were twice as likely (95% confidence interval: 2.0–9.6) to report genetic counseling referral.ConclusionIn a health system with ready access to cancer genetic counseling and BRCA testing, women who were at high risk underutilized these services. There were strong associations between perceived ovarian cancer risk and genetic counseling referral, and between a belief that family history influenced risk and BRCA testing.Genet Med advance online publication 19 June 2014     

Risk estimation for familial breast cancer: improving the system of counselling

Women with a family history of breast cancer dominate referrals for cancer genetic risk counselling across Europe. Given limited health care resources, managing this demand, while achieving good value for money for health services, is a major challenge. The paper reports the benefits and associated costs of moving from a traditional system of deriving family history of cancer during the patient's initial clinic attendance, to a protocol-driven system with pre-counselling assessment of family history. The evaluation was based on retrospective clinical data and a clinical audit. Changes in risk between referral and final risk assessment were ascertained and the cost difference between the two systems estimated. The study results showed that 14% of women assessed as 'low' genetic risk at referral were reassessed as 'moderate' or 'high' genetic risk for breast cancer following verification of family history. Sixteen per cent of those assessed as 'moderate' or 'high' genetic risk at referral were reassessed as 'low' genetic risk for breast cancer. Compared to the traditional system, the new protocol-driven system of risk assessment was more consistent, which reduced the number of return appointments and created time for clinicians to spend with other patients. The estimated cost of family history verification and genetic clinic appointment was calculated as 91.68 pounds (132.53 euro) per family history, compared to 104.00 pounds (150.34 euro) for the traditional system, representing a slight reduction in health service costs. Finally, the protocol-driven system can be used as part of ongoing audit for planning future genetics services in Scotland.     

Referral to cancer genetic counseling: are there stages of readiness?

As genetic awareness spreads among healthcare providers and the general public, and evidence mounts to show the efficacy of cancer control methods, referrals to cancer genetic counseling services for risk assessment are becoming more common. However, few studies have examined referral patterns to genetics and even less is known about referral uptake to clinical cancer genetic counseling. We investigated outcome of genetics referral in 43 affected women attending a breast cancer treatment program who were referred based on having BRCA mutation carrier risks > or =10%. Within 6 months, of the 36 women we were able to recontact, 13 (36%) came to an appointment at the cancer genetic counseling clinic (Acceptors), 10 (27%) said they intended to come in the future (Intenders), and 13 (36%) said they would not consider genetic counseling (Decliners). Referral uptake was framed by elements of the Transtheoretical model (TTM) to determine if decisional balance scores (DBSs), a summary of an individual's "Pro" and "Con" opinions related to genetic testing, correlated with their decision to follow through. Mean DBS's were strongly negative for the Decliner group (-7.4), weakly negative for the Intender group (-1.1), and positive for the Acceptor group (5.4). The difference in the DBS along the continuum was due more to the mean "Con" score decreasing, rather than the mean "Pro" score increasing. Theoretical frameworks are needed to study adherence to referral for cancer genetic counseling. Stage-based theories may have a role to play.     

Clinical genetics issues encountered by family physicians.

PURPOSE: To describe the genetics-related clinical issues encountered by family physicians, and the medical problems they referred to genetics consultants. METHODS: Questionnaires were mailed to a nationwide, random sample of 498 practicing family physicians, asking how many times in the past year they discussed genetic information about 19 familial or genetic conditions with patients and what proportion of the families with each genetic condition were referred for genetics consultation. Factor analysis was used to group the conditions. RESULTS: The response rate was 38% (n = 190). Respondents were similar to non-respondents except that more were women. Most family physicians reported discussing the genetics of common cancers, cardiovascular disease, and Alzheimer's disease with two or more patients in the past year. Thirteen percent had referred families for genetics assessment of breast-ovarian cancer but only two made genetics referrals for cardiovascular disease or dementia. 25% to 50% of family physicians had addressed genetic issues in at least one family with hemoglobinopathy, a blood clotting disorder, hemochromatosis, mental illness, vision loss or deafness, chromosome abnormality, infertility or pregnancy loss, congenital anomalies, mental retardation, and neurofibromatosis. Most cases were not referred to geneticists. Of respondents, 23% said that genetics consultation is very difficult to obtain or unavailable and 18% listed ethical and social dilemmas related to pursuing genetic diagnosis. CONCLUSION: Nationwide, family physicians address a variety of genetics issues with patients, most frequently consulting geneticists for perinatal conditions and familial cancers. Access to genetics consultation is more difficult in rural areas. These data may be used in organizing genetics services and in planning professional education programs for primary care clinicians.     

Direct to consumer genetic testing: a systematic review of position statements, policies and recommendations

In healthcare settings, genetic tests to determine whether an individual had inherited a genetic mutation are ordered by a health professional, and the results are interpreted and conveyed to the patient by that person. However, direct to consumer genetic testing (DTCGT) has enabled individuals to purchase genetic tests and receive results without the intervention of a health professional. To inform a set of guidelines for consumers and health professionals, we undertook a systematic review of position statements, policies and recommendations on the use of DTCGT. We performed a search of seven databases and the Internet for relevant documents. The search terms were 'direct to consumer' and 'genetic test', and documents in English published from 2002 to 2011 were included. The search retrieved 314 items, of which 14 were eligible for review. Five themes were derived from thematic analysis: motivation for use, potential benefits, potential harms, recommendations to guide consumers and need for research. The authors of these documents described more potential harms than benefits, but, although some stated that direct to consumer testing should be actively discouraged, others supported consumer rights to make autonomous choices. Further research into the impact of direct to consumer testing on health services and consumers is required to inform policies.     

AsktheGeneticistSM: five years of online experience

PurposeTo identify the genetic informational needs and assess the level of awareness about clinical genetic services among adults who use the internet.MethodsWe created an online service called AsktheGeneticist^SM (http://www.askthegen.org) to answer questions about medical genetics. Since 2003, we have received 4497 questions from every US state and 84 countries/territories. Genetic counselors draft answers to the questions submitted. The questions and answers are next reviewed by clinical geneticists, then organized by topic and uploaded to the site. A link to an online website-user satisfaction survey is e-mailed to the user with a link to their Q&A.ResultsBefore visiting AsktheGeneticist^SM, 20% (50/247) of survey respondents were unaware that genetic services existed. After visiting our website, 23.5% (58) of survey respondents sought contact with a genetics health care professional, compared with <1% of patients who self-refer to a general genetics clinic (binomial test; P < 0.0001). Website users most often sought information about a known genetic condition in their family and the risk of recurrence.ConclusionsOur data suggest that the internet can be an effective tool for increasing the awareness of genetic services and identifying genetic informational needs of online adults, as well as for connecting patients with genetic services.     

20-year experience on prenatal diagnosis in a reference university medical genetics center in Turkey

Background/aimAlthough cutting edge procedures such as cell-free fetal DNA isolation from maternal blood are now available, invasive prenatal tests are still being used extensively for prenatal diagnosis. The study aims to evaluate the demographic data, indications, and cytogenetic results of 9297 results of patients who underwent prenatal invasive testing for genetic analysis that were referred for the last 20 years in a University Medical Genetics Center.Materials and methodsThe records of 8363 amniocenteses, 626 chorionic villus, and 308 cordocenteses samples were retrospectively evaluated and analyzed regarding referral reasons, indications and their cytogenetic results. The total numbers and the percentages of each group were recorded; Chi-square and logistic regression analyses were performed to give the statistical likelihood of different events. ResultsThe number of referrals decreased significantly after 2009. Risk of having trisomy 21 as well as trisomy 13 and 18 significantly increased in parallel with advanced maternal age. When the 21–25 age group was compared to the older age groups in terms of having a trisomy 21 pregnancy, the risk doubled in the 36–40, 5 times higher in 41–45 and 10-fold in 46–50 age groups. No significant linear correlation between maternal serum screening test results and trisomy 21 was found, however the difference between the pregnancies whom cut-off value above and below 1/250 in maternal serum screening test were significant.ConclusionThese data have provided useful information on the frequency of referrals to the reference genetics department, and the feasibility of genetic services. By reviewing the indications and their corresponding results, we can offer invaluable insights that will be useful in genetic counseling and also in the development of more effective genetic strategies.     

Disclosing genetic information to family members without consent: Five Australian case studies

Genetic risk information is relevant to individual patients and also their blood relatives. Health practitioners (HPs) routinely advise patients of the importance of sharing genetic information with family members, especially for clinically actionable conditions where prevention is possible. However, some patients refuse to share genetic results with at-risk relatives, and HPs must choose whether to use or disclose genetic information without consent. This requires an understanding of their legal and ethical obligations, which research shows many HPs do not have. A recent UK case held that HPs have a duty to a patient's relatives where there is a proximate relationship, to conduct a balancing exercise of the benefit of disclosure of the genetic risk information to the relative against the interest of the patient in maintaining confidentiality. In Australia, there is currently no legal duty to disclose genetic information to a patient's at-risk relatives, but there are laws and guidelines governing unconsented use/disclosure of genetic information. These laws are inconsistent across different Australian states and health contexts, requiring greater harmonisation.Here we provide an up-to-date and clinically accessible resource summarising the laws applying to HPs across Australia, and outline five Australian case studies which have arisen in clinical genetics services, regarding the disclosure of genetic results to relatives without consent. The issues addressed here are relevant to any Australian HP with access to genetic information, as well as HPs and policy-makers in other jurisdictions considering these issues.     

A clinical and genetic analysis of multiple primary cancer referrals to genetics services

Multiple primary malignant tumours (MPMT) are frequently taken as an indicator of potential inherited cancer susceptibility and occur at appreciable frequency both among unselected cancer patients and, particularly, among referrals to cancer genetics services. However, there is a paucity of information on the clinical genetic evaluation of cohorts of MPMT patients representing a variety of tumour types. We ascertained a referral-based series of MPMT cases and describe the patterns of tumours observed. Service-based molecular genetic testing had demonstrated a pathogenic germline variant in an inherited cancer gene in fewer than one in four unselected referrals. To assess for evidence of thus far unidentified variants in those who tested negative, comparisons were made with those who tested positive. This revealed considerable overlap between the two groups with respect to clinical characteristics indicative of an inherited cancer syndrome. We therefore proceeded to test a subset of unexplained MPMT cases (n=62) for pathogenic germline variants in TP53 and PTEN but none were detected. Individuals with MPMT may receive negative genetic test results for a number of reasons, which are discussed. Many of these may be addressed by the increasing application of next generation sequencing techniques such as inherited cancer gene panels.     

The value of genetic testing: beyond clinical utility

ObjectiveTo assess the value of genetic testing from the perspective of the Department of Veterans Affairs (VA) clinical leadership.MethodsWe administered an Internet-based survey to VA clinical leaders nationwide. Respondents rated the value (on a 5-point scale) of each of six possible reasons for genetic testing. Bivariate and linear regressions identified associations between value ratings and environmental, organizational, provider, patient, and encounter characteristics.ResultsRespondents (n = 353; 63% response rate) represented 92% of VA medical centers. Tests that inform clinical management had the highest value rating (58.6%), followed by tests that inform disease prevention (56.4%), reproductive options (50.1%), life planning (43.9%), and a suspected (39.9%) or established (32.3%) diagnosis. Factors positively associated with high value included a culture that fosters adoption of genomics, specialist versus primary care provider, genetic tests available on laboratory menus, availability of genetic testing guidelines, clinicians knowing when to request genetics referrals, and availability of genetics professionals.ConclusionOur results demonstrate the varied value of genetic testing from the perspective of clinical leadership within a health-care system. Engaging organizational leadership in understanding the various reasons for genetic testing and its value beyond clinical utility may increase adoption of genetic tests to support patient-centered care.Genet Med advance online publication 15 December 2016     

Parents’ perceptions of genetics services for congenital heart disease: the role of demographic,clinical, and psychological factors in determining service attendance

PurposeWe sought to identify the demographic, clinical, and psychological factors associated with parents’ attendance at clinical genetics services for congenital heart disease.MethodsA survey assessing access to cardiac genetics services and a range of other variables was sent to the families of 213 children diagnosed with congenital heart disease between the years 2000 and 2009 at the Sydney Children’s Hospital, Australia.ResultsOf the 114 respondents, 22% had accessed cardiac genetics services. Variables strongly associated with service attendance included presence of a syndrome associated with congenital heart disease (odds ratio = 17.93; P < 0.001) and antenatal diagnosis of congenital heart disease (odds ratio = 4.13; P = 0.02). Most participants (87%) perceived genetic factors as “quite” or “extremely important” in the development of congenital heart disease, and many (73%) believed that receiving information about congenital heart disease and genetics was “quite” or “extremely important”; however, only 36% of participants could recall receiving information of this nature. Forty-two percent of parents reported current concerns about their child’s health, and a substantial subset reported levels of depression (26%), anxiety (27%), and stress (32%) warranting clinical attention.ConclusionThere is a strong desire among parents of children with congenital heart disease for greater information about the role of genetic factors; however, most families do not access cardiac genetics services and report limited recall of information gathered from other sources.Genet Med16 6, 460–468.     

The GRAIDS Trial: The development and evaluation of computer decision support for cancer genetic risk assessment in primary care

The development and evaluation of computer decision support for the assessment of cancer genetic risk in primary care is reported with two series of studies described: the RAGs (Risk Assessment in Genetics) studies and the GRAIDS (Genetic Risk Assessment in an Intranet and Decision Support) Trial. In the GRAIDS Trial, 45 general practices in Eastern England have been recruited and randomised. Comparison practices attend an educational session and receive clinical guidelines about familial breast and colorectal cancer. In the intervention practices a lead clinician is trained in cancer genetics and use of the GRAIDS software. The GRAIDS software is a simple pedigree-drawing program that implements clinical guidelines for familial breast and colorectal cancer and presents individualised information about breast cancer risk in a range of formats. Outcome measures of the trial include: frequency of software use, practitioners’ attitudes towards the software, total number of referrals to secondary care about familial cancer and the proportion that meet regional referral criteria, and a patient-centred measure of informed decision making. The family history will become an increasingly important tool in primary care to assess genetic risk. This research evaluates an approach to support high-quality advice about cancer genetics in primary care which could be applied more broadly as our understanding of complex disease genetics increases.     

The GRAIDS Trial: the development and evaluation of computer decision support for cancer genetic risk assessment in primary care

The development and evaluation of computer decision support for the assessment of cancer genetic risk in primary care is reported with two series of studies described: the RAGs (Risk Assessment in Genetics) studies and the GRAIDS (Genetic Risk Assessment in an Intranet and Decision Support) Trial. In the GRAIDS Trial, 45 general practices in Eastern England have been recruited and randomised. Comparison practices attend an educational session and receive clinical guidelines about familial breast and colorectal cancer. In the intervention practices a lead clinician is trained in cancer genetics and use of the GRAIDS software. The GRAIDS software is a simple pedigree-drawing program that implements clinical guidelines for familial breast and colorectal cancer and presents individualised information about breast cancer risk in a range of formats. Outcome measures of the trial include: frequency of software use, practitioners' attitudes towards the software, total number of referrals to secondary care about familial cancer and the proportion that meet regional referral criteria, and a patient-centred measure of informed decision making. The family history will become an increasingly important tool in primary care to assess genetic risk. This research evaluates an approach to support high-quality advice about cancer genetics in primary care which could be applied more broadly as our understanding of complex disease genetics increases.