DTC genetic testing: pendulum swings and policy paradoxes

Caulfield T. DTC genetic testing: pendulum swings and policy paradoxes. After decades of optimistic portrayals, there has been a shift in the way that the popular press represents genomic research. A skeptical view has become more common. The central reason for this pendulum swing away from popular support is the harsh truth that most genetic risk information just isn't that predictive. This reality has created a fascinating policy paradox. If, as many in the scientific community are now saying, genetic information is not the oracle of our future health as we were once led to believe, and if access does not, for most, cause harm, why regulate the area? Why worry about shoddy direct‐to‐consumer (DTC) genetic testing companies? One primary justification, and one endorsed by the recent Canadian College of Medical Geneticists (CCMG) Policy Statement on DTC Genetics Testing, is that information that is conveyed to the public about genetics via marketing and to those who access DTC tests should, at a minimum, be accurate.     

Genetics professionals are key to the integration of genetic testing within the practice of frontline clinicians

PurposeGenetic 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).MethodsWe 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.ResultsThe 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.ConclusionMost 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.     

Eliciting preferences for priority setting in genetic testing: a pilot study comparing best-worst scaling and discrete-choice experiments

Given the increasing number of genetic tests available, decisions have to be made on how to allocate limited health-care resources to them. Different criteria have been proposed to guide priority setting. However, their relative importance is unclear. Discrete-choice experiments (DCEs) and best-worst scaling experiments (BWSs) are methods used to identify and weight various criteria that influence orders of priority. This study tests whether these preference eliciting techniques can be used for prioritising genetic tests and compares the empirical findings resulting from these two approaches. Pilot DCE and BWS questionnaires were developed for the same criteria: prevalence, severity, clinical utility, alternatives to genetic testing available, infrastructure for testing and care established, and urgency of care. Interview-style experiments were carried out among different genetics professionals (mainly clinical geneticists, researchers and biologists). A total of 31 respondents completed the DCE and 26 completed the BWS experiment. Weights for the levels of the six attributes were estimated by conditional logit models. Although the results derived from the DCE and BWS experiments differed in detail, we found similar valuation patterns in the DCE and BWS experiments. The respondents attached greatest value to tests with high clinical utility (defined by the availability of treatments that reduce mortality and morbidity) and to testing for highly prevalent conditions. The findings from this study exemplify how decision makers can use quantitative preference eliciting methods to measure aggregated preferences in order to prioritise alternative clinical interventions. Further research is necessary to confirm the survey results.     

Mexican geneticists’ views of ethical issues in genetics testing and screening. Are eugenic principles involved?

Herein we discuss Mexican geneticists' views of ethical issues in genetic testing and screening, analyzing whether eugenic principles are involved in this activity. The information was obtained from a comprehensive survey on genetics, ethics, and society organized by Wertz and Fletcher in 1993, in which 37 nations participated. The responses to 21 questions from 64 out of 89 (72%) geneticists invited to participate are analyzed in this paper. The questions were practically the same as those answered recently by a group of Chinese geneticists (Mao X. Chinese geneticists' views of ethical issues in genetic testing and screening: evidence for eugenics in China. Am J Hum Genet 1998: 63: 688-695), who work in a country where the furtherance of eugenic principles is considered to be the goal of human genetics. We concluded that although there are many similarities in the answers from both countries, this is not indicative of Mexican geneticists pursuing eugenic goals because: a) there is no coercion involved; and b) there is no intention of improving the gene pool.     

Knowledge of genetics and attitudes toward genetic testing in two hereditary ataxia (SCA 1) Kindreds

Molecular genetic predictive or prenatal genetic testing is now possible in families with one form of adult-onset, autosomal dominant ataxia (SCA 1). Before the SCA 1 gene was isolated, we began a study of the knowledge of genetics, the perception of the disease, and the intended use of genetic testing among members of two large SCA 1 kindreds. Questionnaires were sent to 210 consenting affected, at-risk, and spouse members of two SCA 1 kindreds; data from the 117 respondents were analyzed on a personal computer. Sixty-nine percent of respondents thought predictive testing (by genetic linkage) should be made available immediately, and 42% thought prenatal testing should be made available. The kindreds differed in several important aspects: knowledge of genetic concepts, family size, and anticipated emotional responses to genetic testing. No respondent had obtained individualized genetic counseling. There is moderate interest in genetic testing for this fatal neurodegenerative disease of adulthood. Members of our kindreds have not received genetic counseling outside of the research setting. Finally, factors specific to a particular kindred may influence or predict individual responses to genetic testing. © 1994 Wiley-Liss, Inc.     

GeneTests-GeneClinics: genetic testing information for a growing audience

The development and usage of two companion NIH-funded genetic testing information databases, GeneTests (www.genetests.org) and GeneClinics (www.geneclinics.org), now merged into one web site, reflect the steadily increasing use of genetic testing and the expanding audience for genetic testing information. Established in 1993 as Helix, a genetics laboratory directory of approximately 110 listings, GeneTests has grown into a database of over 900 tests for inherited diseases, a directory of over 500 international laboratories, a directory of over 1,000 U.S. and international genetics clinics, and a resource for educational/teaching materials and reports of summary genetic test data. GeneClinics, founded in 1997 as an expert-authored, peer-reviewed, disease-specific knowledge base relating genetic testing to patient care, has grown steadily, now containing over 130 expert-authored, peer-reviewed full-text entries relating genetic testing information to diagnosis, management, and genetic counseling of specific inherited diseases. In spring 2001 the two databases were merged and in October 2001 the two web sites were merged for the purpose of seamless navigation into the GeneTests-GeneClinics site (www.genetests.org or www.geneclinics.org); the GeneClinics knowledge base was renamed "GeneReviews" to avoid confusion with the U.S. and international clinic directories. As genetic testing has moved steadily out of research venues and into routine medical practice, the user audience for these databases has become international and expansive and includes healthcare providers, patients, educators, policy makers, and the media. The use of these combined resources has grown to approximately 3,200 visits/day.     

Public interest in predictive genetic testing, including direct-to-consumer testing, for susceptibility to major depression: preliminary findings

The past decade has seen rapid advances in the identification of associations between candidate genes and a range of common multifactorial disorders. This paper evaluates public attitudes towards the complexity of genetic risk prediction in psychiatry involving susceptibility genes, uncertain penetrance and gene–environment interactions on which successful molecular-based mental health interventions will depend. A qualitative approach was taken to enable the exploration of the views of the public. Four structured focus groups were conducted with a total of 36 participants. The majority of participants indicated interest in having a genetic test for susceptibility to major depression, if it was available. Having a family history of mental illness was cited as a major reason. After discussion of perceived positive and negative implications of predictive genetic testing, nine of 24 participants initially interested in having such a test changed their mind. Fear of genetic discrimination and privacy issues predominantly influenced change of attitude. All participants still interested in having a predictive genetic test for risk for depression reported they would only do so through trusted medical professionals. Participants were unanimously against direct-to-consumer genetic testing marketed through the Internet, although some would consider it if there was suitable protection against discrimination. The study highlights the importance of general practitioner and public education about psychiatric genetics, and the availability of appropriate treatment and support services prior to implementation of future predictive genetic testing services.     

Direct-to-consumer genomic testing: systematic review of the literature on user perspectives

Genetic tests have traditionally been offered by health professionals. However, genomic tests have been available direct to the consumer for the last decade, increasingly via the Internet. The aim of this systematic review was to ascertain the evidence concerning use of direct-to-consumer genomic testing from the consumer perspective. Primary research was identified using the search terms 'direct-to-consumer' and 'genomic or genetic' in six bibliographic databases and citation searching of findings. In all, 17 papers were reviewed: 3 qualitative and 14 quantitative. Findings indicate a low level of awareness of direct-to-consumer genomic testing and, because of the hypothetical nature of many studies, little evidence from users of such tests. Although potential users appear to be interested in information about their risks of developing common diseases, concerns were expressed about privacy of genetic risk information and the reliability of genomic tests. Consumers were anxious about the nature of the results. There appeared to be a preference to access genomic tests via a health professional, or to discuss the results and obtain advice from a health professional. Authors of only two papers recruited participants who had used direct-to-consumer tests and samples from the large quantitative studies were not representative of the population. These factors limit the value of the available evidence. However, we conclude that there is public interest in direct-to-consumer genomic tests, and that this is likely to result in an increased workload for a range of health professionals. We also consider that there are educational implications for both consumers and health professionals.     

Are the kids really all right? Direct-to-consumer genetic testing in children: are company policies clashing with professional norms?

The genetic testing of minors within the direct-to-consumer (DTC) genetic testing (GT) context has been given relatively little attention. The issue of testing healthy children for diseases that would only develop in adulthood raises many important ethical, legal and social issues. As genetic testing is now available outside of the traditional health care system, often without even the intermediate of a health care professional, we surveyed 37 DTC GT companies regarding their policies for testing in children. Although the response rate is relatively low (35%, 13/37), our findings reveal that a clear majority of companies do perform genetic testing in minors. As such, companies testing for adult onset diseases are acting in contradiction of established professional guidelines, which state, among others, that, for predictive genetic testing, the availability of therapeutic or preventive measures is necessary for testing to be performed in asymptomatic minors. The community of stakeholders in children's health care and genetic testing should, therefore, decide which standards need to be upheld by DTC GT companies and ensure that these are met.     

The composition and capacity of the clinical genetics workforce in high-income countries: a scoping review

As genetics becomes increasingly integrated into all areas of health care and the use of complex genetic tests continues to grow, the clinical genetics workforce will likely face greatly increased demand for its services. To inform strategic planning by health-care systems to prepare to meet this future demand, we performed a scoping review of the genetics workforce in high-income countries, summarizing all available evidence on its composition and capacity published between 2010 and 2019. Five databases (MEDLINE, Embase, PAIS, CINAHL, and Web of Science) and gray literature sources were searched, resulting in 162 unique studies being included in the review. The evidence presented includes the composition and size of the workforce, the scope of practice for genetics and nongenetics specialists, the time required to perform genetics-related tasks, case loads of genetics providers, and opportunities to increase efficiency and capacity. Our results indicate that there is currently a shortage of genetics providers and that there is a lack of consensus about the appropriate boundaries between the scopes of practice for genetics and nongenetics providers. Moreover, the results point to strategies that may be used to increase productivity and efficiency, including alternative service delivery models, streamlining processes, and the automation of tasks.     

Predictive,pre-natal and diagnostic genetic testing for Huntington's disease: the experience in Canada from 1987 to 2000

Predictive and pre-natal testing for Huntington's Disease (HD) has been available since 1987. Initially this was offered by linkage analysis, which was surpassed by the advent of the direct mutation test for HD in 1993. Direct mutation analysis provided an accurate test that not only enhanced predictive and pre-natal testing, but also permitted the diagnostic testing of symptomatic individuals. The objective of this study was to investigate the uptake, utilization, and outcome of predictive, pre-natal and diagnostic testing in Canada from 1987 to April 1, 2000. A retrospective design was used; all Canadian medical genetics centres and their affiliated laboratories offering genetic testing for HD were invited to participate. A total of 15 of 22 centres (68.2%), currently offering or ever having offered genetic testing for HD, responded, providing data on test results, demographics, and clinical history. A total of 1061 predictive tests, 15 pre-natal tests, and 626 diagnostic tests were performed. The uptake for predictive testing was approximately 18% of the estimated at-risk Canadian population, ranging from 12.5% in the Maritimes to 20.7% in British Columbia. There appears to have been a decline in the rate of testing in recent years. Of the predictive tests, 45.0% of individuals were found to have an increased risk, and a preponderance of females (60.2%) sought testing. A greater proportion of those at < or = 25% risk sought predictive testing once direct CAG mutation analysis had become available (10.9% after mutation analysis vs 4.7% before mutation analysis, p = 0.0077). Very few pre-natal tests were requested. Of the 15 pre-natal tests, 12 had an increased risk, resulting in termination of pregnancy in all but one. Diagnostic testing identified 68.5% of individuals to be positive by mutation analysis, while 31.5% of those with HD-like symptoms were not found to have the HD mutation. The positive diagnostic tests included 24.5% of individuals with no known prior family history of HD.     

eyeGENE®: a vision community resource facilitating patient care and paving the path for research through molecular diagnostic testing

Molecular genetics and genomics are revolutionizing the study and treatment of inherited eye diseases. In recognition of the impact of molecular genetics on vision and ophthalmology, the National Eye Institute established the National Ophthalmic Disease Genotyping and Phenotyping Network (eyeGENE®) as a multidirectional research initiative whereby a clinical component for patients diagnosed with inherited eye disease fosters research into the causes and mechanisms of these ophthalmic diseases. This is accomplished by broadening access to genetic diagnostic testing and maintaining a repository of DNA samples from clinically characterized individuals and their families to allow investigations of the causes, interventions, and management of genetic eye disorders. The eyeGENE® Network currently includes Clinical Laboratory Improvement Amendments (CLIA)‐certified diagnostic laboratory partners, over 270 registered clinical organizations with 500 registered users from around the United States and Canada, and is now testing approximately 100 genes representing 35 inherited eye diseases. To date, the Network has received 4400 samples from individuals with rare inherited eye diseases, which are available for access by the vision research community. eyeGENE® is a model partnership between the U.S. federal government, eye health care providers, CLIA‐approved molecular diagnostic laboratories, private industry, and scientists who represent a broad research constituency.     

Genetic information leaflets: influencing attitudes towards genetic testing.

PURPOSE: This article explores how a "neutral" genetics information leaflet influenced people's attitudes to be more positive toward predictive genetic testing. This is of concern, given the desire within clinical genetics and population based testing to provide information that informs choice without directing toward, or against, testing. METHOD: Four studies are reported. The first two investigated presentation (glossy and colored vs. black and white), and method of reading (read only vs. read followed by probing questions). The second two investigated content, using "think aloud," "card sort," and delayed recall tasks. RESULTS: Those receiving a glossy leaflet expressed more positive attitudes and more interest in undergoing testing than those receiving a black and white leaflet, and those who were asked questions about what they had read were more positive about genetic testing than those who only read the leaflet. Recall one week later varied from 72% to 28%, depending on type of information. Information that described the advantages of genetic testing or discussed genes and genetic testing in relation to disease were well recalled and rated positively. Attitudes toward information ranged from 100% positive (e.g., what diseases genetic tests are available for) to 0% positive (e.g., the meaning of a positive result). CONCLUSION: These results show that quite small changes within a leaflet can change attitudes toward genetic testing. This is of concern, given the association between attitudes toward a behavior and undergoing that behavior. The form, method of presentation, and content of genetic information leaflets should be evaluated for impact on attitude and decisions before they are used clinically.     

Removing the shadow of the law from the debate about genetic testing of children

When physicians view efforts to obtain genetic testing for children as unwise or contrary to the children's interests, they face difficult problems both of ethics and of communicating with the parents. Contrary to the suggestions of some, the law has little to say about how physicians resolve these dilemmas. Parents do not have a constitutionally protected right to demand that unwilling physicians perform these tests. In addition, there is little risk of liability for damages unless the child suffers physical harm as a result of the physician's refusal to do the test. The debate about genetic testing of children needs to take place with a clear understanding of the law's limited impact. © 1995 Wiley-Liss, Inc.     

Novel LAMB3 mutations cause non‐syndromic amelogenesis imperfecta with variable expressivity

The field of genetics is evolving rapidly, significantly expanding the number of clinically useful genetic tests. The cost of genetic testing has created an increasing burden on public health care budgets. In Canada, funding bodies have responded by developing independent systems. Key individuals in each province and territory participated in a semi‐structured interview regarding the process in their jurisdiction to approve funding for referred out genetic testing and their decision‐making criteria. Two themes were identified: the importance of clinical utility in decision‐making and the utilization of genetic specialists as gate keepers. Allocation of a specific budget appears to be associated with some fiscal responsibility. Collaboration between provincial and territorial bodies may lead to a more unified approach across Canada.     

An evaluation of clinical presentation and genetic testing approaches for patients with neuromuscular disorders

Inherited neuromuscular disorders (NMDs) are a large group of genetic conditions characterized by impaired peripheral nerve, motor neuron, neuromuscular junction, or skeletal muscle function. These conditions are also known to have clinical and genetic heterogeneity and variable ages of onset. Clinical evaluation for NMDs has increasingly incorporated molecular genetics. However, genetic testing is complicated by the variety of testing options and the ambiguity of NMD phenotypes. Examining test selection and yield may elucidate testing recommendations and improve the diagnostic journey for these patients. This retrospective chart review evaluated the clinical presentations, genetic testing approaches, and diagnostic outcomes of 155 patients with suspected NMDs at Cincinnati Children's Hospital Medical Center. A total of 262 individual tests were ordered, averaging 1.7 tests per patient. The clinic utilized 26 separate genetic tests, with test yields ranging from 0% to 66%. Overall, 21% of patients received a genetic diagnosis. Of all the clinical findings evaluated, elevated CPK levels with or without muscle weakness were the most informative symptoms correlated with a diagnostic result. This study highlights several genetic testing considerations for NMDs, including the variability of diagnostic outcomes. This knowledge is relevant to clinicians and patients, especially during the pretest counseling and consenting process.     

Legislation on direct-to-consumer genetic testing in seven European countries

An increasing number of private companies are now offering direct-to-consumer (DTC) genetic testing services. Although a lot of attention has been devoted to the regulatory framework of DTC genetic testing services in the USA, only limited information about the regulatory framework in Europe is available. We will report on the situation with regard to the national legislation on DTC genetic testing in seven European countries (Belgium, the Netherlands, Switzerland, Portugal, France, Germany, the United Kingdom). The paper will address whether these countries have legislation that specifically address the issue of DTC genetic testing or have relevant laws that is pertinent to the regulatory control of these services in their countries. The findings show that France, Germany, Portugal and Switzerland have specific legislation that defines that genetic tests can only be carried out by a medical doctor after the provision of sufficient information concerning the nature, meaning and consequences of the genetic test and after the consent of the person concerned. In the Netherlands, some DTC genetic tests could fall under legislation that provides the Minister the right to refuse to provide a license to operate if a test is scientifically unsound, not in accordance with the professional medical practice standards or if the expected benefit is not in balance with the (potential) health risks. Belgium and the United Kingdom allow the provision of DTC genetic tests.