Analysis of state laws on informed consent for clinical genetic testing in the era of genomic sequencing

This article assesses the adequacy of informed consent to clinical genetic testing laws based on an examination of 15 states with institutions that had been involved in a National Institutes of Health-supported Clinical Sequencing Exploratory Research Consortium project. We identified relevant statutory provisions through a legal search engine and included statutes that describe the informed consent requirements for clinical genetic testing and/or the protections for genetic material, information, or data. We found that statutory definitions were often limited in problematic ways, such as focusing only on variants known to be associated with disease or negative health effects or associated with asymptomatic disease. Some statutes required complex levels of detail if applied to genomic technologies and set confusing disclosure standards for current use and future access. Others had exceptions from informed consent requirements for future research use, limited requirements for the destruction of specimens as opposed to derived data, or linked key definitional components to the evolving concept of “identifiability.” Further reform and research are needed to ensure that state law protections advance as rapidly as the science they aspire to enable.     

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

PurposeThe 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.MethodsBRCA1/2-negative and untested patients completed pre- and posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing.ResultsOf 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. Thirty-three 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.ConclusionSome patients, particularly those without prior BRCA1/2 testing, decline multiplex testing. Most patients who proceeded with testing did not experience negative psychological responses, but larger studies are needed. The tiered-binned approach is an innovative genetic counseling and informed consent model for further study in the era of multiplex testing.     

Testing for inherited susceptibility to breast cancer: A survey of informed consent forms for BRCA1 and BRCA2 mutation testing

The identification of genetic mutations linked to breast cancer has made it possible to test for the genetic predisposition to this disease. However, though this test may provide certain benefits, there are also potential risks involved with the testing process, including social and economic considerations. In light of these potential risks, we sought to determine what information individuals are receiving in the informed decision making process. To learn the minimal amount of information the actual testees receive, we obtained 10 informed consent forms from seven different testing facilities. These testing centers include the major sources of BRCA1 and BRCA2 mutation testing in the United States at this time. We analyzed the content of these forms by developing content categories and scoring them appropriately. We found all ten forms discussed in varying ways and to varying degrees the purpose of genetic testing, limitations of the test, implications of both positive and negative results, and confidentiality procedures; most, but not all, addressed various psychological and insurance risks. Overall, the forms demonstrated substantial variation in content and organization, underlining the need for more discussion and research on the purpose, nature, and effectiveness of informed consent forms for this type of genetic test. Am. J. Med. Genet. 75:82–87, 1998. © 1998 Wiley-Liss, Inc.     

Comparison of group counseling with individual counseling in the comprehension of informed consent: a randomized controlled trial

Background  

Studies on different methods to supplement the traditional informed consent process have generated conflicting results. This study was designed to evaluate whether participants who received group counseling prior to administration of informed consent understood the key components of the study and the consent better than those who received individual counseling, based on the hypothesis that group counseling would foster discussion among potential participants and enhance their understanding of the informed consent.     

Consumers' use of web-based information and their decisions about multiplex genetic susceptibility testing

Background

Few data exist to inform concerns raised by online direct-to-consumer marketing of genetic susceptibility tests, such as those offered by commercial entities like 23andme, Navigenics, and DNA Direct. The Multiplex Initiative, a population-based study of healthy adults, provides the first opportunity to evaluate how use of a Web-based decision tool that conveyed information about a genetic susceptibility test influenced individuals’ test decisions.

Objective

To inform the ongoing debate over whether individuals offered genetic susceptibility testing without the involvement of a health care provider (eg, through direct-to-consumer testing) can make informed decisions about testing when guided by online decision aids.

Methods

Participants were 526 members of a large health maintenance organization aged 25 to 40 years old who visited a study website. Multivariate logistic regression models were tested to examine the association of website usage with downstream test decisions.

Results

Participants viewed an average of 2.9 of the 4 pages introducing the multiplex test, 2.2 of the 8 pages describing the health conditions, and 3.2 of the 15 pages describing the genes. For each page viewed, participants were more likely to describe their decision-making as easy (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.01-1.07) and to decide to be tested (OR 1.08, 95% CI 1.05-1.11).

Conclusions

Healthy adults in this study perceived Web-based genomic information presented using evidence-based communications approaches to be helpful in supporting both decisions to test and not to test. Continued research is needed to ensure that these results generalize to target groups with lower literacy and less Internet savvy.     

US physicians' attitudes toward genetic testing for cancer susceptibility

Genetic testing for an inherited susceptibility to cancer is an emerging technology in medical practice. Little information is currently available about physicians' attitudes toward these tests. To assess US physicians' opinions on unresolved issues surrounding genetic testing, a 15-min survey was administered to a stratified random sample of 1,251 physicians from 8 specialties, selected from a file of all licensed physicians in the US (response rate = 71.0%). Dependent measures included physicians' attitudes toward genetic counseling and testing qualifications, availability of guidelines, patient confidentiality and insurance discrimination issues, and clinical utility of genetic tests. More than 89% of physicians reported a need for physician guidelines, 81% thought that patients with positive genetic test results are at risk for insurance discrimination, and more than 53% thought that it was difficult to ensure the confidentiality of test results. Almost 25% indicated that genetic tests for cancer susceptibility have too many inaccurate or ambiguous results; nearly 75% thought that clear guidelines are not available for managing patients with positive test results. Only 29% of physicians reported feeling qualified to provide genetic counseling to their patients. More than 84% of oncologists considered themselves qualified to recommend genetic testing to their patients compared with 40% of primary care physicians (PCPs), and 57% of tertiary care physicians (TCPs). US physicians expressed great uncertainty about issues surrounding genetic testing for cancer susceptibility. Results of this national survey underscore the need to provide physicians with clear guidelines on the use of genetic cancer susceptibility tests and effective medical training on their appropriate implementation.     

Understanding of informed consent by parents of children enrolled in a genetic biobank

PurposePrior research suggests that parents undervalue long-term risks associated with their children’s participation in research studies. The primary aim of this study was to evaluate parental understanding of informed consent for a pediatric biobanking study.MethodsThe study population included parents who provided consent for their child to participate in a study examining the genetic etiology of congenital cardiovascular malformations. Informed consent understanding was measured by adapting the Quality of Informed Consent assessment to our study. We evaluated possible predictors of individual Quality of Informed Consent items using generalized estimating equations.ResultsA total of 252 individuals representing 188 families completed the study. The Quality of Informed Consent items best understood by parents included consent to participate in research, the main purpose of the study, and the possibility of no direct benefit. The items least understood by parents were those involving the indefinite storage of DNA, the possible risks of participation, and the fact that the study was not intended to treat their child’s heart defect. Parent age and medical decision making by one versus both parents were frequent predictors of individual Quality of Informed Consent items.ConclusionParents overestimate personal benefit and underestimate the risks associated with their child’s participation in a biobanking study.Genet Med16 2, 141–148.     

Population-based genetic testing of asymptomatic women for breast and ovarian cancer susceptibility

PurposeThe identification of carriers of hereditary breast and ovarian cancer (HBOC) gene variants through family cancer history alone is suboptimal, and most population-based genetic testing studies have been limited to founder mutations in high-risk populations. Here, we determine the clinical utility of identifying actionable variants in a healthy cohort of women.MethodsGermline DNA from a subset of healthy Australian women participating in the lifepool project was screened using an 11-gene custom sequencing panel. Women with clinically actionable results were invited to attend a familial cancer clinic (FCC) for post-test genetic counseling and confirmatory testing. Outcomes measured included the prevalence of pathogenic variants, and the uptake rate of genetic counseling, risk reduction surgery, and cascade testing.ResultsThirty-eight of 5908 women (0.64%) carried a clinically actionable pathogenic variant. Forty-two percent of pathogenic variant carriers did not have a first-degree relative with breast or ovarian cancer and 89% pursued referral to an FCC. Forty-six percent (6/13) of eligible women pursued risk reduction surgery, and the uptake rate of cascade testing averaged 3.3 family members per index case.ConclusionWithin our cohort, HBOC genetic testing was well accepted, and the majority of high-risk gene carriers identified would not meet eligibility criteria for genetic testing based on their existing family history.     

Barriers to participating in genetic counseling and BRCA testing during primary treatment for breast cancer

PurposeLittle is known about reasons why eligible breast cancer patients decline BRCA mutation testing. They may withdraw at different stages during genetic counseling for different reasons. We prospectively studied perceived benefits and barriers to genetic counseling and BRCA testing in 102 newly diagnosed breast cancer patients approached for genetic counseling at the start of radiotherapy.MethodsPatients completed questionnaires and participated in interviews at different stages of the counseling protocol.ResultsParticipation was not influenced by distress, knowledge about hereditary breast cancer, previous genetic testing in relatives, or perceived risks and barriers. Immediate decliners (n = 23) do not believe genetic testing is relevant for them. Patients who decline after pedigree compilation (n = 14) are more hesitant and anxious about the influence of the test result on their future often wishing to postpone further testing. Late decliners (n = 7) withdraw afraid of the test result and/or after a relative's objection. These decliners are not easily identified upon approach because they are similar to patients who receive a DNA test result (n = 58). Notwithstanding their decline, 81% agreed to the timing or would have preferred an earlier approach for genetic counseling.ConclusionDecliners may make more informed decisions after tailored health education, including adequate risk information.     

Anticipated reactions to genetic testing for hereditary non-polyposis colorectal cancer susceptibility

Genetic testing for cancer susceptibility (e.g. hereditary non-polyposis colorectal cancer) is available for some families with a history of colon cancer. Our aim was to investigate participants' anticipated emotional and behavioral reactions to genetic testing for colon cancer and whether gender or clinical risk influences these reactions. 437 asymptomatic participants with a colorectal cancer family history completed a questionnaire about anticipated emotions and actions, under different genetic testing scenarios. More women than men anticipated feeling worried, regretful, and angry if tested positive. People at lower-risk anticipated more surprise and disbelief than those at higher-risk. People anticipated feeling more guilt, regret and less relief if they were not tested than if they were. High-risk results were anticipated to increase depression and worry. Most people still wanted screening if at low risk, anticipated leading healthier lifestyles whatever the result, but would make more plans for the future if they were at high risk. Clinical implications are that as anticipated emotional effects of not being tested may be more severe than having a test, people choosing to forgo testing should feel able to reconsider their decision anytime. Most people did not anticipate strong emotional reactions but thought it would change their lifestyle and would like continued clinical surveillance whatever the result.     

Education about genetic testing for breast cancer susceptibility: patient preferences for a computer program or genetic counselor

The purpose of this study was to describe and compare patient preferences for a genetic counselor or an interactive computer program for various components of genetic education and counseling for breast cancer susceptibility. As part of a randomized intervention study on genetics education and counseling for breast cancer risk, 29 women at moderate risk were educated by both a genetic counselor and an interactive computer program. After both educational interventions, participants completed Likert-style and open-ended questionnaires about what they liked most and least about each intervention, and whether they preferred the counselor or computer for a variety of tasks. Participants were largely satisfied with both the computer program and the genetic counselor. A majority preferred the genetic counselor for addressing their concerns, discussing options and alternatives, being sensitive to emotional concerns, helping to make a decision, being a good listener, assuring understanding, helping to make a good choice, helping to understand genes and breast cancer, telling them what they needed to know, being respectful, setting a relaxed tone, and putting them at ease. However, a majority of the women either preferred the computer program or were neutral about allowing patients to learn at their own pace, helping to avoid embarrassment, making good use of time, explaining genes and breast cancer, and treating the patient as an adult. Qualitative analysis of open-ended questions affirmed that patients valued the personal interactions with the counselors, and liked having their specific questions answered. They liked that the computer was self-paced, informative and private, and could be used without causing embarrassment. We concluded that a computer literate, mostly white group of women at moderate risk for inherited susceptibility to breast cancer preferred interacting with a genetic counselor for personal, individualized components of the genetic counseling process, but accepted or preferred a computer program for being self-paced, private, and informative. By incorporating such a computer program into the genetic education process, it is possible that genetic counselors would be able to spend more time performing the personal, individualized components of genetic counseling.     

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.     

Communication and technology in genetic counseling for familial cancer

When a cancer predisposing germline mutation is detected in an index case, the presence of the underlying syndrome is confirmed and the potential for predictive testing of at‐risk relatives is established. However, the reporting of a positive family history does not routinely lead to communication of information about risk to close, much less distant relatives. This review summarizes information technology utilized to address penetration or ‘reach’ of knowledge of risk within extended families, including the use of telephone and video counseling to reach distant patients, and anticipate novel internet‐based processes for communication between investigators and relatives.     

Eligibility criteria in private and public coverage policies for BRCA genetic testing and genetic counseling

PurposeCoverage policies for genetic services for hereditary cancers are of interest because the services influence cancer risk reduction for both persons with cancer and their family members. We compared coverage policies for BRCA genetic testing and genetic counseling among selected payers in the United States to illuminate eligibility criteria variation that may explain differential access by insurance type. We compared these policies with policies for breast cancer screening with magnetic resonance imaging to consider whether payers apply a unique policy approach to genetic services.MethodsWe conducted a case study of large private and public payers selected on number of covered lives. We examined coverage policies for BRCA genetic testing, genetic counseling, and screening with magnetic resonance imaging and the eligibility criteria for each. We compared eligibility criteria against National Comprehensive Cancer Network guidelines.ResultsEligibility criteria for BRCA testing were related to personal history and family history of cancer. Although private payers covered BRCA testing for persons with and without cancer, the local Medicare carrier in our study only covered testing for persons with cancer. In contrast, Arizona's Medicaid program did not cover BRCA testing. Few payers had detailed eligibility criteria for genetic counseling. Private payers have more detailed coverage policies for both genetic services and screening with magnetic resonance imaging in comparison with public payers.ConclusionDespite clinical guidelines establishing standards for BRCA testing, we found differences in coverage policies particularly between private and public payers. Future research and policy discussions can consider how differences in private and public payer policies influence access to genetic technologies and health outcomes.