Perspectives of clinical genetics professionals toward genome sequencing and incidental findings: a survey study

The introduction of clinical genome‐wide sequencing raises complex issues regarding the management of incidental findings. However, there is a lack of empirical studies assessing views of providers involved in potential disclosure of such findings. In an anonymous survey of 279 clinical genetics professionals, we found that the vast majority of participants agreed that they were interested in knowing about clinically actionable incidental findings in themselves (96%) and their child (99%), and they reported that these types of findings should be disclosed in adult (96%) and minor (98%) patients. Approximately three‐fourths agreed that they were personally interested in knowing about an adult‐onset clinically actionable disease (78%) and a childhood‐onset non‐clinically actionable disease (75%) in their child. A similar percentage of participants (70%) felt that these two types of findings should be disclosed to patients. Forty‐four percent of participants wanted to know about an incidental finding that indicates an adult‐onset non‐clinically actionable condition in themselves and 31% wanted to know about this type of information in their child. Findings from this study revealed participants' views highly dependent on clinical actionability. Further research is needed with a broader population of geneticists to increase generalizability, and with diverse patients to assess their perspectives about results disclosure from clinical sequencing.     

Attitudes toward the right to autonomous decision‐making in psychiatric genetic testing: Controversial and context‐dependent

Recent breakthroughs in psychiatric genetics have identified genetic risk factors of yet unknown clinical value. A main ethical principal in the context of psychiatric research as well as future clinical genetic testing is the respect for a person's autonomy to decide whether to undergo genetic testing, and whom to grant access to genetic data. However, experience within the psychiatric genetic research setting has indicated controversies surrounding attitudes toward this ethical principal. This study aimed to explore attitudes concerning the right of individuals to self‐determine testing and disclosure of results, and to determine whether these attitudes are context‐dependent, that is, not directly related to the test result but rather to specific circumstances. N = 160 individuals with major depression or bipolar disorder and n = 29 relatives of individuals with either illness completed an online‐questionnaire assessing attitudes toward genetic testing, genetic research, disclosure of results, incidental findings, and access to psychiatric genetic test results. Generally, the right of the person's autonomy was considered very important, but attitudes varied. For example, half of those who considered that children should have the right to refuse psychiatric genetic testing even against their parents' will, also state that they should be tested upon their parents' wishes. Also, the majority of respondents considered the physician entitled to disregard their stated wishes concerning the disclosure of incidental findings in case of good treatment options. Thus, researchers and clinicians must be aware that attitudes toward psychiatric genetic testing are often mutable and should discuss these prior to testing.     

Research participants in NGS studies want to know about incidental findings

Following the implementation of high-throughput sequencing legal and ethical issues are discussed intensively. The management of incidental findings (IFs) in a research setting have been investigated but there is a lack of literature concerning research participant''s perspective. The aim of this study was to investigate whether research participants want disclosure of IFs and what kind of IFs they want to know about. One hundred and twenty-seven research participants in a study of gastrointestinal polyps were informed about whole-exome sequencing and the risk of IFs. They were asked to decide whether they (A) wanted disclosure of IFs no matter whether the variants were associated with a non-treatable or non-preventable condition, (B) wanted disclosure of variants associated with treatable or preventable conditions or (C) wanted no disclosure at all. Participants who wanted disclosure of all the IFs (A) accounted for the majority (n=78), 45 of the participants only wanted disclosure of variants, which could lead to surveillance or treatment (B) and 4 participants did not want IFs to be disclosed at all (C). The study showed that almost all research participants wanted disclosure of at least some types of IFs.     

To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts

Any test that produces visual images or digital or genetic sequences will tend to produce incidental findings because more will be visible than what was originally sought. We conducted a systematic review of the ethical reasons presented in the literature for and against the disclosure of incidental findings arising in clinical and research genetics contexts. A search of electronic databases resulted in 13 articles included for systematic review. Articles presented reasons for and against disclosure, and reasons for proceeding with caution when making decisions about disclosure. One major recommendation of the reviewed articles is in favor of qualified disclosure: incidental findings with confirmed clinical utility where there is the possibility of treatment or prevention should be disclosed, with exceptions. A second type of recommendation is that disclosure should proceed with caution, especially in the context of new genetic technologies and genetic testing involving minors. It is also recommended that the number of possible incidental findings be limited even before genetic testing is carried out. Such a policy, which we advocate, would show preference for non-disclosure.     

Availability of treatment drives decisions of genetic health professionals about disclosure of incidental findings

Contrasting opinions exist regarding the disclosure of incidental findings detected through clinical genomic testing. This study used a discrete choice experiment to investigate genetic health professionals'' preferences for the disclosure of incidental findings in an Australian paediatric setting. Four attributes of conditions relating to incidental findings were investigated: availability of prevention and treatment, chance of symptoms ever developing, age of onset and severity. Questionnaires from 59 Australian genetic health professionals were analysed. Results show that when evaluating incidental findings for disclosure, these professionals value the availability of prevention and treatment for the condition above all other characteristics included in the study. The framework of this discrete choice experiment can be used to investigate the preferences of other stakeholders such as paediatricians and parents about disclosure of incidental findings. The results of this study may be considered when assessing which categories of incidental findings are most suitable for disclosure in clinical practice.     

Wearable devices as adjuncts in the treatment of anxiety‐related symptoms: A narrative review of five device modalities and implications for clinical practice

Anxiety disorders are a major public health problem, and a range of wearable technological devices for addressing the somatic symptoms of anxiety are increasingly available. This narrative review summarizes five distinct modalities underlying wearable devices and investigates clinical implications for managing clients using such devices. The literature suggests potential benefits of heart rate variability (HRV) biofeedback devices, while other modalities (aided meditation, false physiological feedback, electrodermal biofeedback, and respiration biofeedback) are less supported. High‐quality research on the efficacy of such devices is also lacking, particularly in clinical populations. Wearables could offer potential benefits, but may be contraindicated in some cases. Collaborative use of clinical evaluation tools, such as the American Psychiatric Association's application evaluation model, can aid in shared decision‐making about device use.     

Decision‐making for non‐invasive prenatal testing for Down syndrome: Hong Kong Chinese women's preferences for individual vs relational autonomy

Individual autonomy in antenatal screening is internationally recognized and supported. Policy and practice guidelines in various countries place emphasis on the woman's right to make her own decision and are related to concepts such as self‐determination, independence, and self‐sufficiency. In contrast, the dominant perspective in Chinese medical ethics suggests that the family is pivotal in making medical decisions, hence providing support for relational autonomy. This study explored Hong Kong Chinese pregnant women's preferences for individual vs relational autonomy for non‐invasive prenatal testing (NIPT) for Down syndrome. A qualitative study was carried out using semi‐structured interviews with 36 women who had undertaken NIPT in Hong Kong. The findings show that most Hong Kong Chinese women valued aspects of both relational and individual autonomy in decision‐making for NIPT. Women expected support from doctors as experts on the topic and wanted to involve their husband in decision‐making while retaining control over the outcome. Somewhat surprisingly, the findings do not provide support for the involvement of family members in decision‐making for NIPT. The adequacy of current interpretations of autonomy in prenatal testing policies as an individual approach needs discussion, where policy developers need to find a balance between individual and relational approaches.     

Genetics professionals' perspectives on reporting incidental findings from clinical genome‐wide sequencing

Whole exome or whole genome analysis using massively parallel sequencing technologies will undoubtedly solve diagnostic dilemmas; however, incidental findings (IF) that may have medical and social implications will also be discovered. While there is consensus in the literature that analytically valid and medically actionable IF should be returned to patients if requested, there is debate regarding the return of other IF. There are currently no guidelines established for managing IF in the clinical context. We therefore distributed an online questionnaire to 496 geneticists and genetic counselors in Canada to explore this unresolved issue, and 210 professionals participated (response rate = 42%). The proportion of respondents who indicated that they would return IF to patients depended on the nature of the finding, ranging from 95% for information pertaining to a serious and treatable condition to 12% for information with only social implications (e.g., non‐paternity). There was a lack of consensus around the disclosure of certain IF such as genetic carrier status, especially for pediatric patients. The most important considerations identified as impacting IF disclosure included condition‐specific factors such as treatment availability, test accuracy, and evidence indicating pathogenicity. This is the first study to document the views of geneticists and genetic counselors in Canada towards the disclosure of IF, and represents a step towards evidence‐based guidelines for clinical genome‐wide sequencing investigations. © 2013 Wiley Periodicals, Inc.     

The duty to warn at‐risk relatives—The experience of genetic counselors and medical geneticists

Studies published over 15 years ago surveyed genetic counselors (GC) and medical geneticists (MG) to examine their clinical experiences with the conflict of “duty to warn” versus patient confidentiality. Federal and state laws pertaining to medical professionals' duty to warn have since been implemented following the publications of these studies. Using a merged version of surveys employed in the prior studies, this study seeks to understand clinicians' current decision‐making process when faced with patient refusal to inform at‐risk relatives, as well as their familiarity with and opinions of laws and guidelines covering this issue. Consistent with the previous studies, the majority of MG and almost half of GC experience patient refusal. Significantly, fewer MG and GC believe they had a duty to warn their patients' relatives of genetic risk. Only 8% of participants believe current guidelines effectively address the issue of duty to warn. Participant awareness of federal or state laws regulating the disclosure of genetic information remains low. The conflict of duty to warn remains a shared experience among genetics professionals, and resources are needed to facilitate informed decision‐making. Participants' opinions of current policies and clinical decisions may guide professional actions regarding duty to warn.     

Next generation sequencing: considering the ethics

This review article discusses some of the ethical challenges posed by next generation sequencing (NGS), both in the clinical and research setting. Concerns such as how to deal with unexpected results apply equally to conventional techniques. However, these incidental findings are far more likely with the use of NGS and whole genome sequencing. Whilst the lines of responsibility are better defined in the clinical environment, disclosure of such findings in the research setting is less clear. Recruitment of volunteers for public biobank research, in particular, also raises questions regarding consent and confidentiality.     

Managing the need to tell: Triggers and strategic disclosure of thalassemia major in Singapore

This study explored patients' experiences and perceptions of living with thalassemia (an inherited hematologic disorder), perceptions of social stigma, and impact on disclosure decision‐making. Semistructured, in‐person interviews were conducted in Singapore with 30 individuals: 16 thalassemia major patients and 14 parents of children with thalassemia. Findings were indicative of felt or enacted stigma that may have influenced disclosure decisions. Although affected individuals commonly disclosed their thalassemia diagnosis to family members, they either downplayed the condition with or avoided disclosure to unrelated individuals. Disclosure outside the family occurred only in response to triggers, such as questions about absences due to medical care. Health professionals should provide anticipatory guidance about disclosure strategies when managing individuals with thalassemia.     

Citizens' perspectives on personalized medicine: a qualitative public deliberation study

Our objective was to explore citizens'' informed and reasoned values and expectations of personalized medicine, a timely yet novel genomics policy issue. A qualitative, public deliberation study was undertaken using a citizens'' reference panel on health technologies, established to provide input to the health technology assessment process in Ontario, Canada. The citizens'' panel consisted of five women and nine men, aged 18–71 years, with one member selected from each health authority region. There were shared expectations among the citizens'' panel members for the potential of personalized medicine technologies to improve care, provided they are deemed clinically valid and effective. These expectations were tempered by concerns about value for money and the possibility that access to treatment may be limited by personalized medicine tests used to stratify patients. Although they questioned the presumed technological imperative presented by personalized medicine technologies, they called for increased efforts to prepare the health-care system to effectively integrate these technologies. This study represents an early but important effort to explore public values toward personalized medicine. This study also provides evidence of the public''s ability to form coherent judgments about a new policy issue. Concerned that personalized tests might be used to ration care, they suggested that treatment should be made available if patients wanted it, irrespective of tests that indicate little benefit. This issue raises clinical and policy challenges that may undermine the value of personalized medicine. Further efforts to deliberate with the public are warranted to inform effective, efficient and equitable translation of personalized medicine.     

Disclosing incidental findings in genetics contexts: A review of the empirical ethical research

The disclosure of incidental findings, also called unsolicited findings, unexpected results, and secondary variants, is increasingly recognised as an issue in clinical and research genetics contexts. The rise of next generation sequencing methods has only intensified the issue, increasing the likelihood of incidental findings appearing. This review focuses on empirical research on the ethical issues involved. Electronic databases were searched for articles covering quantitative and qualitative research on the ethical issues involved in the disclosure of incidental findings in clinical and research genetics contexts. 16 articles were ultimately accepted for review. Data was extracted and synthesised on the factors that should be taken into account during the decision-making process surrounding the disclosure of an incidental finding in a genetics context. These factors include the possibility of disclosure, various practical and technical factors, and various ethical factors. We suggest the development of a decision-making tree, involving an exploration of the practical and ethical concerns raised by the studies. This is in our view the best way of handling the wide variety of both possible incidental findings and parties interested in the disclosure of incidental findings.     

Developing CollaboRATE: A fast and frugal patient-reported measure of shared decision making in clinical encounters

Objective

Measuring the process of shared decision making is a challenge, which constitutes a barrier to research and implementation. The aim of the study was to report the development of CollaboRATE, brief patient-reported measure of shared decision making.

Methods

We used the following stages: (1) item formulation; (2) cognitive interviews; (3) item refinement; and (4) pilot testing of final items. Participants were over 18 years old, recruited from the public areas of the Dartmouth-Hitchcock Medical Center.

Results

The key finding of this study is that developing a brief patient-reported measure of shared decision making requires a move away from terms such as ‘decisions’, ‘options’ and ‘preferences’. Although technically correct, these terms act as barriers. They are often unfamiliar, and they also implicitly assume that patients are willing to take active roles in decision making; whereas patients are often unaware that decisions are required, or have taken place, never mind feel that they could or should have participated in them.

Conclusion

These methods have allowed us to develop a brief, patient-reported measure of shared decision making that is highly accessible to intended users.

Practice implications

The potential strength of the CollaboRATE will be the ability for completion in less than 30 s, and across a range of routine settings.     

Attitudes of nearly 7000 health professionals,genomic researchers and publics toward the return of incidental results from sequencing research

Genome-wide sequencing in a research setting has the potential to reveal health-related information of personal or clinical utility for the study participant. There is increasing pressure to return research findings to participants that may not be related to the project aims, particularly when these could be used to prevent disease. Such secondary, unsolicited or ''incidental findings'' (IFs) may be discovered unintentionally when interpreting sequence data, or as the result of a deliberate opportunistic screen. This cross-sectional, web-based survey investigated attitudes of 6944 individuals from 75 countries towards returning IFs from genome research. Participants included four relevant stakeholder groups: 4961 members of the public, 533 genetic health professionals, 843 non-genetic health professionals and 607 genomic researchers who were invited via traditional media, social media and professional e-mail list-serve. Treatability and perceived utility of incidental results were deemed important with 98% of stakeholders personally interested in learning about preventable life-threatening conditions. Although there was a generic interest in receiving genomic information, stakeholders did not expect researchers to opportunistically screen for IFs in a research setting. On many items, genetic health professionals had significantly more conservative views compared with other stakeholders. This finding demonstrates a disconnect between the views of those handling the findings of research and those participating in research. Exploring, evaluating and ultimately addressing this disconnect should form a priority for researchers and clinicians alike. This social sciences study offers the largest dataset, published to date, of attitudes towards issues surrounding the return of IFs from sequencing research.     

Australian public perspectives on genomic data storage and sharing: Benefits,concerns and access preferences

Diagnostic genomic sequencing generates unprecedented amounts of data. In addition to its primary use, this data could be used for a wide range of secondary purposes, including research and informing future healthcare for the data donor. These opportunities may require data to be shared with third parties. Although effective data sharing relies on public support, there are barriers which may prevent people from choosing to donate their genomic data and surprisingly few studies explore these barriers in depth.To address this need, this study aimed to qualitatively explore the Australian public's views and preferences for storing and sharing genomic data. Online focus groups were recorded, transcribed, and analysed using inductive content analysis.A total of 7 focus groups were conducted with 39 members of the Australian public ranging from 18 to 67 years of age. Participants were mostly supportive of genomic data being stored and shared for secondary purposes, recognising the potential benefits for individual health and wider medical research. However, some concerns were identified. Participants felt genomic data was particularly sensitive information, and raised the potential for discrimination, stigma, and other malicious uses of such data. Concerns for privacy and security of the data were also prevalent.Trustworthiness of data users was important when considering who genomic data should be shared with. Although participants were supportive of data being freely available to health professionals and researchers, they were opposed to insurance companies and employers accessing the data. There was greater controversy around sharing data with law enforcement and pharmaceutical companies. Participants recognised both benefits and harms to sharing with law enforcement. They were also cognizant of the dual purpose of pharmaceutical companies as both research and profit-driven organisations. Finally, participants expressed varying perspectives about sharing genomic data with family members, yet most agreed that explicit consent from the data donor should be required to share their information with relatives.This study highlighted several of the Australian public's perceived barriers and motivators for the storage and sharing of genomic data. Participants recognised both the benefits of collecting, storing and sharing such data widely but also the potential for harm from data misuse. While public acceptance of such endeavours is required to maximise the volume of data made available, the concerns around data access and security need to be addressed before this can occur. These findings also highlight the nuance and ethical complexity of decisions about who we should allow to access donated genomic data. These perspectives will be essential in helping to shape the way large-scale genomic data storage and sharing is developed and implemented in Australia, and internationally.     

Treatment‐focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice

Lobb EA, Barlow‐Stewart K, Suthers G, Hallowell N. Treatment‐focused DNA testing for newly diagnosed breast cancer patients: some implications for clinical practice There is accumulating evidence that women with breast cancer due to a familial BRCA1 or BRCA2 mutation benefit from specific surgical and chemotherapeutic treatment strategies. However, the rapid identification of such patients during the acute phase of treatment raises a number of issues. This study investigated Australian opinion leaders' views on the issues arising from such ‘treatment‐focused’ genetic testing. Semi‐structured interviews with 34 opinion leaders working in cancer genetics were undertaken. Interviewees acknowledged the introduction of treatment‐focused DNA testing has the potential to positively transform the management of breast cancer patients, but were concerned that certain ethical and logistical issues have yet to be addressed. These include decision‐making and consent, the familial nature of genetic information, and the management of genetics services within familial cancer clinics in the public hospital system in Australia. Service providers will need to have policies and strategies for managing the increased demand. It will also be necessary to include genetic counseling services within familial cancer clinics in the care pathway for newly diagnosed patients prior to any DNA testing to determine adjuvant treatment; such services may be more cost‐effective than expecting surgeons and medical oncologists to fulfill this role.     

Stakeholders in psychiatry and their attitudes toward receiving pertinent and incident findings in genomic research

Increasingly more psychiatric research studies use whole genome sequencing or whole exome sequencing. Consequently, researchers face difficult questions, such as which genomic findings to return to research participants and how. This study aims to gain more knowledge on the attitudes among potential research participants and health professionals toward receiving pertinent and incidental findings. A cross‐sectional online survey was developed to investigate the attitudes among research participants toward receiving genomic findings. A total of 2,637 stakeholders responded: 241 persons with mental disorders, 671 relatives, 1,623 blood donors, 74 psychiatrists, and 28 clinical geneticists. Stakeholders wanted both pertinent findings (95%) and incidental findings (91%) to be made available for research participants. The majority (77%) stated that researchers should not actively search for incidental findings. Persons with mental disorders and relatives were generally more positive about receiving any kind of findings than clinical geneticists and psychiatrists. Compared with blood donors, persons with mental disorders reported to be more positive about receiving raw genomic data and information that is not of serious health importance. Psychiatrists and clinical geneticists were less positive about receiving genomic findings compared with blood donors. The attitudes toward receiving findings were very positive. Stakeholders were willing to refrain from receiving incidental information if it could compromise the research. Our results suggest that research participants consider themselves as altruistic participants. This study offers valuable insight, which may inform future programs aiming to develop new strategies to target issues relating to the return of findings in genomic research.