Health-care professionals’ responsibility to patients’ relatives in genetic medicine: a systematic review and synthesis of empirical research

PurposeThe extent of the responsibility of health-care professionals (HCPs) to ensure that patients’ relatives are told of their risk is unclear. Current international guidelines take confidentiality to the individual patient as the default position, but some suggest that disclosure could be default and genetic information could be conceptualized as familial.MethodsOur systematic review and synthesis of 17 studies explored the attitudes of HCPs, patients, and the public regarding the extent of HCPs’ responsibility to relatives with respect to disclosure.ResultsHealth-care professionals generally felt a responsibility to patients’ relatives but perceived a variety of reasons why it would be difficult to act on this responsibility. Public/patient views were more wide-ranging. Participants identified several competing and overlapping arguments for and against HCP disclosure: guidelines do not permit/mandate it, privacy, medical benefit, impact on family dynamics, quality of communication, and respecting autonomy.ConclusionWe argue that HCPs can sometimes share genetic information without breaching confidentiality and that they could factor into their considerations the potential harm to family dynamics of nondisclosure. However, we need more nuanced research about their responsibilities to relatives, particularly as genomic tests are used more frequently in clinical practice.     

Developing a conceptual,reproducible, rubric-based approach to consent and result disclosure for genetic testing by clinicians with minimal genetics background

PurposeIn response to genetic testing being widely ordered by nongenetics clinicians, the Consent and Disclosure Recommendations (CADRe) Workgroup of the Clinical Genome Resource (ClinGen; clinicalgenome.org) developed guidance to facilitate communication about genetic testing and efficiently improve the patient experience. Considering ethical, legal, and social implications, and medical factors, CADRe developed and pilot tested two rubrics addressing consent for genetic testing and results disclosure. The CADRe rubrics allow for adjusting the communication approach based on circumstances specific to patients and ordering clinicians.MethodsWe present results of a formative survey of 66 genetics clinicians to assess the consent rubric for nine genes (MLH1, CDH1, TP53, GJB2, OTC; DMD, HTT, and CYP2C9/VKORC1). We also conducted interviews and focus groups with family and patient stakeholders (N = 18), nongenetics specialists (N = 27), and genetics clinicians (N = 32) on both rubrics.ResultsFormative evaluation of the CADRe rubrics suggests key factors on which to make decisions about consent and disclosure discussions for a “typical” patient.ConclusionWe propose that the CADRe rubrics include the primary issues necessary to guide communication recommendations, and are ready for pilot testing by nongenetics clinicians. Consultation with genetics clinicians can be targeted toward more complex or intensive consent and disclosure counseling.     

Disclosure of genetic risk in the family: A survey of the Flemish general population

ObjectivesResults from genomic sequencing often have implications not just for patients but also for their relatives. To date, there are no studies in Belgium exploring whether potential relatives would want to be informed of a genetic risk in the family and their preferences on different approaches to disclosure.MethodsWe surveyed the attitudes of the Flemish general population (n = 407) towards receiving genetic information from their family members, including attitudes towards breaches in confidentiality, preferences for who communicates genetic risk and how the information is communicated, and policy approaches to nondisclosure.ResultsMost participants wanted to be informed of their genetic risk and receive genetic testing to confirm their diagnosis. Most preferred to be informed of genetic risk by a close family member, but that when given the choice between a distant family member and a clinician, most participants preferred to be contacted by a clinician.ConclusionIn Belgium there is currently no clear legal pathway for clinicians to directly initiate contact with at-risk relatives, but the responses from members of the Flemish population analyzed in this study indicate that this approach to disclosure of genetic risk deserves further consideration. Our findings indicate that the general population would support legislation allowing clinicians to inform relatives even in cases where the patient did not want to inform them. As this is not currently allowed in Belgium, policy alternatives should be considered.     

Informed consent for return of incidental findings in genomic research

PurposeResearchers face the dilemma of how to obtain consent for return of incidental findings from genomic research. We surveyed and interviewed investigators and study participants, with the goal of providing suggestions for how to shape the consent process.MethodsWe performed an online survey of 254 US genetic researchers identified through the NIH RePORTER database, abstracts from the 2011 American Society of Human Genetics meeting, and qualitative semi-structured interviews with 28 genomic researchers and 20 research participants.ResultsMost researchers and participants endorsed disclosure of a wide range of information about return of incidental findings, including risks, benefits, impact on family members, data security, and procedures, for return of results in the event of death or incapacity and for recontact. However, most researchers were willing to devote 30 min or less to this process and expressed concerns that disclosed information would overwhelm participants, a concern shared by many participants themselves.ConclusionThere is a disjunction between the views of investigators and participants about the amount of information that should be disclosed and the practical realities of the research setting, including the time available for consent discussions. This strongly suggests the need for innovative approaches to the informed consent process.     

The challenges of facilitating primary healthcare discussions on traditional,complementary and alternative medicine for childhood eczema: Piloting a computerized template

ObjectiveHealthcare practitioners (HCPs) experience barriers to changing routine consultation practice. Communication and recording of traditional, complementary and alternative medicines (TCAM) is inadequate. This pilot study explored the challenges of implementing a computerized template in primary care to facilitate communication on TCAM for paediatric eczema.MethodsA computerized template to record TCAM use, with links to evidence-based TCAM databases, was designed, based on qualitative research with patients and HCPs. Four London general practices implemented the template integrated with usual practice. Twelve focus groups during the 6 month study period explored HCPs’ knowledge, communication and information sources regarding TCAM and perceived barriers to template implementation.ResultsHCPs were initially enthusiastic about discussing TCAM, for improving communication and understanding patient's choices, but the template was used in under a third of consultations. HCPs were surprised at low TCAM use (10%) and lack of correlation with eczema or ethnicity. Reported barriers were time and remembering, due to busy, target-driven practice.ConclusionHCPs recognize the importance of discussing TCAM use for childhood eczema, and potential benefits for HCP–patient communication.Practice implicationsFuture tools to facilitate TCAM discussion should prioritise use of existing IT systems and address barriers to use, especially lack of time.     

A review of normative documents on preimplantation genetic testing: Recommendations for PGT-P

PurposeRecently, preimplantation genetic testing (PGT) for polygenic conditions (PGT-P) has been introduced commercially. In view of the lack of specific guidance on this development, we analyzed normative documents on PGT for monogenic conditions (PGT-M) to understand what we can learn from these documents for recommendations for PGT-P.MethodsWe conducted a systematic review of normative guidelines and recommendations on PGT-M. The aim was to understand what the current consensus and disagreements are on ethical acceptability of PGT-M and how this compares with PGT-P.ResultsWe analyzed 38 documents by advisory committees at the national, European, and global level. In total, 2 themes were identified, which included the following: (1) what PGT is considered appropriate for and (2) who can make decisions regarding the use of PGT. Many aspects of PGT-M documents apply to PGT-P as well. Additional factors such as the fact that PGT-P screens for risk indications of multiple polygenic conditions increase ethical difficulties regarding severity, risk, autonomy, and informed decision-making.ConclusionOn the basis of PGT-M normative documents, we conclude that ethical acceptability for PGT-P is limited. Our findings present various factors that have to be considered for the development of guidelines and the appropriateness of PGT.     

Attitudinal concordance toward uptake and disclosure of genetic testing for cancer susceptibility in patient–family member dyads

Decisions for cancer susceptibility genetic testing (CSGT) uptake and dissemination of results occur within the family context. A national survey was performed with 990 patient–family member dyads (participation rate:76.2%), with paired questionnaires examining attitudes toward CSGT uptake and disclosure of results in response to a hypothetical scenario in which a reliable CSGT was available for the specific cancer a patient was being treated. While most patients and family members responded they would uptake or recommend CSGT if available, concordance between the dyads was poor for both patient's testing (agreement rate 77.5%, weighted κ = 0.09) and first‐degree relatives' testing(agreement rate 78.0%, weighted κ = 0.09). Most patients (93.2%) and family members (92.9%) indicated that patients should disclose positive CSGT results to family members, with dyadic agreement of 89.1% (κ = 0.15). However, there were substantial disagreement regarding when disclosure should take place, who should make the disclosure (the patient or the health care professionals), and to whom the results should be disclosed. Patients and family members may hold different attitudes toward CSGT uptake of and disclosure of results within the family. Our findings reinforce the need for a family system approach to incorporate perspectives of patients as well as their family members.     

Genomic tools for health: Secondary findings as findings to be shared

PurposeWhether and how to disclose secondary finding (SF) information to children is ethically debated. Some argue that genetic testing of minors should be limited to preserve the child’s future autonomy. Others suggest that disclosure of SFs can occur if it is in the best interests of the child. However, the ways that parents conceptualize and weigh their child’s future autonomy against the interests of their child and other family members are unknown.MethodsTo explore how parents understand SF disclosure in the context of their child and other family members’ lives, we conducted semistructured interviews with 30 families (40 parents in total). All parents had children who were enrolled in a genetic sequencing protocol that returned results by default.ResultsWe found that parents did not routinely conceptualize SFs as distinctive health information. Rather parents saw this information as part of their child’s overall health. To make decisions about disclosure, parents weighed their child’s ability to understand the SF information and their other family member’s need to know.ConclusionBecause most families desired SF information, we argue that disclosure of SF be reconceptualized to reflect the lived experiences of those who may receive this information.     

A 'joint venture' model of recontacting in clinical genomics: challenges for responsible implementation

Advances in genomics often lead healthcare professionals (HCPs) to learn new information, e.g., about reinterpreted variants that could have clinical significance for patients seen previously. A question arises of whether HCPs should recontact these former patients. We present some findings interrogating the views of patients (or parents of patients) with a rare or undiagnosed condition about how such recontacting might be organised ethically and practically. Forty-one interviews were analysed thematically. Participants suggested a 'joint venture' model in which efforts to recontact are shared with HCPs. Some proposed an ICT-approach involving an electronic health record that automatically alerts them to potentially relevant updates. The need for rigorous privacy controls and transparency about who could access their data was emphasised. Importantly, these findings highlight that the lack of clarity about recontacting is a symptom of a wider problem: the lack of necessary infrastructure to pool genomic data responsibly, to aggregate it with other health data, and to enable patients/parents to receive updates. We hope that our findings will instigate a debate about the way responsibilities for recontacting under any joint venture model could be allocated, as well as the limitations and normative implications of using ICT as a solution to this intractable problem. As a first step to delineating responsibilities in the clinical setting, we suggest HCPs should routinely discuss recontacting with patients/parents, including the new information that should trigger a HCP to initiate recontact, as part of the consent process for genetic testing.     

Airmen and health-care providers’ attitudes toward the use of genomic sequencing in the US Air Force: findings from the MilSeq Project

PurposeThe use of genomic sequencing (GS) in military settings poses unique considerations, including the potential for GS to impact service members’ careers. The MilSeq Project investigated the use of GS in clinical care of active duty Airmen in the United States Air Force (USAF).MethodsWe assessed perceived risks, benefits, and attitudes toward use of GS in the USAF among patient participants (n = 93) and health-care provider participants (HCPs) (n = 12) prior to receiving or disclosing GS results.ResultsParticipants agreed that there are health benefits associated with GS (90% patients, 75% HCPs), though more HCPs (75%) than patients (40%) agreed that there are risks (p = 0.048). The majority of both groups (67% HCPs, 77% patients) agreed that they trust the USAF with genetic information, but far fewer agreed that genetic information should be used to make decisions about deployment (5% patients, 17% HCPs) or duty assignments (3% patients, 17% HCPs). Despite their hesitancy, patients were supportive of the USAF testing for nondisease traits that could impact their duty performance. Eighty-seven percent of patients did not think their GS results would influence their career.ConclusionResults suggest favorable attitudes toward the use of GS in the USAF when not used for deployment or assignment decisions.     

Diagnosis,treatment and disclosure: A qualitative exploration of participant challenges in a Monogenic Diabetes Registry

PurposeMaturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic diabetes. Despite its autosomal dominant inheritance, many MODY participants in the University of Chicago Monogenic Diabetes Registry have no family members enrolled. We aimed to gather data on the Registry participants’ experiences in (1) receipt of an accurate diagnosis, (2) decisions regarding disclosure of their MODY genetic test results with biological relatives, and (3) recommendations toward our Registry’s processes and outreach.MethodsWe conducted 20 one-on-one semistructured interviews with adult Registry participants.ResultsAll participants found navigating the health care system challenging because of the providers’ unfamiliarity with MODY and dismissal of its importance post diagnosis. All had shared their results with at least 1 relative, however many found their relatives resistant to engaging with their providers. Participants wanted to receive targeted information on their condition and connect with other participants who have faced similar diagnostic and treatment challenges.ConclusionOur results demonstrate that our probands faced resistance to reclassification of their diabetes from both health care providers and relatives. In an effort to improve cascade testing, the Registry is designing a portal to facilitate participant–research team communication and provide additional supports for participants to involve family members in testing.     

Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility

PurposeMultiplex genetic testing, including both moderate- and high-penetrance genes for cancer susceptibility, is associated with greater uncertainty than traditional testing, presenting challenges to informed consent and genetic counseling. We sought to develop a new model for informed consent and genetic counseling for four ongoing studies.MethodsDrawing from professional guidelines, literature, conceptual frameworks, and clinical experience, a multidisciplinary group developed a tiered-binned genetic counseling approach proposed to facilitate informed consent and improve outcomes of cancer susceptibility multiplex testing.ResultsIn this model, tier 1 “indispensable” information is presented to all patients. More specific tier 2 information is provided to support variable informational needs among diverse patient populations. Clinically relevant information is “binned” into groups to minimize information overload, support informed decision making, and facilitate adaptive responses to testing. Seven essential elements of informed consent are provided to address the unique limitations, risks, and uncertainties of multiplex testing.ConclusionA tiered-binned model for informed consent and genetic counseling has the potential to address the challenges of multiplex testing for cancer susceptibility and to support informed decision making and adaptive responses to testing. Future prospective studies including patient-reported outcomes are needed to inform how to best incorporate multiplex testing for cancer susceptibility into clinical practice.Genet Med 17 6, 485–492.     

Challenges of variant reinterpretation: Opinions of stakeholders and need for guidelines

PurposeThe knowledge used to classify genetic variants is continually evolving, and the classification can change on the basis of newly available data. Although up-to-date variant classification is essential for clinical management, reproductive planning, and identifying at-risk family members, there is no consistent practice across laboratories or clinicians on how or under what circumstances to perform variant reinterpretation.MethodsWe conducted exploratory focus groups (N = 142) and surveys (N = 1753) with stakeholders involved in the process of variant reinterpretation (laboratory directors, clinical geneticists, genetic counselors, nongenetic providers, and patients/parents) to assess opinions on key issues, including initiation of reinterpretation, variants to report, termination of the responsibility to reinterpret, and concerns about consent, cost, and liability.ResultsStakeholders widely agreed that there should be no fixed termination point to the responsibility to reinterpret a previously reported genetic variant. There were significant concerns about liability and lack of agreement about many logistical aspects of variant reinterpretation.ConclusionOur findings suggest a need to (1) develop consensus and (2) create transparency and awareness about the roles and responsibilities of parties involved in variant reinterpretation. These data provide a foundation for developing guidelines on variant reinterpretation that can aid in the development of a low-cost, scalable, and accessible approach.     

Deaf in one ear: Communication and social challenges of patients with single-sided deafness post-diagnosis

ObjectiveTo understand the communication and social challenges that individuals with SSD face post diagnosis.MethodsFifty-two single-sided deaf patients from all over the world participated in semi-structured interviews. Interviews were digitally recorded, transcribed verbatim, and coded using a thematic analysis approach.ResultsPatients with single sided deafness identified challenges including: increased reliance on family members, decreased sense of autonomy, communication quality changes with family members, information discrepancy across family members and various emotional responses, conflicting information from interactions with multiple medical professionals, and lack of knowledge regarding what to anticipate post diagnosis.ConclusionThis study provides insights into patients’ perspectives around single-sided deafness and its challenges, and the various health care approaches (e.g., patient- and family-centered care, third party disability, patient navigation) that could be implemented post diagnosis to decrease negative experiences and outcomes associated with SSD.Practical ImplicationsThis study has practical implications for improving our understanding of what single-sided deaf patients need and for health professionals to offer better care to current and future populations impacted by single-sided deafness.     

Genetic medicine and incidental findings: it is more complicated than deciding whether to disclose or not

PurposeThe aim of this study was to explore the clinical management of incidental findings. Advances in the speed and sensitivity of genetic technologies have not only improved the diagnostic rate but also result in an increase in unanticipated diagnoses. Recent debate on such “incidental findings” has considered whether or not to actively search for and, then, disclose incidental findings. In our experience, many incidental findings need to be investigated in family members before their clinical significance can be assessed. This adds complexity to the debate about disclosure.MethodsUsing anonymized clinical examples, we illustrate the downstream implications when a result reveals an incidental abnormality of potential clinical significance that is not related to the reasons for doing the test.ResultsOur examples illustrate that the determination of clinical significance may require participation of family members in both testing and surveillance.ConclusionThe need to investigate multiple relatives in order to decide whether or not a finding is clinically significant has implications for consent and disclosure practices. Communication with, and care for, relatives who have no reason to suspect particular diagnoses is a challenge for any health-care service. These costs also need to be taken into account as genetic testing enters mainstream medicine.     

Patient and family member perspectives on searching for cancer clinical trials: A qualitative interview study

ObjectiveClinical trials are vital in the context of ovarian cancer and may offer further treatment options during disease recurrence, yet enrollment remains low. Understanding patient and family member experiences with identifying trials can inform engagement and education efforts.MethodsInterviews were conducted with 33 patients who had experience with clinical trial conversations and 39 nominated family members. Thematic analysis examined experiences and generated findings for clinical practice.ResultsTrial conversations with providers at diagnosis were uncommon and often overwhelming. Most participants delayed engagement until later in the disease course. With hindsight, though, some wished they considered trials earlier. Difficulty identifying appropriate trials led some to defer searching to providers, but then they worried about missed opportunities. Most family members felt unqualified to search.ConclusionTrial conversations during clinical encounters should start early and include specifying search responsibilities of providers, patients, and family. Patients and family members can be engaged in searches but need guidance.Practice implicationsTrials should be discussed throughout the disease course, even if patients are not ready to participate or are not making a treatment decision. Education should focus on identifying trials that meet search criteria. Transparency regarding each individual’s role in identifying trials is critical.     

Development of a consent resource for genomic data sharing in the clinical setting

PurposeData sharing between clinicians, laboratories, and patients is essential for improvements in genomic medicine, but obtaining consent for individual-level data sharing is often hindered by a lack of time and resources. To address this issue, the Clinical Genome Resource (ClinGen) developed tools to facilitate consent, including a one-page consent form and online supplemental video with information on key topics, such as risks and benefits of data sharing.MethodsTo determine whether the consent form and video accurately conveyed key data sharing concepts, we surveyed 5,162 members of the general public. We measured comprehension at baseline, after reading the form and watching the video. Additionally, we assessed participants’ attitudes toward genomic data sharing.ResultsParticipants’ performance on comprehension questions significantly improved over baseline after reading the form and continued to improve after watching the video.ConclusionResults suggest reading the form alone provided participants with important knowledge regarding broad data sharing, and watching the video allowed for broader comprehension. These materials are now available at http://www.clinicalgenome.org/share. These resources will provide patients a straightforward way to share their genetic and health information, and improve the scientific community’s access to data generated through routine healthcare.     

Current understanding of genetics and genetic testing and information needs and preferences of adults with inherited retinal disease

Advances in sequencing technology and the movement of genetic testing into all areas of medicine will increase opportunities for molecular confirmation of a clinical diagnosis. For health-care professionals without formal genetics training, there is a need to know what patients understand about genetics and genetic testing and their information needs and preferences for the disclosure of genetic testing results. These topics were explored during face-to-face interviews with 50 adults with inherited retinal disease, selected in order to provide a diversity of opinions. Participants had variable understanding of genetics and genetic testing, including basic concepts such as inheritance patterns and the risk to dependents, and many did not understand the term ‘genetic counselling''. Most were keen for extra information on the risk to others, the process for genetic testing and how to share the information with other family members. Participants were divided as to whether genetic testing should be offered at the time of the initial diagnosis or later. Many would prefer the results to be given by face-to-face consultation, supplemented by further information in a format accessible to those with visual impairment. Health-care professionals and either leaflets or websites of trusted agencies were the preferred sources of information. Permission should be sought for disclosure of genetic information to other family members. The information needs of many patients with inherited retinal disease appear to be unmet. An understanding of their information needs and preferences is required to help health-care professionals provide optimal services that meet patient expectations.     

Oncology team members' perceptions of a virtual navigation tool for cancer patients

ObjectivesThe Internet has become an important source of health information for patients and health care providers (HCPs) alike. Whereas studies have begun to document the effects of the internet on health behaviors and outcomes, surprisingly few studies have explored HCPs’ perceptions of the internet as a key resource accessed by patients. However, as HCPs are seen as pivotal in guiding patients toward these resources, it is timely to study their perceptions. Therefore, the present inquiry explores HCPs’ views of a recently developed high quality virtual navigation tool called the Oncology Interactive Navigator? (OIN).DesignUsing a qualitative approach, in-depth interviews were conducted with 16 members of a multidisciplinary colorectal oncology team and volunteers at a large Cancer Centre in Montreal, Quebec, Canada.ResultsContent analysis revealed emerging themes centering on key benefits including: perceptions of a highly accessible, comprehensive high quality repository of cancer information; a means to further enhance HCP-patient communication and trust; and a significant catalyst to patient–family communication and support. Perceived drawbacks included patient (e.g., socio-demographic profile) and system's (e.g., professional roles and time constraints) characteristics that may limit OIN? full implementation and uptake.ConclusionsThe findings underscore the relevance of virtual navigation tools to ensure optimal person-centred care in cancer. Findings also suggest how virtual tools such as the OIN? can best be used in practice as well as they guide strategies to adopt to optimize implementation of similar innovations in health care.     

Outcomes of patient self-referral for the diagnosis of several rare inherited kidney diseases

PurposeTo evaluate self-referral from the Internet for genetic diagnosis of several rare inherited kidney diseases.MethodsRetrospective study from 1996 to 2017 analyzing data from an academic referral center specializing in autosomal dominant tubulointerstitial kidney disease (ADTKD). Individuals were referred by academic health-care providers (HCPs) nonacademic HCPs, or directly by patients/families.ResultsOver 21 years, there were 665 referrals, with 176 (27%) directly from families, 269 (40%) from academic HCPs, and 220 (33%) from nonacademic HCPs. Forty-two (24%) direct family referrals had positive genetic testing versus 73 (27%) families from academic HCPs and 55 (25%) from nonacademic HCPs (P = 0.72). Ninety-nine percent of direct family contacts were white and resided in zip code locations with a mean median income of $77,316 ± 34,014 versus US median income $49,445.ConclusionUndiagnosed families with Internet access bypassed their physicians and established direct contact with an academic center specializing in inherited kidney disease to achieve a diagnosis. Twenty-five percent of all families diagnosed with ADTKD were the result of direct family referral and would otherwise have been undiagnosed. If patients suspect a rare disorder that is undiagnosed by their physicians, actively pursuing self-diagnosis using the Internet can be successful. Centers interested in rare disorders should consider improving direct access to families.