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

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

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.     

Pitfalls in the interpretation of CFTR variants in the context of incidental findings

Whole‐exome/genome sequencing analyses lead to detect disease‐causing variants that are unrelated to the initial clinical question. Irrespective of any actionable gene list, only pathogenic variants should be considered. The pathogenicity of 55 cystic fibrosis transmembrane conductance regulator (CFTR) variants of known various impacts was assessed by a group of experts by comparing data from specialized databases CFTR‐France and CFTR2 with those of general clinical databases ClinVar and Human Gene Mutation Database (HGMD®) Professional and data aggregators VarSome and InterVar. The assessment of cystic fibrosis (CF) variants was correct with ClinVar and HGMD® Professional while less reliable with VarSome and InterVar. Conversely, the risk of overclassifying variants as CF‐causing was up to 82% with HGMD® Professional. The concordance between data aggregators was only 50%. The use of general databases and aggregators is thus associated with a substantial risk of misclassifying variants. This evaluation may be extrapolated to other disease conditions and incites to remain cautious in interpreting and disclosing incidental findings.     

A decision aid for additional findings in genomic sequencing: Development and pilot testing

ObjectiveTo describe the development of a web-based, patient-facing decision aid to support patients and research participants to make an informed, values-based decision about whether to receive additional results from genomic sequencing.MethodsWe developed the decision aid following the multi-step process described in the International Patient Decision Aids Standards. This utilized literature review, focus groups, and alpha testing with research participants undergoing clinical genomic sequencing.ResultsThe decision aid, the Optional Results Choice Aid (ORCA), includes a seven-question “values clarification exercise,” illustrative patient quotes, and summative guidance for the user. The decision aid was found to be highly readable, acceptable and relevant in alpha testing.ConclusionWe developed a decision aid to support informed, values-based decision making for patients and research participants considering whether to receive additional results from genomic sequencing. ORCA is being implemented in the NHGRI-funded Cancer Health Assessment Reaching Many (CHARM) study, where we are measuring informed values-choice congruence.Practice implicationsORCA was designed to support patients and research participants to make an informed, values-based decision about whether to receive additional results from genomic sequencing.     

Incidental findings in a series of 2500 gene panel tests for a genetic predisposition to cancer: Results and impact on patients

With next generation sequencing, physicians are faced with more complex and uncertain data, particularly incidental findings (IF). Guidelines for the return of IF have been published by learned societies. However, little is known about how patients are affected by these results in a context of oncogenetic testing. Over 4 years, 2500 patients with an indication for genetic testing underwent a gene cancer panel. If an IF was detected, patients were contacted by a physician/genetic counsellor and invited to take part in a semi-structured interview to assess their understanding of the result, the change in medical care, the psychological impact, and the transmission of results to the family. Fourteen patients (0.56%) were delivered an IF in a cancer predisposition gene (RAD51C, PMS2, SDHC, RET, BRCA2, CHEK2, CDKN2A, CDH1, SUFU). Two patients did not collect the results and another two died before the return of results. Within the 10 patients recontacted, most of them reported surprise at the delivery of IF, but not anxiety. The majority felt they had chosen to obtain the result and enough information to understand it. They all initiated the recommended follow-up and did not regret the procedure. Information regarding the IF was transmitted to their offspring but siblings or second-degree relatives were not consistently informed. No major adverse psychological events were found in our experience. IF will be inherent to the development of sequencing, even for restricted gene panels, so it is important to increase our knowledge on the impact of such results in different contexts.     

Nudging in screening: Literature review and ethical guidance

Objectives

Nudging is the purposeful alteration of choices presented to people that aims to make them choose in predicted ways. While nudging has been used to assure high uptake and good outcome of screening programs, it has been criticized for being paternalistic, undermining free choice, and shared decision making. Accordingly, the objective of this study is to explore a) nudging strategies identified in screening, b) arguments for and against nudging; and on basis of this, to c) suggest a tentative conclusion on how to handle nudging in screening.

‘Information is information’: a public perspective on incidental findings in clinical and research genome‐based testing

The potential for genomic incidental findings is increasing with the use of genome‐based testing. At the same time approaches to clinical decision making are shifting to shared decision‐making models involving both the healthcare community and the public. The public's voice has been nearly absent in discussions on managing incidental findings. We conducted nine focus groups and nine interviews (n = 63) with a broad cross‐section of lay public groups to elucidate public viewpoints on incidental findings that could occur as a result of genome‐based testing in clinical and research situations. Data were analyzed using qualitative content analysis. Participants wanted incidental findings disclosed to them whether or not these were clinical or research findings. Participants used different terms to define and describe incidental findings; they wanted to know that incidental findings are possible and be given a choice to learn about them. Personal utility was an important reason for disclosure, and participants believed that managing information is a shared responsibility between professionals and themselves. Broad public input is needed in order to understand and incorporate the public's perspective on management of incidental findings as disclosure guidelines, and policies are developed in clinical and research settings.     

Proteomics in pathology, research and practice: ethical considerations

A researcher should always seek advice from his responsible ethics committee. Usually, advisory discussions with physicians doing research are not problematic in ethical terms when they want to examine biological material obtained, especially, when the material is no longer needed, the material will be used anonymized, no individualizing genes will be examined, the aims of research are not disputed in ethical terms, research is not expected to yield results of individual relevance to the person affected, there is no indication that the person affected will object to research and the expenditure for obtaining the individual consent is excessively high.     

ORCA,a values-based decision aid for selecting additional findings from genomic sequencing in adults: Efficacy results from a randomized trial

PurposeIndividuals having genomic sequencing can choose to be notified about pathogenic variants in genes unrelated to the testing indication. A decision aid can facilitate weighing one’s values before making a choice about these additional results.MethodsWe conducted a randomized trial (N = 231) comparing informed values-choice congruence among adults at risk for a hereditary cancer syndrome who viewed either the Optional Results Choice Aid (ORCA) or web-based additional findings information alone. ORCA is values-focused with a low-literacy design.ResultsIndividuals in both arms had informed values-choice congruence (75% and 73% in the decision aid and web-based groups, respectively; odds ratio [OR] = 1.10, 95% CI = 0.58-2.08). Most participants had adequate knowledge (79% and 76% in the decision aid and web-based groups, respectively; OR = 1.20, 95% CI = 0.61-2.34), with no significant difference between groups. Most had information-seeking values (97% and 98% in the decision aid and web-based groups, respectively; OR = 0.59, 95% CI = 0.10-3.61) and chose to receive additional findings.ConclusionThe ORCA decision aid did not significantly improve informed values-choice congruence over web-based information in this cohort of adults deciding about genomic results. Both web-based approaches may be effective for adults to decide about receiving medically actionable additional results.     

An empirical examination of the management of return of individual research results and incidental findings in genomic biobanks

PurposeThe purpose of this study was to examine and document the management and return of individual research results and incidental findings to research participants among biobanks.MethodsA comprehensive Internet search was completed to identify biobanks and collect available documents about biobanks and their procedures and policies regarding the return of results. The Internet search was supplemented by an e-mail request to gather further such documents. A total of 2,366 documents were collected for analysis from a sample of 85 biobanks.ResultsThe major finding of this empirical work is that the majority of the biobanks in the sample do not address the return of individual research results and incidental findings in their publicly available documents.ConclusionThe results suggest that there is a need for more discussion and guidance about the most appropriate ways for biobanks to consider the return of individual research results and incidental findings and generate policies and procedures that address this issue.Genet Med 2012:14(4):444–450     

Sexual abuse of children: A review of the empirical findings

This paper reviews empirical findings of the past decade concerning the incidence and effects of child sexual abuse. First, incidence studies which consider intrafamilial and extrafamilial abuse victims of both sexes are reviewed. Research findings on short- and longterm consequences to female incest victims are then reported. Risk factors are identified for the child, the perpetrator, and the nonoffending caretaker. Theoretical literature is discussed to a limited extent throughout. To date, few empirical studies have utilized large sample sizes, adequate comparison groups, objective measures, and statistical data analysis. More well-designed research is needed so that fuller explanatory models of child sexual abuse can be developed. Symptomatology of the abuser, characteristics of the abused, and situational variables must be considered concurrently to strengthen prediction, develop effective prevention programs, and clarify treatment goals.     

Sugar and hyperactivity: A critical review of empirical findings

Studies examining the effects of sugar ingestion on the behavior of children, both normal and hyperactive, were reviewed. Although the results of correlational studies suggested that high levels of sugar consumption may be associated with increased rates of inappropriate behavior, the results of dietary challenge studies have been inconsistent and inconclusive. Most studies have failed to find any effects associated with sugar ingestion, and the few studies that have found effects have been as likely to find sugar improving behavior as making it worse. Design parameters unique to undertaking sugar challenge studies were identified, and suggestions for future research were offered     

Managing clinically significant findings in research: the UK10K example

Recent advances in sequencing technology allow data on the human genome to be generated more quickly and in greater detail than ever before. Such detail includes findings that may be of significance to the health of the research participant involved. Although research studies generally do not feed back information on clinically significant findings (CSFs) to participants, this stance is increasingly being questioned. There may be difficulties and risks in feeding clinically significant information back to research participants, however, the UK10K consortium sought to address these by creating a detailed management pathway. This was not intended to create any obligation upon the researchers to feed back any CSFs they discovered. Instead, it provides a mechanism to ensure that any such findings can be passed on to the participant where appropriate. This paper describes this mechanism and the specific criteria, which must be fulfilled in order for a finding and participant to qualify for feedback. This mechanism could be used by future research consortia, and may also assist in the development of sound principles for dealing with CSFs.     

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.