Sandi Dheensa

Defining and managing incidental findings in genetic and genomic practice

The rapidly declining costs and increasing speeds of whole-genome analysis mean that genetic testing is undergoing a shift from targeted approaches to broader ones that look at the entire genome. As whole-genome technologies gain widespread use, questions about the management of so-called incidental findings—those unrelated to the question being asked—need urgent consideration. In this review, we bring together current understanding and arguments about (1) appropriate terminology, (2) the determination of clinical utility and when to disclose incidental findings, (3) the differences in management and disclosure in clinical, research and commercial contexts and (4) ethical and practical issues about familial implications and recontacting those tested. We recommend that greater international consensus is developed around the disclosure and management of incidental findings, with particular attention to when, and how, less clear-cut results should be communicated. We suggest that there is no single term that captures all the issues around these kinds of findings and that different terms may, therefore, need to be used in different settings. We also encourage the use of clear consent processes, but suggest that the absence of consent should not always preclude disclosure. Finally, we recommend further research to identify ways to implement the use of a genome output as a resource, accessible over time, to facilitate appropriate disclosure and recontact when the significance of a previously unclear incidental finding is clarified.

Men's experiences of antenatal screening: A metasynthesis of the qualitative research

OBJECTIVES First to develop a consensus on what is known about mens experiences and involvement in antenatal screening, second to understand whether screening is an appropriate way to engage uninvolved men in pregnancy and third to identify areas requiring further research. DESIGN A systematic review was conducted to extract relevant qualitative primary research studies, which were subsequently synthesised. DATA SOURCES International qualitative research papers, in English or with English translations, were identified using twenty-three electronic databases, such as CINAHL, MEDLINE, EMBASE, PsycInfo, ASSIA and British Nursing Index. Articles that explored mens views and opinions of antenatal screening and prenatal diagnosis were included. REVIEW METHODS Eighteen relevant research studies that met the inclusion criteria were identified. Each one was appraised as suitable for inclusion using a published appraisal tool. RESULTS Three themes were constructed, which were (1) mens emotional conflicts, (2) mens focus on information and (3) mens influence on decision-making. Men felt a responsibility towards their unborn child to be involved in screening. Despite this, their input was often limited to supporting their partners, and there was no clearly defined, additional role for them as expectant fathers. Thus screening is not likely to be sufficient as an opportunity to encourage men who are uninvolved in pregnancy to become more involved. Nonetheless, engaging men who were involved in the pregnancy and who attended screening appointments was beneficial in encouraging the responsibility they felt towards their unborn child, and in allowing them to support their partners. CONCLUSIONS Healthcare professionals need to engage those men who show willingness to be involved. Nevertheless trying to engage reluctant men in screening, where there is no clearly defined role for them might create further distance between them and the pregnancy. Alternative ways to engage such men in pregnancy are thus required.

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

Purpose:The 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.Methods:Our 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.Results:Health-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.Conclusion:We 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.Genet Med 18 4, 290–301.

‘Is this knowledge mine and nobody else's? I don't feel that.’ Patient views about consent, confidentiality and information-sharing in genetic medicine

In genetic medicine, a patients diagnosis can mean their family members are also at risk, raising a question about how consent and confidentiality should function in clinical genetics. This question is particularly pressing when it is unclear whether a patient has shared information. Conventionally, healthcare professionals view confidentiality at an individual level and ‘disclosure without consent’ as the exception, not the rule. The relational joint account model, by contrast, conceptualises genetic information as confidential at the familial level and encourages professionals to take disclosure as the default position. In this study, we interviewed 33 patients about consent and confidentiality and analysed data thematically. Our first theme showed that although participants thought of certain aspects of genetic conditions—for example, the way they affect day-to-day health—as somewhat personal, they perceived genetic information—for example, the mutation in isolation—as familial. Most thought these elements were separable and thought family members had a right to know the latter, identifying a broad range of harms that would justify disclosure. Our second theme illustrated that participants nonetheless had some concerns about what, if any, implications there would be of professionals treating such information as familial and they emphasised the importance of being informed about the way their information would be shared. Based on these results, we recommend that professionals take disclosure as the default position, but make clear that they will treat genetic information as familial during initial consultations and address any concerns therein.

Recontact in clinical practice: a survey of clinical genetics services in the United Kingdom.

Purpose:To ascertain whether and how recontacting occurs in the United Kingdom.Method:A Web-based survey was administered online between October 2014 and July 2015. A link to the survey was circulated via an e-mail invitation to the clinical leads of the United Kingdom’s 23 clinical genetics services, with follow-up with senior clinical genetics staff.Results:The majority of UK services reported that they recontact patients and their family members. However, recontacting generally occurs in an ad hoc fashion when an unplanned event causes clinicians to review a file (a “trigger”). There are no standardized recontacting practices in the United Kingdom. More than half of the services were unsure whether formalized recontacting systems should be implemented. Some suggested greater patient involvement in the process of recontacting.Conclusion:This research suggests that a thorough evaluation of the efficacy and sustainability of potential recontacting systems within the National Health Service would be necessary before deciding whether and how to implement such a service or to create guidelines on best-practice models.Genet Med 18 9, 876–881.

Healthcare professionals’ and patients’ perspectives on consent to clinical genetic testing: moving towards a more relational approach

BackgroundThis paper proposes a refocusing of consent for clinical genetic testing, moving away from an emphasis on autonomy and information provision, towards an emphasis on the virtues of healthcare professionals seeking consent, and the relationships they construct with their patients.MethodsWe draw on focus groups with UK healthcare professionals working in the field of clinical genetics, as well as in-depth interviews with patients who have sought genetic testing in the UK’s National Health Service (data collected 2013–2015). We explore two aspects of consent: first, how healthcare professionals consider the act of ‘consenting’ patients; and second how these professional accounts, along with the accounts of patients, deepen our understanding of the consent process.ResultsOur findings suggest that while healthcare professionals working in genetic medicine put much effort into ensuring patients’ understanding about their impending genetic test, they acknowledge, and we show, that patients can still leave genetic consultations relatively uninformed. Moreover, we show how placing emphasis on the informational aspect of genetic testing is not always reflective of, or valuable to, patients’ decision-making. Rather, decision-making is socially contextualised – also based on factors outside of information provision.ConclusionsA more collaborative on-going consent process, grounded in virtue ethics and values of honesty, openness and trustworthiness, is proposed.

Recontacting in clinical genetics and genomic medicine? We need to talk about it

THE PROBLEM An editorial in the AJMG,1 which accompanied the first systematic review conducted on the topic,2 suggested that advances in nextgeneration sequencing technologies and the volume of genomic information they deliver are leading clinicians to consider recontacting former patients. Examples might be: (a) to discuss whether more sensitive testing could now provide a diagnosis or health prediction, which had not previously been possible; (b) to review the evidence for particular genetic findings playing a part in the patient’s disease; or (c) to revise the interpretation of a genetic variant previously identified. As the Otten et al.2 systematic review shows, there is a perceived need for guidance in this area. However, it is not clear whether a standard protocol or consensus guidelines are necessary, or indeed whether a duty to recontact exists at all.

What results to disclose, when, and who decides? Healthcare professionals' views on prenatal chromosomal microarray analysis

This study explored the views of healthcare professionals (HCPs) in the UK about what information should be disclosed, when; and whether women/parents should be given a choice as to what they wish to know.

Genetic testing of children for adult-onset conditions: opinions of the British adult population and implications for clinical practice.

This study set out to explore the attitudes of a representative sample of the British public towards genetic testing in children to predict disease in the future. We sought opinions about genetic testing for adult-onset conditions for which no prevention/treatment is available during childhood, and about genetic ‘carrier’ status to assess future reproductive risks. The study also examined participants’ level of agreement with the reasons professional organisations give in favour of deferring such testing. Participants (n=2998) completed a specially designed questionnaire, distributed by email. Nearly half of the sample (47%) agreed that parents should be able to test their child for adult-onset conditions, even if there is no treatment or prevention at time of testing. This runs contrary to professional guidance about genetic testing in children. Testing for carrier status was supported by a larger proportion (60%). A child’s future ability to decide for her/himself if and when to be tested was the least supported argument in favour of deferring testing.

Recontacting in clinical practice: the views and expectations of patients in the United Kingdom

This paper explores the views and expectations of patients concerning recontacting in clinical practice. It is based on 41 semi-structured interviews conducted in the United Kingdom. The sample comprised patients or parents of patients: without a diagnosis; recently offered a test for a condition or carrier risk; with a rare condition; with a variant of unknown significance – some of whom had been recontacted. Participants were recruited both via the National Health Service (NHS) and through online, condition-specific support groups. Most respondents viewed recontacting as desirable, however there were different opinions and expectations about what type of new information should trigger recontacting. An awareness of the potential psychological impact of receiving new information led some to suggest that recontacting should be planned, and tailored to the nature of the new information and the specific situation of patients and families. The lack of clarity about lines of responsibility for recontacting and perceptions of resource constraints in the NHS tended to mitigate respondents’ favourable positions towards recontacting and their preferences. Some respondents argued that recontacting could have a preventative value and reduce the cost of healthcare. Others challenged the idea that resources should be used to implement formalised recontacting systems – via arguments that there are ‘more pressing’ public health priorities, and for the need for healthcare services to offer care to new patients.