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In this paper, we explore key aspects of the complex ethical and legal landscape surrounding consent in the context of incorporating genomic sequencing into existing newborn bloodspot screening programs. In particular, we consider the potential impact of genomic sequencing on the health rights of the child in relation to existing consent practices in newborn screening. We begin with an introduction to newborn screening programs and their population health goals. We then discuss public health ethics as a rationale underpinning newborn screening before turning to consent. We go on to describe seven current research projects on genomic sequencing in newborn screening and then introduce the ‘right of the asymptomatic at-risk child to be found’ as a useful concept to draw on when considering consent to newborn screening. We draw on this novel right to argue for the adoption of “appropriate consent” when it comes to certain uses of genomics in newborn screening. We contend that, for ‘virtual panels’ at least, appropriate consent proportionately balances the ongoing universality of newborn screening for important health conditions with an acknowledgement of the complex outcomes that bringing a complicated diagnostic technology into the screening domain will generate.

The notion of a “serious” genetic condition is commonly used in clinical contexts, laws, and policies to define and delineate both the permissibility of and, access to, reproductive genomic technologies. Yet, the notion lacks conceptual and operational clarity, which can lead to its inconsistent appraisal and application. A common understanding of the relevant considerations of “serious” is lacking. This article addresses this conceptual gap. We begin by outlining existing distinctions around the notion of “serious” that will factor into its appraisal and need to be navigated, in the context of prenatal testing and the use of reproductive genomic technologies. These include tensions between clinical care and population health; the impact of categorizing a condition as “serious”; and the role of perception of quality of life. We then propose a set of four core dimensions and four procedural elements that can serve as a conceptual tool to prompt a mapping of the features of seriousness in any given context. Ultimately, consideration of these core dimensions and procedural elements may lead to improvements in the quality and consistency of decision-making where the seriousness of a genetic condition is a pivotal component at both a policy and practice level.

Multiple studies show that periodic reanalysis of genomic test results held by clinical laboratories delivers significant increases in overall diagnostic yield. However, while there is a widespread consensus that implementing routine reanalysis procedures is highly desirable, there is an equally widespread understanding that routine reanalysis of individual patient results is not presently feasible to perform for all patients. Instead, researchers, geneticists and ethicists are beginning to turn their attention to one part of reanalysis—reinterpretation of previously classified variants—as a means of achieving similar ends to large-scale individual reanalysis but in a more sustainable manner. This has led some to ask whether the responsible implementation of genomics in healthcare requires that diagnostic laboratories routinely reinterpret their genomic variant classifications and reissue patient reports in the case of materially relevant changes. In this paper, we set out the nature and scope of any such obligation, and analyse some of the main ethical considerations pertaining to a putative duty to reinterpret. We discern and assess three potential outcomes of reinterpretation—upgrades, downgrades and regrades—in light of ongoing duties of care, systemic error risks and diagnostic equity. We argue against the existence of any general duty to reinterpret genomic variant classifications, yet we contend that a suitably restricted duty to reinterpret ought to be recognised, and that the responsible implementation of genomics into healthcare must take this into account.

Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n= 335) and their genetic relatives (n= 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n= 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is preventionor treatmentthat can change cancer risk compared to conditions for which there is no preventionor treatment(93% [311] versus 65% [216]; p< 0.001). Similar results were obtained for relatives (91% [180] versus 61% [121]; p< 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.

Reproductive genetic carrier screening (RGCS) may be offered to all individuals and couples, regardless of family history or ethnicity. “Mackenzie’s Mission” (MM) is an Australian RGCS pilot study, evaluating the offer of couple-based screening for ~1300 genes associated with around 750 autosomal and X-linked recessive childhood-onset conditions. Each member of the couple makes an individual decision about RGCS and provides consent. We developed a decision aid (RGCS-DA) to support informed decision-making in MM, suitable for couples who were either non-pregnant or in early pregnancy. A Delphi approach invited experts to review values statements related to various concepts of RGCS. Three review rounds were completed, seeking consensus for relevance and clarity of statements, incorporating recommended modifications in subsequent iterations. The final RGCS-DA contains 14 statements that achieved Delphi consensus plus the attitude scale of the measure of informed choice. This was then evaluated in cognitive talk aloud interviews with potential users to assess face and content validity. Minimal wording changes were required at this stage. After this process, the RGCS-DA was piloted with 15 couples participating in MM who were then interviewed about their decision-making. The RGCS-DA prompted discussion within couples and facilitated in depth consideration of screening. There was reassurance when values aligned and a sense of shared decision-making within the couple. This RGCS-DA may become a very useful tool in supporting couples’ decision making and contribute to RGCS being feasible for scaled-up implementation.

Reproductive genetic carrier screening (RCS), when offered to anyone regardless of their family history or ancestry, has been subject to the critique that it is a form of eugenics. Eugenics describes a range of practices that seek to use the science of heredity to improve the genetic composition of a population group. The term is associated with a range of unethical programmes that were taken up in various countries during the 20th century. Contemporary practice in medical genetics has, understandably, distanced itself from such programmes. However, as RCS becomes more widespread, gains public funding and uses expanded gene panels, there are concerns that such programmes could be perceived as eugenic either in intent or outcome. The typical response to the eugenics critique of RCS is to emphasise the voluntary nature of both participating in screening and making subsequent reproductive choices. While safeguarding individuals’ freedom to choose in relation to screening is essential, we consider this response inadequate. By examining the specific ethical wrongs committed by eugenics in the past, we argue that to avoid the perception of RCS being a form of eugenics it is essential to attend to the broader normative context in which reproductive decisions occur. Furthermore, ethical RCS programmes must recognise and respond to their potential to shift societal norms that shape individual reproductive choices.

We evaluated the impact of personal melanoma genomic risk information on sun-related behaviors and psychological outcomes.

Knowledge of genetic mechanisms contributing to neurodevelopmental conditions is advancing. This is informing development of new drugs to treat or ameliorate these conditions, through targeting underlying genetic pathways. Drugs are tested in clinical trials, necessitating parents to engage with decisions about whether to enroll their child. In this article, we consider important ethical issues to anticipate as clinical research opportunities in genetic neurodevelopmental conditions arise. For example, genetic pathways targeted by the drugs may interact with valued character and personality traits. It is essential that recruitment and consent processes are optimized for families who will grapple with whether these novel drug treatments interact with their child's personality and authentic identity. We call for focused social science research and further normative analysis so that parents are better supported to make informed choices. Additionally, clinical research regulators should have a sound understanding of the contextual experiences regarding how this population of parents engages with decisions.

Reproductive genetic carrier screening aims to offer couples information about their chance of having children with certain autosomal recessive and X-linked genetic conditions. We developed a gene list for use in “Mackenzie’s Mission”, a research project in which 10,000 couples will undergo screening. Criteria for selecting genes were: the condition should be life-limiting or disabling, with childhood onset, such that couples would be likely to take steps to avoid having an affected child; and/or be one for which early diagnosis and intervention would substantially change outcome. Strong evidence for gene-phenotype relationship was required. Candidate genes were identified from OMIM and via review of 23 commercial and published gene lists. Genes were reviewed by 16 clinical geneticists using a standard operating procedure, in a process overseen by a multidisciplinary committee which included clinical geneticists, genetic counselors, an ethicist, a parent of a child with a genetic condition and scientists from diagnostic and research backgrounds. 1300 genes met criteria. Genes associated with non-syndromic deafness and non-syndromic differences of sex development were not included. Our experience has highlighted that gene selection for a carrier screening panel needs to be a dynamic process with ongoing review and refinement.

BackgroundLittle is known about knowledge of, and attitudes towards, genome sequencing (GS) among individuals with a personal history of cancer who decide to undergo GS. This qualitative study aimed to investigate baseline knowledge and attitudes among individuals previously diagnosed with a cancer of likely genetic origin who have consented to GS.MethodsSemistructured interviews were conducted with purposively selected participants (n=20) from the longitudinal Psychosocial Issues in Genomic Oncology study, within a month of consenting to GS and prior to receiving any results. Participants were adults with a cancer of likely genetic aetiology who are undertaking GS as part of a larger genetic study.ResultsAnalysis identified three main themes: limited understanding of genomics; multifactorial motivation; and complex decision making. While motivations such as obtaining health information about self and family appear to be the main drivers for undertaking GS, these motivations are sometimes based on limited knowledge of the accuracy and utility of GS, creating unrealistic expectations. This in turn can prolong the deliberation process and lead to ongoing decisional conflict.ConclusionUnderstanding the degree and nature of patient understanding of GS, as well as their attitudes and decision-making processes, will enable healthcare professionals to better manage patient expectations and appropriately engage and support patients to make an informed decision when pursuing GS.

Genomics is increasingly being incorporated into models of care for cancer. Understanding the ethical, legal, and social implications (ELSI) in this domain is important for successful and equitable implementation. We aimed to identify ELSI scholarship specific to cancer control and genomics. To do this, we undertook a scoping literature review and narrative synthesis, identifying 46 articles that met inclusion criteria. Eighteen ELSI themes were developed, including (1) equity of access, which included structural barriers to testing and research, access to preventive and follow-up care, and engagement with health systems; (2) family considerations, such as an ethical obligation to disseminate relevant genomic information to at-risk family members; (3) legal considerations, including privacy and confidentiality, genetic discrimination, and the prospective duty to reclassify variants; and (4) optimizing consent processes in clinical care and research. Gaps in the literature were identified with respect to equity for people living in rural or remote areas, and how to provide ethical care within culturally, linguistically, and ethnically diverse communities, including First Nations peoples. Our findings suggest a need for a multidisciplinary approach to examining ELSI in cancer genomics beyond initial test indication and within the broader context of the mainstreaming of genomics in health care.

Evidence indicates that a melanoma prevention program using personalized genomic risk provision and genetic counseling can affect prevention behaviors, including reducing sunburns in adults with no melanoma history. This analysis evaluated its longer-term cost-effectiveness from an Australian health system perspective.

Personal genomic tests (PGTs) for multiple purposes are marketed to ostensibly healthy people in Australia. These tests are generally marketed and purchased online commercially or can be ordered through a health professional. There has been minimal engagement with Australians about their interest in and experience with ordering a PGT. As part of a multistage, interdisciplinary project, an online survey (Stage 2 of the Genioz study) was available from May 2016 to May 2017. In total, 3253 respondents attempted the survey, with 2395 completed Australian responses from people with and without experience of having a PGT: 72% were female; 59% of the whole sample were undertaking/or had a university education; and, overall, age ranged from 18—over 80. A total of 571 respondents reported having had a genetic test, 373 of these classifiable as a PGT. A bivariate analysis suggests people who have undergone PGT in our sample were: women aged 25 and over; or in a high socioeconomic group, or have a personal or family diagnosis of a genetic condition (P≤ 0.03). After a multivariate analysis, socioeconomic status and a genetic condition in the family were not of significance. The most common types of PGT reported were for carrier status and ancestry. Findings suggest greater awareness of, and an increasing demand for non-health related PGT in Australia. To support both consumers and health care professionals with understanding PGT results, there is a need for appropriate support and resources.

The law often calls on the concept of public interest for assistance. Privacy law makes use of this concept in several ways, including to justify consent waivers for secondary research on health information. Because the law sees information privacy as a means for individuals to control their personal information, consent can only be set aside in special circumstances. Ballantyne and Schaefer argue that only public interest, and only a broad conception of public interest, can do the special ‘normative justificatory work’ to override consent requirements. Other, similar-sounding concepts, such as public benefit, public good and social value, also provide useful services. But none more so than public interest. In fact, they argue, public interest is the superior concept precisely because it can capture those concepts as well as a range of other interests. Our response focuses on this claim. We argue their strategy is not as promising as it might first seem. Ballantyne and Schaefer construe the important role that public interest plays in this context as their endpoint. They claim that unless the concept is open and content-rich, it will lose some of its importance. But by refusing to place limits around it, their inquiry leads us back to a catch-all concept that lacks clear focus or meaning. In reply, we argue that, for practically minded theorists, a narrow conception of public interest is more useful. Further, the narrowing of public interest in this context can be achieved by first analysing it in its legal, rather than ethical, sense.

Genome sequencing can generate findings beyond the initial test indication that may be relevant to a patient or research participant’s health. In the decade since the American College of Medical Genetics and Genomics published its recommendations for reporting these findings, consensus regarding terminology has remained elusive and a variety of terms are in use globally. We conducted a scoping review to explore terminology choice and the justifications underlying those choices. Documents were included if they contained a justification for their choice of term(s) related to findings beyond the initial genomic test indication. From 3571 unique documents, 52 were included, just over half of which pertained to the clinical context (n = 29, 56%). We identified 4 inter-related concepts used to defend or oppose terms: expectedness of the finding, effective communication, relatedness to the original test indication, and how genomic information was generated. A variety of justifications were used to oppose the term “incidental,” whereas “secondary” has broader support as a term to describe findings deliberately sought. Terminology choice would benefit from further work to include the views of patients. We contend that clear definitions will improve ethical debate and support communication about genomic findings beyond the initial test indication.

Most academic journals that publish studies involving human participants require evidence that the research has been approved by a human research ethics committee (HREC). Yet journals continue to receive submissions from authors who have failed to obtain such approval. In this paper, we provide an ethical justification of why journals should not, in general, publish articles describing research that has no ethics approval, with particular attention to the health promotion context. Using theoretical bioethical reasoning and drawing on a case study, we first rebut some potential criticisms of the need for research ethics approval. We then outline four positive claims to justify a presumption that research should, in most instances, be published only if it has been undertaken with HREC approval. We present four justifications for requiring ethics approval before publication: (1) HREC approval adds legitimacy to the research; (2) the process of obtaining HREC approval can improve the quality of an intervention being investigated; (3) obtaining HREC approval can help mitigate harm; and (4) obtaining HREC approval demonstrates respect for persons. This paper provides a systematic and comprehensive assessment of why research ethics approval should generally be obtained before publishing in the health promotion context. Journals such as the Health Promotion Journal of Australia have recently begun to require research ethics approval for publishing research. Health promotion researchers will be interested in learning the ethical justification for this change.

We have determined the genomic structure and organization of the mouseCenpaandCenpcgenes. CENPA is a member of the histone H3-like proteins and is thought to replace histone H3 in centromeric nucleosomes. CENPC is a DNA-binding protein that is located at the inner kinetochore plate of active mammalian centromeres. TheCenpacDNA encodes a 134-amino-acid product that is 70% identical and 84% similar to its human homolog. The mouseCenpagene is approximately 8 kb in length and contains five exons. Sequence analysis of the 5′ DNA sequence of the gene revealed two consensus CAAT boxes, a putative TFIID-binding site, an Sp1-binding domain, and two cell cycle regulatory motifs, but no consensus TATA element. The mouseCenpcgene spans 60 kb and contains 19 exons that range in size from 44 to 602 bp. Sequence analysis of the C+G-rich promoter region showed the presence of known promoter elements, including a CpG island, a CAAT box, and several GC boxes, but the absence of a consensus TATA element.

Publics are key stakeholders in population genomic screening and their perspectives on ethical considerations are relevant to programme design and policy making. Using semi-structured interviews, we explored social views and attitudes towards possible future provision of personalised genomic risk information to populations to inform prevention and/or early detection of relevant conditions. Participants were members of the public (n=30) who had received information on their personal genomic risk of melanoma as part of a research project. The focus of the analysis presented here is participants’ views regarding ethical considerations relevant to population genomic screening more generally. Data were analysed thematically and four key themes related to ethical considerations were identified: (i) personal responsibility for health: ‘forewarned is forearmed’; (ii) perceptions of, and responses to, genetic fatalism; (iii) implications for parenting and reproduction; (iv) divided views on choosing to receive genomic risk information. Ethical considerations underlying these themes include the valorisation of information and choice, paternalism, non-directiveness and increasing responsibilisation of individuals in health and healthcare. These findings arguably indicate a thin public conceptualisation of population genomic testing, which draws heavily on how these themes tend to be described in existing social discourses. Findings suggest that further public engagement is required to increase complexity of debate, to consider (for example) the appropriate place of individual and social interests in population genomic testing. Further discernment of relevant ethical approaches, drawing on ethical frameworks from both public health and clinical settings, will also assist in determining the appropriate implementation of population genomic screening for complex conditions.