Beyond severity: utility as a criterion for setting the scope of RGCS.

Reproductive genetic carrier screening (RGCS) allows prospective parents to identify and act upon their chances of having a child with a genetic condition. In deciding which genetic conditions to include in RGCS, severity is often used as a criterion. However, the concept is inherently complex, subjective and multidimensional, and determinations of severity will remain intractably contested. We propose the concept of utility as a criterion for setting the scope of RGCS, and put forward two central arguments for doing so. First, utility is a more appropriate and effective concept as it responds to context and makes an explicit connection between the purpose of RGCS and the value of information obtained for that purpose: namely, to facilitate reproductive decision-making. Utility comprises both clinical and personal utility, and varies according to the availability and accessibility of reproductive options, including pre-implantation genetic testing, prenatal genetic diagnosis, and termination of pregnancy. Second, there are ethical reasons for preferring utility over severity. Utility is a property of the information gleaned from RGCS, while severity is a property of a genetic condition or of an instance of this condition in a person. While consideration of the severity of genetic conditions is not lost when focusing on utility, the need to rely on value judgements regarding the quality of life of people who live with genetic conditions is circumvented. Therefore, utility should replace severity as justification for the inclusion of genetic conditions in RGCS programmes.

Is It Just for a Screening Program to Give People All the Information They Want?

Genomic screening at population scale generates many ethical considerations. One is the normative role that people's preferences should play in determining access to genomic information in screening contexts, particularly information that falls beyond the scope of screening. We expect both that people will express a preference to receive such results and that there will be interest from the professional community in providing them. In this paper, we consider this issue in relation to the just and equitable design of population screening programs like reproductive genetic carrier screening (RGCS). Drawing on a pluralistic public health ethics perspective, we claim that generating and reporting information about genetic variants beyond the scope of the screening program usually lacks clinical, and perhaps personal, utility. There are both pragmatic and ethical reasons to restrict information provision to that which fits the stated purpose of the program.

How should severity be understood in the context of reproductive genetic carrier screening?

Reproductive genetic carrier screening provides information about people's chance of having children with certain genetic conditions. Severity of genetic conditions is an important criterion for their inclusion in carrier screening programmes. However, the concept of severity is conceptually complex and underspecified. We analyse why severity is an important concept in carrier screening and for reproductive decision-making and show that assessments of severity can also have normative societal implications. While some genetic conditions are unambiguously associated with a high degree of suffering, there are many factors that contribute to how severe a condition is perceived to be, and perspectives will vary. Attempts to classify genetic conditions according to their severity tend to prioritise biomedical information at the expense of incorporating qualitative aspects of the impact of genetic conditions on people's lives. Further complexity arises because some genotypes can present with variable phenotypes and because some conditions are not always experienced in the same way by all people who have them. To acknowledge this complexity, we argue that an understanding of severity needs to distinguish between the severity of a genetic condition-requiring a generalised approach for purposes of policy development and programme design-and the severity of an instance of a genetic condition in a particular person. Families making reproductive decisions also require access to diverse experiences of the qualitative aspects of living with genetic conditions. As a result, reproductive carrier screening programmes must recognise and respond to the complexity inherent in determining the severity of genetic conditions.

The Australian Reproductive Genetic Carrier Screening Project (Mackenzie's Mission): Design and Implementation.

Reproductive genetic carrier screening (RGCS) provides people with information about their chance of having children with autosomal recessive or X-linked genetic conditions, enabling informed reproductive decision-making. RGCS is recommended to be offered to all couples during preconception or in early pregnancy. However, cost and a lack of awareness may prevent access. To address this, the Australian Government funded Mackenzie's Mission­the Australian Reproductive Genetic Carrier Screening Project. Mackenzie's Mission aims to assess the acceptability and feasibility of an easily accessible RGCS program, provided free of charge to the participant. In study Phase 1, implementation needs were mapped, and key study elements were developed. In Phase 2, RGCS is being offered by healthcare providers educated by the study team. Reproductive couples who provide consent are screened for over 1200 genes associated with >750 serious, childhood-onset genetic conditions. Those with an increased chance result are provided comprehensive genetic counseling support. Reproductive couples, recruiting healthcare providers, and study team members are also invited to complete surveys and/or interviews. In Phase 3, a mixed-methods analysis will be undertaken to assess the program outcomes, psychosocial implications and implementation considerations alongside an ongoing bioethical analysis and a health economic evaluation. Findings will inform the implementation of an ethically robust RGCS program.

Ethical aspects of the changing landscape for spinal muscular atrophy management in Australia.

BACKGROUND: New methods of detecting and treating spinal muscular atrophy (SMA) are now available, and the Australian SMA landscape is rapidly changing. These various interventions can be increasingly complex to navigate for both healthcare professionals and at-risk families. OBJECTIVE: The aim of this article is to describe how recent developments in SMA testing and treatment give rise to ethical considerations. DISCUSSION: Ethical issues in SMA detection and treatment arise for both individual interventions and how they integrate. A patient-centred approach can help general practitioners to navigate these issues.

Ethical considerations in gene selection for reproductive carrier screening.

Genetic carrier screening for reproductive purposes has existed for half a century. It was originally offered to particular ethnic groups with a higher prevalence of certain severe recessive or X-linked genetic conditions, or (as carrier testing) to those with a family history of a particular genetic condition. Commercial providers are increasingly offering carrier screening on a user-pays basis. Some countries are also trialing or offering public reproductive genetic carrier screening with whole populations, rather than only to those known to have a higher chance of having a child with an inherited genetic condition. Such programs broaden the ethical and practical challenges that arise in clinical carrier testing. In this paper we consider three aspects of selecting genes for population reproductive genetic carrier screening panels that give rise to important ethical considerations: severity, variable penetrance and expressivity, and scalability; we also draw on three exemplar genes to illustrate the ethical issues raised: CFTR, GALT and SERPINA1. We argue that such issues are important to attend to at the point of gene selection for RGCS. These factors warrant a cautious approach to screening panel design, one that takes into account the likely value of the information generated by screening and the feasibility of implementation in large and diverse populations. Given the highly complex and uncertain nature of some genetic variants, careful consideration needs to be given to the balance between delivering potentially burdensome or harmful information, and providing valuable information to inform reproductive decisions.

Reproductive carrier screening: responding to the eugenics critique.

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.

From a Right to a Preference: Rethinking the Right to Genomic Ignorance.

The "right not to know" has generated significant discussion, especially regarding genetic information. In this paper, I argue that this purported right is better understood as a preference and that treating it as a substantive right has led to confusion. To support this claim, I present three critiques of the way the right not to know has been characterized. First, I demonstrate that the many conceptualizations of this right have hampered debate. Second, I show that the way autonomy is conceptualized in this literature is also problematic. Third, I examine the notion of a right in more detail, to support my third critique: that the right to know and the right not to know genetic information are often erroneously treated as having equivalent status. On my understanding, the claim being made is better thought of as a preference, not a right, and a preference not to know certain information becomes only one of several considerations relevant to medical decision making.

Ethics of Reproductive Genetic Carrier Screening: From the Clinic to the Population.

Reproductive genetic carrier screening (RCS) is increasingly being offered more widely, including to people with no family history or otherwise elevated chance of having a baby with a genetic condition. There are valid reasons to reject a prevention-focused public health ethics approach to such screening programs. Rejecting the prevention paradigm in this context has led to an emphasis on more individually-focused values of freedom of choice and fostering reproductive autonomy in RCS. We argue, however, that population-wide RCS has sufficient features in common with other public health screening programs that it becomes important also to attend to its public health implications. Not doing so constitutes a failure to address the social conditions that significantly affect people's capacity to exercise their reproductive autonomy. We discuss how a public health ethics approach to RCS is broader in focus than prevention. We also show that additional values inherent to ethical public health-such as equity and solidarity-are essential to underpin and inform the aims and implementation of reproductive carrier screening programs.

Beyond platitudes: a qualitative study of Australian Aboriginal people's perspectives on biobanking.

BACKGROUND: Biobanks are vital resources for genetics and genomics, and it is broadly recognised that for maximal benefit it is essential that they include samples and data from diverse ancestral groups. The inclusion of First Nations people, in particular, is important to prevent biobanking research from exacerbating existing health inequities, and to ensure that these communities share in the benefits arising from research. AIMS: To explore the perspectives of Australian Aboriginal people whose tissue - or that of their family members - has been stored in the biobank of the National Centre for Indigenous Genomics (NCIG). METHODS: Semi-structured interviews with 42 Aboriginal people from the Titjikala, Galiwinku, Tiwi Islands, Yarrabah, Fitzroy Crossing, Derby, One Arm Point and Mulan communities, as well as a formal discussion with A. Hermes, an Indigenous Community Engagement Coordinator at the NCIG who had conducted the interviews. The interviews and the structured discussion were double coded using a procedure informed by Charmaz's outline of grounded theory analysis and Morse's outline of the cognitive basis of qualitative research. RESULTS: In this article, we report on A. Hermes' interviews with members from the above Aboriginal communities, as well as on her personal views, experiences, and interpretations of the interviews she conducted with other community members. We found that participation in the NCIG biobank raised issues around broken trust, grief and loss, but also - somewhat unexpectedly - was perceived as a source of empowerment, hope and reconnection. CONCLUSIONS: This research reminds us (again) of the need to engage deeply with communities in order to respond appropriately with respect for their cultural values and norms, and to develop culturally relevant policies and processes that enhance the benefits of biobank participation and minimise potential harms.

Biobank networking and globalisation: perspectives and practices of Australian biobanks.

Objective This study examined the practices and attitudes of Australian biobanks regarding access to samples and data, as well as local and global networking with other biobanks. Methods This was a mixed-methods study, including an online survey of Australian biobank administrators and qualitative interviews with survey participants. The survey examined the criteria applied when considering requests to share or network. The interviews explored attitudes and practices regarding sharing and networking. Results Most (90.9%; 30/33) biobanks offered access to their samples and data to others, principally for research (90.6%; 29/32). The most common criteria used to evaluate access requests included ethical oversight (84.8%; 28/33), scientific merit (84.8%; 28/33) and intended use (81.8%; 27/33). Just over two-thirds (69.7%; 23/33) of biobanks participated in Australian networks, and 39.1% (9/23) participated in global networks. Networking took the form of both sharing standardised operating procedures and policies (60.9%) and sharing samples and data (43.5%). Thirteen of the 16 interviewees participated in networks. Motivations for sharing included scientific necessity, sharing expertise and standardising operations and governance. Significant barriers to networking remain, including insufficient resources, inconsistent regulations and procedures, and cultural and political issues to do with the conduct of research. Conclusions Many Australian biobanks are already active participants in various types of global biobanking. If biobanks are to expand and make the most of their involvement in global networks, then important barriers need to be overcome. What is known about the topic? Biobanks that store human tissue and associated data are increasingly forming local, national and global networks. These networks create opportunities for enhancing the utility and sustainability of biobanks, but also raise considerable technical, legal and ethical challenges. What does this paper add? This paper reports findings from a mixed-methods study of Australian biobanks and reveals contemporary practices and perspectives concerning sample and data sharing, as well as local and global networking. It found most Australian biobanks currently take part in these activities. What are the implications for practitioners? Many Australian biobanks are networking in various ways across regional and national borders. A better understanding of current practices and views on significant and emerging issues is relevant to the diverse range of biobank stakeholders involved in any agenda to expand biobank networking, including patients, consumers, clinicians, scientists, policy makers and regulators.

Examining diversity in public willingness to participate in offshore human biobanking: An Australian mixed methods study.

To ensure their sustainability and scientific utility, human biobanks are networking internationally. Sharing biospecimens and associated data across jurisdictions raise a number of practical, ethical, legal and social challenges that could reduce the publics' willingness to donate their much needed tissue for research purposes. This research aims to identify the impact of biobank location on willingness to donate through a national quantitative survey (n = 750) and 16 in-depth interviews. A latent class analysis in combination with qualitative results suggests that a large proportion of Australians are willing to donate and/or allow their tissue to be stored offshore to help others, but others are reluctant due to uncertainty around foreign ethical and regulatory standards and the loss of potential local benefits. The results highlight for the first time the diversity of public views, and provide important guidance for policy makers and science communicators eager to tailor strategies for specific publics.