Context matters in genomic data sharing: a qualitative investigation into responses from the Australian public.

BACKGROUND: Understanding public attitudes to genomic data sharing is widely seen as key in shaping effective governance. However, empirical research in this area often fails to capture the contextual nuances of diverse sharing practices and regulatory concerns encountered in real-world genomic data sharing. This study aimed to investigate factors affecting public attitudes to data sharing through responses to diverse genomic data sharing scenarios. METHODS: A set of seven empirically validated genomic data sharing scenarios reflecting a range of current practices in Australia was used in an open-ended survey of a diverse sample of the Australian public (n = 243). Qualitative responses were obtained for each of the scenarios. Respondents were each allocated one scenario and asked five questions on: whether (and why/not) they would share data; what sharing would depend on; benefits and risks of sharing; risks they were willing to accept if sharing was certain to result in benefits; and what could increase their comfort about sharing and any potential risk. A thematic analysis was used to examine responses, coded and validated by two blinded coders. RESULTS: Participants indicated an overall high willingness to share genomic information, although this willingness varied considerably between different scenarios. A strong perception of benefits was reported as the foremost explanation for willingness to share across all scenarios. The high degree of convergence in the perception of benefits and the types of benefits identified by participants across all the scenarios suggests that the differentiation in intention to share may lie in perceptions of risk, which showed distinct patterns within and between the different scenarios. Some concerns were shared strongly across all scenarios, particularly benefit sharing, future use, and privacy. CONCLUSIONS: Qualitative responses provide insight into popular assumptions regarding existing protections, conceptions of privacy, and which trade-offs are generally acceptable. Our results indicate that public attitudes and concerns are heterogeneous and influenced by the context in which sharing takes place. The convergence of key themes such as benefits and future uses point to core concerns that must be centred in regulatory responses to genomic data sharing.

They Can Have Our Cake - But Can We Eat It? Access to Raw Genomic Data under Australian Privacy Law.

There is an increasing demand for the return of raw genomic data by research participants in translational genomic research. This article discusses the scope and application of privacy and freedom of information legislative provisions in Australia. Whether there is a right to access a copy of such data under Australian privacy legislation is contingent on whether raw genomic data can identify an individual and this article explores the opportunities for genomic data to be linked to individuals. We conclude that despite the complexity and overlapping nature of privacy laws in Australia, there is a clear right on the part of research participants to access their raw genomic data.

Better Mechanisms Are Needed to Oversee HREC Reviews.

Hawe et al. raise concerns about Human Research Ethics Committees (HRECs) taking a risk-averse and litigation-sensitive approach to ethical review of research proposals. HRECs are tasked with reviewing proposals for compliance with the National Statement on Ethical Conduct in Human Research for the purpose of promoting the welfare of participants. While these guidelines intentionally include a significant degree of discretion in HREC decision making, there is also evidence that HRECs sometimes request changes that go beyond the guidance provided by the National Statement. When HRECs request changes outside their remit, inconsistencies between individual HRECs become more common, contributing to delays in ethical review and reducing the quality of HREC decision making. Improvements to the HREC regulatory system are needed to promote transparency and accountability.

Australian human research ethics committee members' confidence in reviewing genomic research applications.

Human research ethics committees (HRECs) are evaluating increasing quantities of genomic research applications with complex ethical considerations. Genomic confidence is reportedly low amongst many non-genetics-experts; however, no studies have evaluated genomic confidence levels in HREC members specifically. This study used online surveys to explore genomic confidence levels, predictors of confidence, and genomics resource needs of members from 185 HRECs across Australia. Surveys were fully or partially completed by 145 members. All reported having postgraduate 94 (86%) and/or bachelor 15 (14%) degrees. Participants consisted mainly of researchers (n = 45, 33%) and lay members (n = 41, 30%), affiliated with either public health services (n = 73, 51%) or public universities (n = 31, 22%). Over half had served their HREC [Formula: see text]3 years. Fifty (44%) reviewed genomic studies [Formula: see text]3 times annually. Seventy (60%) had undertaken some form of genomic education. While most (94/103, 91%) had high genomic literacy based on familiarity with genomic terms, average genomic confidence scores (GCS) were moderate (5.7/10, n = 119). Simple linear regression showed that GCS was positively associated with years of HREC service, frequency of reviewing genomic applications, undertaking self-reported genomic education, and familiarity with genomic terms (p < 0.05 for all). Conversely, lay members and/or those relying on others when reviewing genomic studies had lower GCSs (p < 0.05 for both). Most members (n = 83, 76%) agreed further resources would be valuable when reviewing genomic research applications, and online courses and printed materials were preferred. In conclusion, even well-educated HREC members familiar with genomic terms lack genomic confidence, which could be enhanced with additional genomic education and/or resources.

General practitioners maintain a focus on blood pressure management rather than absolute cardiovascular disease risk management.

BACKGROUND: Absolute cardiovascular disease (aCVD) risk assessment is recommended in CVD prevention guidelines. Yet, General Practitioners (GPs) often focus on single risk factors, including blood pressure (BP). Pathology services may be suitable to undertake high-quality automated unobserved BP (AOBP) measurement and aCVD risk assessment. This study explored GP attitudes towards AOBP measurement via pathology services and the role of BP in aCVD risk management. METHODS: A brief survey was completed, after which a focus group (n = 8 GPs) and interviews (n = 10 GPs) explored attitudes to AOBP and aCVD risk via pathology services with an example pathology report discussed. Verbatim transcripts were thematically coded. RESULTS: GPs predominantly used doctor-measured BP despite low levels of confidence. High BP measured by AOBP reported with aCVD risk via pathology services, would prompt a follow-up response. However, GPs focused on BP management. GPs were concerned about AOBP equivalency to routine BP measurements. After protocol explanation, GPs reported AOBP could value-add to care delivery. CONCLUSION: GPs lacked familiarity of AOBP and maintained a focus on BP management in the context of absolute CVD risk. Targeted education on AOBP and BP management as part of absolute CVD risk is needed to support guideline-directed care in practice.

General practitioner perceptions of assessment and reporting of absolute cardiovascular disease risk via pathology services: a qualitative study.

BACKGROUND: Guidelines for cardiovascular disease (CVD) prevention recommend assessment of absolute CVD risk to guide clinical management. Despite this, use among general practitioners (GPs) remains limited. OBJECTIVE: Pathology services may provide an appropriate setting to assess and report absolute CVD risk in patients attending for cholesterol measurement. This study aimed to explore GPs perceptions of such a service. METHODS: A focus group and semi-structured interviews were conducted with GPs (n = 18) in Tasmania, Australia, to identify perceptions of assessment and reporting of absolute CVD risk via pathology services. An example pathology report including absolute CVD risk was provided and discussed. Audio-recordings were transcribed and thematically coded by two researchers. RESULTS: Almost all GPs identified that absolute CVD risk assessed and reported via pathology services could address deficits in practice. First, by reducing the number of appointments required to collect risk factors. Second, by providing a systematic (rather than opportunistic) approach for assessment of absolute CVD risk. Third, by reducing misclassification of patient CVD risk caused by overreliance on clinical intuition. All GPs reported they would order absolute CVD risk when issuing a cholesterol referral if such a service was offered. GPs recommended improving the service by providing information on methods used to measure risk factors on the pathology report. CONCLUSIONS: Absolute CVD risk assessed and reported via pathology services may address challenges of screening CVD risk experienced by GPs in practice and encourage dedicated follow-up care for CVD prevention.

Cerebral small vessel disease genomics and its implications across the lifespan.

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5×10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.

Equitable Expanded Carrier Screening Needs Indigenous Clinical and Population Genomic Data.

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.

Self-directed multimedia process for delivering participant informed consent.

OBJECTIVE: Obtaining informed consent is a cornerstone requirement of conducting ethical research. Traditional paper-based consent is often excessively lengthy and may fail to achieve the desired participant understanding of study requirements. Multimedia tools including video and audio may be a useful alternative. This study aimed to determine the efficacy, usability and acceptability of self-directed multimedia delivery of participant consent. DESIGN: It is a single-centre, randomised, prospective study to determine the efficacy, usability and acceptability of a self-directed multimedia consent process (intervention) compared with the traditional paper-based approach (control). The intervention was free of research staff, with computer-based finger-signed consent. SETTING: Pathology blood collection services in Tasmania, Australia. PARTICIPANTS: 298 participants (63±8 years; 51% female individuals) referred from general practice were randomised to intervention (n=146) and control (n=152). OUTCOME MEASURES: Efficacy, usability and acceptability of the allocated consent process were assessed by a questionnaire. RESULTS: All participants successfully completed the allocated interventions. Efficacy parameters were higher among intervention participants, including a better understanding of study requirements compared with controls (p<0.05 all). Intervention participants were more likely to engage with the study information and spend more time on the consent process (p=<0.001 and p=0.006, respectively). Both groups reported similar levels of acceptability, although more control participants reported that the study information was too long (24% vs 14%; p=0.020). CONCLUSION: A self-directed multimedia consent process is effective for achieving participant understanding and obtaining consent free of research staff. Thus, multimedia represents a viable method to reduce the burden on researchers, meet participant needs and achieve informed consent in clinical research.

A Scenario-Based Methodology for Analyzing the Ethical, Legal, and Social Issues in Genomic Data Sharing.

Sharing of genomic and associated data is essential to clinical practice and biomedical research, and is increasingly encouraged by journals and funding bodies. Grappling with the range of legal and ethical issues raised by genomic data sharing presents a significant challenge, given the diversity of practices: from defined sharing of individual patient data, to broad-scale public sharing of research data, to uploading of direct-to-consumer test data by community members. Most commentary to date has discussed these issues in broad terms, but the debate can only progress if we engage with more granularity, grounded in jurisdictional and contextual specifics. We developed an empirical approach, creating a set of prototypical scenarios that capture the diversity of current genomic data sharing practices, which allows legal and ethical analysis of key issues at a granular level. The specificity of this approach provides a strong foundation for developing useful and relevant regulatory recommendations.

Integration of absolute cardiovascular disease risk assessment into routine blood cholesterol testing at pathology services.

BACKGROUND: Absolute cardiovascular disease (CVD) risk assessment is recommended for primary prevention of CVD, yet uptake in general practice is limited. Cholesterol requests at pathology services provide an opportunity to improve uptake by integrating absolute CVD risk assessment with this service. OBJECTIVE: This study aimed to assess the feasibility of such an additional service. METHODS: Two-hundred and ninety-nine patients (45-74 years) referred to pathology services for blood cholesterol had measurement of all variables required to determine absolute CVD risk according to Framingham calculator (blood pressure, age, sex, smoking and diabetes status via self-report). Data were recorded via computer-based application. The absolute risk score was communicated via the report sent to the referring medical practitioner as per usual practice. Evaluation questionnaires were completed immediately post visit and at 1-, 3- and 6-month follow-up via telephone (n = 262). RESULTS: Absolute CVD risk reports were issued for 90% of patients. Most patients (95%) reported that the length of time for the pathology service assessment was acceptable, and 91% that the self-directed computer-based application was easy to use. Seventy-eight per cent reported a preference for pathology services to conduct absolute CVD risk assessment. Only 2% preferred a medical practitioner. Of follow-up patients, 202 (75%) had a consultation with a medical practitioner, during which, aspects of CVD risk prevention were discussed (cholesterol and blood pressure 74% and 69% of the time, respectively). CONCLUSIONS: Measurement of absolute CVD risk in pathology services is feasible, highly acceptable among middle-to-older adults and may increase uptake of guideline-directed care in general practice.

Recurrence patterns identify aggressive form of human papillomavirus-dependent vulvar cancer.

BACKGROUND: Vulvar cancer is rare and, as a result, is understudied. Treatment is predominantly surgery, irrespective of the type of vulvar cancer, and is associated with physical, emotional and sexual complications. A cluster of human papillomavirus (HPV)-dependent vulvar cancer patients was identified in Arnhem Land Northern Territory (NT), Australia, in which young Indigenous women were diagnosed at 70 times the national incidence rate. AIMS: To assess whether women from the Arnhem Land cluster differ from women with vulvar squamous cell carcinoma (VSCC) and vulvar intraepithelial neoplasia (VIN) resident elsewhere in the NT in recurrence after treatment, disease progression and mortality. MATERIALS AND METHODS: A retrospective cohort study of NT-resident women diagnosed with VIN or invasive vulvar cancer (VSCC) between 1 January 1993 and 30 June 2015 was undertaken. Time to recurrence was assessed using cumulative incidence plots and Fine and Gray competing risk regression models. Mean cumulative count was used to estimate the burden of recurrent events. RESULTS: Indigenous women from Arnhem Land experienced more recurrences after treatment than non-Indigenous women, the cancers recurred faster, and Indigenous women have worse survival at five years. CONCLUSIONS: In characterising the epidemiological features of this cluster, we have identified a particularly aggressive form of vulvar cancer. This provides a unique opportunity for elucidating the aetiopathological pathways driving vulvar cancer development that may ultimately lead to preventive and therapeutic targets for this neglected malignancy. Further, these findings have important implications for clinical practice and HPV vaccination policy in the affected population.

Disclosure of Genetic Results to At-risk Relatives without Consent: Issues for Health Care Professionals in Australia.

Disclosure of genetic information without consent of the patient (proband) challenges the legal frameworks of privacy and confidentiality. Changes to privacy legislation enable and provide guidelines for undertaking disclosure, with the purpose of reducing the harm to genetic relatives who, armed with such information, may seek predictive testing themselves. Nevertheless, significant uncertainty remains for health care professionals in the application of the discretion to disclose genetic information to at-risk relatives. First, jurisdictional inconsistencies in privacy legislation present challenges for the provision of genetic services across the country. Second, the current guidelines provide insufficient clarity regarding the justification for disclosure of genetic information to reduce psychological harm to relatives. Third, the implications of a potential expansion of a legal duty of care to inform genetic relatives in some circumstances indicates that such a duty would be unduly burdensome for health care professionals, and suggests that revision of the threshold for use - rather than disclosure - of depersonalised genetic information may represent a pragmatic way forward.

Australia: regulating genomic data sharing to promote public trust.

The regulation of genomic data sharing in Australia is a confusing mix of common law, legislation, ethical guidelines, and codes of practice. Beyond privacy laws, which only apply to genomic data that meets the definition of personal information, the key regulatory lever is the National Health and Medical Research Council (NHMRC) National Statement for Ethical Conduct in Human Research ("National Statement") (2007). Compliance with the National Statement is a requirement for institutions to apply to the NHMRC for funding, and includes-among other things-requirements for review of most genomic research by Human Research Ethics Committees. The sections of the National Statement specifying requirements for research with human genomic data are currently under review, including proposed new requirements addressing the return of genetic research findings and oversight of transfer agreements. Ensuring the willingness of Australians to donate their genomic information and participate in medical research will require clarification and harmonisation of the applicable regulatory framework, along with reforms to ensure that these regulations reflect the conditions necessary to promote ongoing public trust in researchers and institutions.

Provenance and risk in transfer of biological materials.

Whereas biological materials were once transferred freely, there has been a marked shift in the formalisation of exchanges involving these materials, primarily through the use of Material Transfer Agreements (MTAs). This paper considers how risk aversion dominates MTA negotiations and the impact it may have on scientific progress. Risk aversion is often based on unwarranted fears of incurring liability through the use of a material or loss of control or missing out on commercialisation opportunities. Evidence to date has suggested that complexity tends to permeate even straightforward transactions despite extensive efforts to implement simple, standard MTAs. We argue that in most cases, MTAs need do little more than establish provenance, and any attempt to extend MTAs beyond this simple function constitutes stifling behaviour. Drawing on available examples of favourable practice, we point to a number of strategies that may usefully be employed to reduce risk-averse tendencies, including the promotion of simplicity, education of those engaged in the MTA process, and achieving a cultural shift in the way in which technology transfer office (TTO) success is measured in institutions employing MTAs.

Correction to: Australia: regulating genomic data sharing to promote public trust.

This article was inadvertently published under a draft title.

Moving Forward on Consent Practices in Australia.

Allowing persons to make an informed choice about their participation in research is a pre-eminent ethical and legal requirement. Almost universally, this requirement has been addressed through the provision of written patient information sheets and consent forms. Researchers and others have raised concerns about the extent to which such forms-particularly given their frequent lengthiness and complexity-provide participants with the tools and knowledge necessary for autonomous decision-making. Concerns are especially pronounced for certain participant groups, such as persons with low literacy and Indigenous persons. Multimedia strategies have the potential to usefully supplement current consent practices in Australia; however, information is needed about the need for supplementary consent practices, along with drivers for and barriers against adoption. This study initiates the required evidence base through an audit of informed consent practices for medical research in the Australian state of Tasmania to assess the need for, and current uptake of, supplementary consent strategies. Drivers for and barriers against adoption of multimedia consent practices were explored in detail through interviews with key stakeholders, including researchers, HREC chairs and members, and research participants, including Indigenous participants.

Regulation of unregistered birth workers in Australia: Homebirth and public safety.

BACKGROUND: Australian midwives are regulated under the National Registration and Accreditation Scheme. Unregistered birth workers may provide midwifery services at homebirths without any regulatory oversight. To address this issue, several states have passed legislation enabling prohibition orders to be made (negative licensing) against unregistered health practitioners who fail to comply with a statutory code of conduct developed for those not covered by the National Scheme. AIM: To explore the consequences for the availability of birth choices for women that arise from the introduction of negative licensing. DISCUSSION: An analysis of the regulatory framework and recent cases of unregistered birth workers attending homebirths reveals problems with equitable access to homebirth support, arising from issues with professional indemnity insurance, geography, and poor integration with hospitals and the wider healthcare system. These problems contribute to women choosing to employ the services of unregistered birth workers. CONCLUSION: Negative licensing provides a useful additional tool for improving the safety of homebirths for mothers and babies, but it does not address the issues leading expectant parents to choose an unregistered birth worker to attend their births, and may contribute to an increase in high-risk behaviours, such as freebirthing.

Key challenges in bringing CRISPR-mediated somatic cell therapy into the clinic.

Genome editing using clustered regularly interspersed short palindromic repeats (CRISPR) and CRISPR-associated proteins offers the potential to facilitate safe and effective treatment of genetic diseases refractory to other types of intervention. Here, we identify some of the major challenges for clinicians, regulators, and human research ethics committees in the clinical translation of CRISPR-mediated somatic cell therapy.