The Deceased, Public Health, and Research: Proposing Legal Reforms.

There is little guidance concerning biomedical research using tissues from deceased individuals. Unique ethical and legal challenges gained visibility during the coronavirus disease 2019 (COVID-19) pandemic, when important studies using genome sequencing required access to biological materials from deceased individuals. These studies proposed to determine whether specific genomic profiles were associated with important disease outcomes. Such research has previously required consent from next-of-kin or other surrogate decision makers. Ethics waivers for such consent vary within Canada. In Ontario, research ethics boards can grant waivers of consent if the Tri-Council Policy Statement-2 conditions are met. These include that the individual is not harmed, that the materials are essential to the research, and that privacy will be protected. Conversely, in Quebec, Civil Code article 22 imposes an obligation on researchers to seek consent from next-of-kin or another surrogate decision maker with no option for waivers. It became evident to researchers that these standards can sometimes impose an impracticable balance of risks and benefits, especially in public health emergencies. We seek to establish why and when consent requirements should be waived for public health and research involving the tissues of deceased individuals.

Canadian Healthcare Professionals' Views and Attitudes toward Risk-Stratified Breast Cancer Screening.

Given the controversy over the effectiveness of age-based breast cancer (BC) screening, offering risk-stratified screening to women may be a way to improve patient outcomes with detection of earlier-stage disease. While this approach seems promising, its integration requires the buy-in of many stakeholders. In this cross-sectional study, we surveyed Canadian healthcare professionals about their views and attitudes toward a risk-stratified BC screening approach. An anonymous online questionnaire was disseminated through Canadian healthcare professional associations between November 2020 and May 2021. Information collected included attitudes toward BC screening recommendations based on individual risk, comfort and perceived readiness related to the possible implementation of this approach. Close to 90% of the 593 respondents agreed with increased frequency and earlier initiation of BC screening for women at high risk. However, only 9% agreed with the idea of not offering BC screening to women at very low risk. Respondents indicated that primary care physicians and nurse practitioners should play a leading role in the risk-stratified BC screening approach. This survey identifies health services and policy enhancements that would be needed to support future implementation of a risk-stratified BC screening approach in healthcare systems in Canada and other countries.

Concordance of International Regulation of Pediatric Health Research.

OBJECTIVE: To assess the comparability of international ethics principles and practices used in regulating pediatric research as a first step in determining whether reciprocal deference for international ethics review is feasible. Prior studies by the authors focused on other aspects of international health research, such as biobanks and direct-to-participant genomic research. The unique nature of pediatric research and its distinctive regulation by many countries warranted a separate study. STUDY DESIGN: A representative sample of 21 countries was selected, with geographical, ethnic, cultural, political, and economic diversity. A leading expert on pediatric research ethics and law was selected to summarize the ethics review of pediatric research in each country. To ensure the comparability of the responses, a 5-part summary of pediatric research ethics principles in the US was developed by the investigators and distributed to all country representatives. The international experts were asked to assess and describe whether principles in their country and the US were congruent. Results were obtained and compiled in the spring and summer of 2022. RESULTS: Some of the countries varied in their conceptualization or description of one or more ethical principles for pediatric research, but overall, the countries in the study demonstrated a fundamental concordance. CONCLUSIONS: Similar regulation of pediatric research in 21 countries suggests that international reciprocity is a viable strategy.

Data and Tools Integration in the Canadian Open Neuroscience Platform.

We present the Canadian Open Neuroscience Platform (CONP) portal to answer the research community's need for flexible data sharing resources and provide advanced tools for search and processing infrastructure capacity. This portal differs from previous data sharing projects as it integrates datasets originating from a number of already existing platforms or databases through DataLad, a file level data integrity and access layer. The portal is also an entry point for searching and accessing a large number of standardized and containerized software and links to a computing infrastructure. It leverages community standards to help document and facilitate reuse of both datasets and tools, and already shows a growing community adoption giving access to more than 60 neuroscience datasets and over 70 tools. The CONP portal demonstrates the feasibility and offers a model of a distributed data and tool management system across 17 institutions throughout Canada.

Open Data in the Era of the GDPR: Lessons from the Human Cell Atlas.

The Human Cell Atlas (HCA) is striving to build an open community that is inclusive of all researchers adhering to its principles and as open as possible with respect to data access and use. However, open data sharing can pose certain challenges. For instance, being a global initiative, the HCA must contend with a patchwork of local and regional privacy rules. A notable example is the implementation of the European Union General Data Protection Regulation (GDPR), which caused some concern in the biomedical and genomic data-sharing community. We examine how the HCA's large, international group of researchers is investing tremendous efforts into ensuring appropriate sharing of data. We describe the HCA's objectives and governance, how it defines open data sharing, and ethico-legal challenges encountered early in its development; in particular, we describe the challenges prompted by the GDPR. Finally, we broaden the discussion to address tools and strategies that can be used to address ethical data governance.

Mitochondrial Replacement Therapy: In Whose Interests?

Mitochondrial replacement therapy (MRT), also called nuclear genome transfer and mitochondrial donation, is a new technique that can be used to prevent the transmission of mitochondrial DNA diseases. Apart from the United Kingdom, the first country to approve MRT in 2015, Australia became the second country with a clear regulatory path for the clinical applications of this technique in 2021. The rapidly evolving clinical landscape of MRT makes the elaboration and evaluation of the responsible use of this technology a pressing matter. As jurisdictions with less strict or non-existent reproductive laws are continuing to use MRT in the clinical context, the need to address the underlying ethical issues surrounding MRT's clinical translation is fundamental.

Bridging the European Data Sharing Divide in Genomic Science.

In this viewpoint, we argue for the importance of creating data spaces for genomic research that are detached from contexts in which fundamental rights concerns related to surveillance measures override a purpose-specific balancing of fundamental rights. Genomic research relies on molecular and phenotypic data, on comparing findings within large data sets, on searchable metadata, and on translating research results into a clinical setting. These methods require sensitive genetic and health data to be shared across borders. International data sharing between the European Union (EU) or the European Economic Area and third countries has accordingly become a cornerstone of genomics. The EU General Data Protection Regulation contains rules that accord privileged status to data processing for research purposes to ensure that strict data protection requirements do not impede biomedical research. However, the General Data Protection Regulation rules applicable to international transfers of data accord no such preferential treatment to international data transfers made in the research context. The rules that govern the international transfer of data create considerable barriers to international data sharing because of the cost-intensive procedural and substantive compliance burdens that they impose. For certain jurisdictions and select use cases, there exist practically no lawful mechanisms to enable the international transfer of data because of concerns about the protection of fundamental rights. The proposed solutions further fail to address the need to share large data sets of local and regional cohorts across national borders to enable joint analyses. The European Health Data Space is an emerging federated, EU-wide data infrastructure that is intended to function as an infrastructure bringing together EU health data to improve patient care and enable the secondary use of health-related data for research purposes. Such infrastructure is implementing new institutions to support its functioning and is being implemented in reliance on a new enabling law, the regulation on the European Health Data Space. This innovation provides the opportunity to facilitate EU contribution to international genomic research efforts. The draft regulation for this data space provides for a concept of data infrastructure intended to enable cross-border data exchange and access, including access to genetic and health data for scientific analysis purposes. The draft regulation also provides for obligations of national actors aimed at making data widely available. This effort is laudable. However, in the absence of further, more fundamental changes to the manner in which the EU regulates the secondary use of health data, it is reasonable to believe that EU participation in international genomic research efforts will remain impeded.

Polygenic risk scores and risk-stratified breast cancer screening: Familiarity and perspectives of health care professionals.

PURPOSE: Health care professionals are expected to take on an active role in the implementation of risk-based cancer prevention strategies. This study aimed to explore health care professionals' (1) self-reported familiarity with the concept of polygenic risk score (PRS), (2) perceived level of knowledge regarding risk-stratified breast cancer (BC) screening, and (3) preferences for continuing professional development. METHODS: A cross-sectional survey was conducted using a bilingual-English/French-online questionnaire disseminated by health care professional associations across Canada between November 2020 and May 2021. RESULTS: A total of 593 professionals completed more than 2 items and 453 responded to all questions. A total of 432 (94%) participants were female, 103 (22%) were physicians, and 323 (70%) were nurses. Participants reported to be unfamiliar with (20%), very unfamiliar (32%) with, or did not know (41%) the concept of PRS. Most participants reported not having enough knowledge about risk-stratified BC screening (61%) and that they would require more training (77%). Online courses and webinar conferences were the preferred continuing professional development modalities. CONCLUSION: The study indicates that health care professionals are currently not familiar with the concept of PRS or a risk-stratified approach for BC screening. Online information and training seem to be an essential knowledge transfer modality.

Sharing and Safeguarding Pediatric Data.

Data sharing is key to advancing our understanding of human health and well-being. While issues related to pediatric research warrant strong ethical protections, overly protectionist policies may serve to exclude minors from data sharing initiatives. Pediatric data sharing is critical to scientific research concerning health and well-being, to say nothing of understanding human development generally. For example, large-scale pediatric longitudinal studies, such as those in the DREAM-BIG Consortium, on the influence of prenatal adversity factors on child psychopathology, will provide prevention data and generate future health benefits. Recent initiatives have formulated sound policy to help enable and foster data sharing practices for pediatric research. To help translate these policy initiatives into practice, we discuss how model consent clauses for pediatric research can help address some of the issues and challenges of pediatric data sharing, while enabling data sharing.

The international data governance landscape.

As the adoption of digital health accelerates health research increasingly relies on large quantities of biomedical data. Research institutions scattered across a large number of jurisdictions collaborate in producing and analyzing biomedical big data. National data protection legislation, for its part, grows increasingly complex and localized. To respond to heterogeneous legal requirements arising in numerous jurisdictions, decentralized health consortia must develop scalable organizational and 6 technological arrangements that enable data flows across jurisdictional boundaries. In this article, proposals are made to enable health sector organisations to align established biomedical ethics process and data analysis practices to shifting data protection norms through both public law co-regulation, private law tools, and design-oriented approaches.

"The Stakes Are Higher"- Patient and Caregiver Perspectives on Cystic Fibrosis Research and Personalized Medicine.

Introduction: Making bench to bedside advances in cystic fibrosis (CF) care requires the sustained engagement and trust of people living with CF. However, there is a scarcity of studies exploring their concerns and priorities regarding research and its end products. The aim of this qualitative study was to generate empirical evidence regarding patient and caregiver perspectives on cystic fibrosis research and personalized medicine to foster developments in translational research in Canada. Methods: A total of 15 focus groups were conducted, engaging 22 adults with CF and 18 caregivers (e.g., parents, siblings and partners) living in Canada. Inductive thematic analysis relied on an iterative process involving themes derived from both participant meaning-making and existing scientific literature. Participant perspectives were considered along intrapersonal, intracommunity, interpersonal, and structural lines. Results: Overall, participants described a relationship to CF research inextricable from the lived experience of CF as a lifelong progressive and terminal disease and from the goal of advancing medical science. They were enthusiastic and excited about the emergence of CFTR modulators, although they had some knowledge gaps regarding the associated research. They largely spoke to positive experiences with researcher communication but had feedback regarding informed consent processes and the return of study results. Participants also voiced concerns about structural access barriers to research and to its end products. Extensive histories of research participation, a relatively small and intercommunicative CF community, and structural overlap between research and care settings contributed to their perspectives and priorities. Conclusion: Study findings are valuable for researchers and policy-makers in CF and rare or progressive diseases more broadly. Continuing to solicit and listen to the voices of patients and caregivers is crucial for research ethics and the translation of new therapies in the area of personalized medicine.

Streamlining ethics review for international health research.

Single-site review means protection and efficiency.

Ethical challenges of precision cancer medicine.

Amongst common diseases, cancer is often both a leader in self-regulatory policy, or the field for contentious ethical issues such as the patenting of the BRCA1/2 genes. With the advent of genomic sequencing technologies, achieving precision cancer medicine requires prospective norms due to the large and varied sources of data involved. Here, we discuss the ethical and legal aspects of the policy debate around the relevant topics in precision cancer medicine: the return of incidental findings and sequencing raw data to patients, the communication of genetic results to patients' relatives, privacy and communication risks with concomitant oversight strategies, patient participation and consent models. We present the arguments and empirical data supporting specific policy solutions delineating still contested areas. What type of consent and oversight are required to acquire genomic data or to access it where desired, either by the participant/patient or third-party researchers? Most of the raw sequencing data is still uninterpretable and the variants revealed subject to reinterpretation over time. No doubt the ethical challenges of precision cancer medicine are a prototype of what's to come for other diseases. They are also paradigmatic for regulatory and ethical questions of the translational endeavors since the two worlds - basic science and patient care - are governed by different ethical and legal principles that need to be reconciled in precision cancer medicine.

Artificial Intelligence in Cardiovascular Imaging: "Unexplainable" Legal and Ethical Challenges?

Nowhere is the influence of artificial intelligence (AI) likely to be more profoundly felt than in health care, from patient triage and diagnosis to surgery and follow-up. Over the medium-term, these effects will be more acute in the cardiovascular imaging context, in which AI models are already successfully performing at approximately human levels of accuracy and efficiency in certain applications. Yet, the adoption of unexplainable AI systems for cardiovascular imaging still raises significant legal and ethical challenges. We focus in particular on challenges posed by the unexplainable character of deep learning and other forms of sophisticated AI modelling used for cardiovascular imaging by briefly outlining the systems being developed in this space, describing how they work, and considering how they might generate outputs that are not reviewable by physicians or system programmers. We suggest that an unexplainable tendency presents 2 specific ethico-legal concerns: (1) difficulty for health regulators; and (2) confusion about the assignment of liability for error or fault in the use of AI systems. We suggest that addressing these concerns is critical for ensuring AI's successful implementation in cardiovascular imaging.

Genetic counselors and legal recognition: A made-for-Canada approach.

Genetic counseling is a fast-growing profession in Canada. Yet, despite its growth, genetic counseling lacks legal recognition in the majority of Canadian provinces. Legal recognition serves to regulate professions, including genetic counseling, that if not properly regulated, expose the public to the risk of harm. Under Canadian law, there are three models of legal recognition: 1) the constitution of a professional order, 2) inclusion in a professional order, and 3) delegation. This paper explores the practical implications of these different models of legal recognition for genetic counselors. It focuses on the balancing act between protecting the public and the resources required to seek legal recognition under the three different models. With a small number of genetic counselors (n = 484, with 89% found in 4 provinces) compared to other professions, the route toward professional regulation for genetic counselors can be challenging. Though legal recognition occurs at the provincial rather than federal level in Canada, we nonetheless advocate for pan-Canadian discussions that may benefit future pursuits of legal recognition.

Should Age-Dependent Absolute Risk Thresholds Be Used for Risk Stratification in Risk-Stratified Breast Cancer Screening?

In risk-stratified cancer screening, multiple risk factors are incorporated into the risk assessment. An individual's estimated absolute cancer risk is linked to risk categories with tailored screening recommendations for each risk category. Absolute risk, expressed as either remaining lifetime risk or shorter-term (five- or ten-year) risk, is estimated from the age at assessment. These risk estimates vary by age; however, some clinical guidelines (e.g., enhanced breast cancer surveillance guidelines) and ongoing personalised breast screening trials, stratify women based on absolute risk thresholds that do not vary by age. We examine an alternative approach in which the risk thresholds used for risk stratification vary by age and consider the implications of using age-independent risk thresholds on risk stratification. We demonstrate that using an age-independent remaining lifetime risk threshold approach could identify high-risk younger women but would miss high-risk older women, whereas an age-independent 5-year or 10-year absolute risk threshold could miss high-risk younger women and classify lower-risk older women as high risk. With risk misclassification, women with an equivalent risk level would be offered a different screening plan. To mitigate these problems, age-dependent absolute risk thresholds should be used to inform risk stratification.