Background Acute myeloid leukemia (AML), a rapidly progressing cancer of the blood and bone marrow, is the most common and fatal type of adult leukemia. Therapeutic web portals have great potential to facilitate AML research advances and improve health outcomes by increasing the availability of data, the speed and reach of new knowledge, and the communication between researchers and clinicians in the field. However, there is a need for stakeholder research regarding their optimal features, utility, and implementation. Methods To better understand stakeholder perspectives regarding an ideal pan-Canadian web portal for AML research, semi-structured qualitative interviews were conducted with 17 clinicians, researchers, and clinician-researchers. Interview guides were inspired by De Laat’s “fictive scripting”, a method where experts are presented with scenarios about a future technology and asked questions about its implementation. Content analysis relied on an iterative process using themes extracted from both existing scientific literature and the data. Results Participants described potential benefits of an AML therapeutic portal including facilitating data-sharing, communication, and collaboration, and enhancing clinical trial matchmaking for patients, potentially based on their specific genomic profiles. There was enthusiasm about researcher, clinician, and clinician-researcher access, but some disagreement about the nature of potential patient access to the portal. Interviewees also discussed two key elements they believed to be vital to the uptake and thus success of a therapeutic AML web portal: credibility and user friendliness. Finally, sustainability, security and privacy concerns were also documented. Conclusions This research adds to existing calls for digital platforms for researchers and clinicians to supplement extant modes of communication to streamline research and its dissemination, advance precision medicine, and ultimately improve patient prognosis and care. Findings are applicable to therapeutic web portals more generally, particularly in genomic and translational medicine, and will be of interest to portal end-users, developers, researchers, and policymakers.

Background Artificial intelligence (AI)–based chatbots could help address some of the challenges patients face in acquiring information essential to their self-health management, including unreliable sources and overburdened health care professionals. Research to ensure the proper design, implementation, and uptake of chatbots is imperative. Inclusive digital health research and responsible AI integration into health care require active and sustained patient and stakeholder engagement, yet corresponding activities and guidance are limited for this purpose. Objective In response, this manuscript presents a master protocol for the development, testing, and implementation of a chatbot family in partnership with stakeholders. This protocol aims to help efficiently translate an initial chatbot intervention (MARVIN) to multiple health domains and populations. Methods The MARVIN chatbots study has an adaptive platform trial design consisting of multiple parallel individual chatbot substudies with four common objectives: (1) co-construct a tailored AI chatbot for a specific health care setting, (2) assess its usability with a small sample of participants, (3) measure implementation outcomes (usability, acceptability, appropriateness, adoption, and fidelity) within a large sample, and (4) evaluate the impact of patient and stakeholder partnerships on chatbot development. For objective 1, a needs assessment will be conducted within the setting, involving four 2-hour focus groups with 5 participants each. Then, a co-construction design committee will be formed with patient partners, health care professionals, and researchers who will participate in 6 workshops for chatbot development, testing, and improvement. For objective 2, a total of 30 participants will interact with the prototype for 3 weeks and assess its usability through a survey and 3 focus groups. Positive usability outcomes will lead to the initiation of objective 3, whereby the public will be able to access the chatbot for a 12-month real-world implementation study using web-based questionnaires to measure usability, acceptability, and appropriateness for 150 participants and meta-use data to inform adoption and fidelity. After each objective, for objective 4, focus groups will be conducted with the design committee to better understand their perspectives on the engagement process. Results From July 2022 to October 2023, this master protocol led to four substudies conducted at the McGill University Health Centre or the Centre hospitalier de l’Université de Montréal (both in Montreal, Quebec, Canada): (1) MARVIN for HIV (large-scale implementation expected in mid-2024), (2) MARVIN-Pharma for community pharmacists providing HIV care (usability study planned for mid-2024), (3) MARVINA for breast cancer, and (4) MARVIN-CHAMP for pediatric infectious conditions (both in preparation, with development to begin in early 2024). Conclusions This master protocol offers an approach to chatbot development in partnership with patients and health care professionals that includes a comprehensive assessment of implementation outcomes. It also contributes to best practice recommendations for patient and stakeholder engagement in digital health research. Trial Registration ClinicalTrials.gov NCT05789901; https://classic.clinicaltrials.gov/ct2/show/NCT05789901 International Registered Report Identifier (IRRID) PRR1-10.2196/54668

The role of genetic counselors is evolving in response to health-related direct-to-consumer genetic tests (DTC-GT). While there is consensus in the literature that pre- and post-DTC-GT genetic counseling would benefit consumers, genetic counselors have reservations about DTC-GTs, and there is a paucity of research on providing DTC-GT counseling. This pilot quantitative survey is the first study to examine Canadian genetic counselors’ views on DTC-GTs and how this disruptive biotechnology affects their role, and consumer informed consent and privacy. Canadian genetic counselors are cognizant of the harm to informed consent and privacy associated with DTC-GT, but are hesitant to engage directly, wary of misusing clinical time and resources. However, counselors are open to producing educational materials on DTC-GTs and collaborating with other stakeholders and the DTC-GT industry to support consumers. In this study, practical considerations for DTC-GT counseling sessions are discussed, including the unique needs of DTC-GT patients and the challenges posed by DTC-GTs to the genetic counseling duty to inform. This research benefits genetic counselors and physicians by examining how best to utilize genetic counselors’ skills in the DTC-GT context, to minimize burdens on the healthcare system and support DTC-GT consumers.

Abstract Scientific research communities pursue dual imperatives in implementing strategies to share their data. These communities attempt to maximize the accessibility of biomedical data for downstream research use, in furtherance of open science objectives. Simultaneously, such communities safeguard the interests of research participants through data stewardship measures and the integration of suitable risk disclosures to the informed consent process. The Canadian Open Neuroscience Platform (CONP) convened an Ethics and Governance Committee composed of experts in bioethics, neuroethics, and law to develop holistic policy tools, organizational approaches, and technological supports to align the open governance of data with ethical and legal norms. The CONP has adopted novel platform governance methods that favor full data openness, legitimated through the use of robust deidentification processes and informed consent practices. The experience of the CONP is articulated as a potential template for other open science efforts to further build upon. This experience highlights informed consent guidance, deidentification practices, ethicolegal metadata, platform-level norms, and commercialization and publication policies as the principal pillars of a practicable approach to the governance of open data. The governance approach adopted by the CONP stands as a viable model for the broader neuroscience and open science communities to adopt for sharing data in full open access.

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. Expected final online publication date for the Annual Review of Genomics and Human Genetics, Volume 24 is August 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

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.

Background: Sex and gender are vitally important in the study of epigenetic mechanisms for various types of cancer. However, little has been done to assess the state of sex and gender-based analyses (SGBA) in this field. The aim was to undertake a critical evaluation of sex and gender representation, discussion, and data analysis within the cancer epigenetics field since 2010. Methods: A PRISMA-ScR scoping review was conducted with 111 peer-reviewed studies comprising of colorectal, gastric, head and neck, hepatocellular carcinoma, and lung cancers. Data extraction and a quality appraisal were performed by a team of epidemiologists and bioethicists. Results: Of the 111 included studies, only 17 studies (15.3%) explicitly stated sex and gender analysis to be their primary aim. A total of 103 studies (92.8%) provided a detailed analysis of sex/gender as a biological or social variable, while the remaining 8 studies (7.2%) only stratified results by sex/gender. Although sex and gender were a key facet in all the eligible studies, only 7 studies (6.3%) provided an explicit definition of the terms “sex” or “gender”, while the remaining 104 studies (93.7%) used the words “sex” or “gender” without providing a definition. A total of 84 studies (75.7%) conflated the concepts of “sex” and “gender”, while 44 studies (39.6%) were inconsistent with their usage of the “sex” and “gender” terms. Conclusions: Very few studies offered a robust analysis of sex/gender data according to SAGER guidelines. We call for clear and directed guidelines regarding the use of sex/gender as a variable in epigenetics research.

Background: Sex and gender are vitally important in the study of epigenetic mechanisms for various types of cancer. However, little has been done to assess the state of sex and gender-based analyses (SGBA) in this field. The aim was to undertake a critical evaluation of sex and gender representation, discussion, and data analysis within the cancer epigenetics field since 2010. Methods: A PRISMA-ScR scoping review was conducted with 111 peer-reviewed studies comprising of colorectal, gastric, head and neck, hepatocellular carcinoma, and lung cancers. Data extraction and a quality appraisal were performed by a team of epidemiologists and bioethicists. Results: Of the 111 included studies, only 17 studies (15.3%) explicitly stated sex and gender analysis to be their primary aim. A total of 103 studies (92.8%) provided a detailed analysis of sex/gender as a biological or social variable, while the remaining 8 studies (7.2%) only stratified results by sex/gender. Although sex and gender were a key facet in all the eligible studies, only 7 studies (6.3%) provided an explicit definition of the terms “sex” or “gender”, while the remaining 104 studies (93.7%) used the words “sex” or “gender” without providing a definition. A total of 84 studies (75.7%) conflated the concepts of “sex” and “gender”, while 44 studies (39.6%) were inconsistent with their usage of the “sex” and “gender” terms. Conclusions: Very few studies offered a robust analysis of sex/gender data according to SAGER guidelines. We call for clear and directed guidelines regarding the use of sex/gender as a variable in epigenetics research.

Abstract Motivation Human epigenomic data has been generated by large consortia for thousands of cell types to be used as a reference map of normal and disease chromatin states. Since epigenetic data contains potentially identifiable information, similarly to genetic data, most raw files generated by these consortia are stored in controlled-access databases. It is important to protect identifiable information, but this should not hinder secure sharing of these valuable datasets. Results Guided by the Framework for responsible sharing of genomic and health-related data from the Global Alliance for Genomics and Health (GA4GH), we have developed a tool to facilitate the exploration of epigenomics datasets’ aggregate results, while filtering out identifiable information. Specifically, the EpiVar Browser allows a user to navigate an epigenetic dataset from a cohort of individuals and enables direct exploration of genotype-chromatin phenotype relationships. Because the information about individual genotypes is not accessible and aggregated in the output that is made available, no identifiable data is released, yet the interface allows for dynamic genotype - epigenome interrogation. This approach has the potential to accelerate analyses that would otherwise require a lengthy multi-step approval process and provides a generalisable strategy to facilitate responsible access to sensitive epigenomics data. Availability and implementation Online portal instance: https://computationalgenomics.ca/tools/epivar Source code: https://github.com/c3g/epivar-browser

The Canadian Open Neuroscience Platform (CONP) takes a multifaceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Its core infrastructure is the CONP Portal, a repository with a decentralized design, where datasets and analysis tools across disparate platforms can be browsed, searched, accessed, and shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server capable of creating and hosting executable and fully reproducible scientific publications that embed text, figures, and code. As part of its holistic approach, the CONP has also constructed frameworks and guidance for ethics and data governance, provided support and developed resources to help train the next generation of neuroscientists, and has fostered and grown an engaged community through outreach and communications. In this manuscript, we provide a high-level overview of this multipronged platform and its vision of lowering the barriers to the practice of open neuroscience and yielding the associated benefits for both individual researchers and the wider community.

Abstract Epigenetic research has brought several important technological achievements, including identifying epigenetic clocks and signatures, and developing epigenetic editing. The potential military applications of such technologies we discuss are stratifying soldiers’ health, exposure to trauma using epigenetic testing, information about biological clocks, confirming child soldiers’ minor status using epigenetic clocks, and inducing epigenetic modifications in soldiers. These uses could become a reality. This article presents a comprehensive literature review, and analysis by interdisciplinary experts of the scientific, legal, ethical, and societal issues surrounding epigenetics and the military. Notwithstanding the potential benefit from these applications, our findings indicate that the current lack of scientific validation for epigenetic technologies suggests a careful scientific review and the establishment of a robust governance framework before consideration for use in the military. In this article, we highlight general concerns about the application of epigenetic technologies in the military context, especially discrimination and data privacy issues if soldiers are used as research subjects. We also highlight the potential of epigenetic clocks to support child soldiers’ rights and ethical questions about using epigenetic engineering for soldiers’ enhancement and conclude with considerations for an ethical framework for epigenetic applications in the military, defense, and security contexts.

Abstract Risk prediction models hold great promise to reduce the impact of cancer in society through advanced warning of risk and improved preventative modalities. These models are evolving and becoming more complex, increasingly integrating genetic screening data and polygenic risk scores as well as calculating risk for multiple types of a disease. However, unclear regulatory compliance requirements applicable to these models raise significant legal uncertainty and new questions about the regulation of medical devices. This paper aims to address these novel regulatory questions by presenting an initial assessment of the legal status likely applicable to risk prediction models in Canada, using the CanRisk tool for breast and ovarian cancer as an exemplar. Legal analysis is supplemented with qualitative perspectives from expert stakeholders regarding the accessibility and compliance challenges of the Canadian regulatory framework. While the paper focuses on the Canadian context, it also refers to European and U.S. regulations in this domain to contrast them. Legal analysis and stakeholder perspectives highlight the need to clarify and update the Canadian regulatory framework for Software as a Medical Device as it applies to risk prediction models. Findings demonstrate how normative guidance perceived as convoluted, contradictory or overly burdensome can discourage innovation, compliance, and ultimately, implementation. This contribution aims to initiate discussion about a more optimal legal framework for risk prediction models as they continue to evolve and are increasingly integrated into landscape for public health.

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.

Abstract The coming-into-force of the EU General Data Protection Regulation (GDPR) is a watershed moment in the legal recognition of enforceable rights to informational self-determination. The rapid evolution of legal requirements applicable to data use, however, has the potential to outstrip the capabilities of networks of biomedical data users to respond to the shifting norms. It can also delegitimate established institutional bodies that are responsible for assessing and authorising the downstream use of data, including research ethics committees and institutional data custodians. These burdens are especially pronounced for clinical and research networks that are of transnational scale, because the legal compliance burden for outbound international data transfers from the EEA is especially high. Legislatures, courts, and regulators in the EU should therefore implement the following three legal changes. First, the responsibilities of particular actors in a data sharing network should be delimited through the contractual allocation of responsibilities between collaborators. Second, the use of data through secure data processing environments should not trigger the international transfer provisions of the GDPR. Third, the use of federated data analysis methodologies that do not provide analysis nodes or downstream users access to identifiable personal data as part of the outputs of those analyses should not be considered circumstances of joint controllership, nor lead to the users of non-identifiable data to be considered controllers or processors. These small clarifications of, or modifications to, the GDPR would facilitate the exchange of biomedical data amongst clinicians and researchers.

Background: The PREVENTION e-platform was developed to provide accessible and evidence-based health information tailored to different Breast Cancer (BC) risk levels. The demonstration study objectives were to (1) assess the usability and perceived impact of PREVENTION on women with assigned hypothetical BC risk levels (i.e., near population, intermediate or high) and (2) explore perceptions and recommendations for e-platform improvement. Methods: Thirty women with no history of cancer were recruited through social media, commercial centers, health clinics, and community settings in Montreal, Qc, Canada. Participants accessed e-platform content tailored to their assigned hypothetical BC risk level, and then completed study e-questionnaires including the user Mobile Application Rating Scale (uMARS), an e-platform quality scale (i.e., in terms of engagement, functionality, aesthetics, and information). A subsample (n = 18) was randomly selected for an individual follow-up semi-structured interview. Results: The e-platform overall quality was high, with mean M = 4.01 (out of 5) and SD = 0.50. A total of 87% (n = 26) agreed or strongly agreed that PREVENTION increased their knowledge and awareness of BC risk, and 80% would recommend it to others while reporting likelihood of following lifestyle recommendations to decrease their BC risk. Follow up interviews indicated that participants perceived the e-platform as a trusted source of BC information and a promising means to connect with peers. They also reported that while the e-platform was easy to navigate, improvements were needed for connectivity, visuals, and the organization of scientific resources. Conclusion: Preliminary findings support PREVENTION as a promising means to provide personalized BC information and support. Efforts are underway to further refine the platform, assess its impact in larger samples and gather feedback from BC specialists.

Abstract HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

Abstract HostSeq was launched in April 2020 as a national initiative to integrate whole genome sequencing data from 10,000 Canadians infected with SARS-CoV-2 with clinical information related to their disease experience. The mandate of HostSeq is to support the Canadian and international research communities in their efforts to understand the risk factors for disease and associated health outcomes and support the development of interventions such as vaccines and therapeutics. HostSeq is a collaboration among 13 independent epidemiological studies of SARS-CoV-2 across five provinces in Canada. Aggregated data collected by HostSeq are made available to the public through two data portals: a phenotype portal showing summaries of major variables and their distributions, and a variant search portal enabling queries in a genomic region. Individual-level data is available to the global research community for health research through a Data Access Agreement and Data Access Compliance Office approval. Here we provide an overview of the collective project design along with summary level information for HostSeq. We highlight several statistical considerations for researchers using the HostSeq platform regarding data aggregation, sampling mechanism, covariate adjustment, and X chromosome analysis. In addition to serving as a rich data source, the diversity of study designs, sample sizes, and research objectives among the participating studies provides unique opportunities for the research community.

• Disparities in COVID vaccination are in part due to ongoing impact of structural racism and neighborhood disinvestment. • Regional COVID vaccination disparities suggest a “one-size-fits-all” approach is insufficient to improve vaccine coverage. • Granular geographic data can identify targetable disparities and inform effective, equitable local public health approaches.

Objectives COVID-19 research has significantly contributed to pandemic response and the enhancement of public health capacity. COVID-19 data collected by provincial/territorial health authorities in Canada are valuable for research advancement yet not readily available to the public, including researchers. To inform developments in public health data-sharing in Canada, we explored Canadians’ opinions of public health authorities sharing deidentified individual-level COVID-19 data publicly. Design/setting/interventions/outcomes A national cross-sectional survey was administered in Canada in March 2022, assessing Canadians’ opinions on publicly sharing COVID-19 datatypes. Market research firm Léger was employed for recruitment and data collection. Participants Anyone greater than or equal to 18 years and currently living in Canada. Results 4981 participants completed the survey with a 92.3% response rate. 79.7% were supportive of provincial/territorial authorities publicly sharing deidentified COVID-19 data, while 20.3% were hesitant/averse/unsure. Datatypes most supported for being shared publicly were symptoms (83.0% in support), geographical region (82.6%) and COVID-19 vaccination status (81.7%). Datatypes with the most aversion were employment sector (27.4% averse), postal area (26.7%) and international travel history (19.7%). Generally supportive Canadians were characterised as being ≥50 years, with higher education, and being vaccinated against COVID-19 at least once. Vaccination status was the most influential predictor of data-sharing opinion, with respondents who were ever vaccinated being 4.20 times more likely (95% CI 3.21 to 5.48, p=0.000) to be generally supportive of data-sharing than those unvaccinated. Conclusions These findings suggest that the Canadian public is generally favourable to deidentified data-sharing. Identifying factors that are likely to improve attitudes towards data-sharing are useful to stakeholders involved in data-sharing initiatives, such as public health agencies, in informing the development of public health communication and data-sharing policies. As Canada progresses through the COVID-19 pandemic, and with limited testing and reporting of COVID-19 data, it is essential to improve deidentified data-sharing given the public’s general support for these efforts.

Health organisations use numerous different mechanisms to collect biomedical data, to determine the applicable ethical, legal and institutional conditions of use, and to reutilise the data in accordance with the relevant rules. These methods and mechanisms differ from one organisation to another, and involve considerable specialised human labour, including record-keeping functions and decision-making committees. In reutilising data at scale, however, organisations struggle to meet demands for data interoperability and for rapid inter-organisational data exchange due to reliance on legacy paper-based records and on the human-initiated administration of accompanying permissions in data. The adoption of permissions-recording, and permissions-administration tools that can be implemented at scale across numerous organisations is imperative. Further, these must be implemented in a manner that does not compromise the nuanced and contextual adjudicative processes of research ethics committees, data access committees, and biomedical research organisations. The tools required to implement a streamlined system of biomedical data exchange have in great part been developed. Indeed, there remains but a small core of functions that must further be standardised and automated to enable the recording and administration of permissions in biomedical research data with minimal human effort. Recording ethical provenance in this manner would enable biomedical data exchange to be performed at scale, in full respect of the ethical, legal, and institutional rules applicable to different datasets. This despite foundational differences between the distinct legal and normative frameworks is applicable to distinct communities and organisations that share data between one another.

Health organisations use numerous different mechanisms to collect biomedical data, to determine the applicable ethical, legal and institutional conditions of use, and to reutilise the data in accordance with the relevant rules. These methods and mechanisms differ from one organisation to another, and involve considerable specialised human labour, including record-keeping functions and decision-making committees. In reutilising data at scale, however, organisations struggle to meet demands for data interoperability and for rapid inter-organisational data exchange due to reliance on legacy paper-based records and on the human-initiated administration of accompanying permissions in data. The adoption of permissions-recording, and permissions-administration tools that can be implemented at scale across numerous organisations is imperative. Further, these must be implemented in a manner that does not compromise the nuanced and contextual adjudicative processes of research ethics committees, data access committees, and biomedical research organisations. The tools required to implement a streamlined system of biomedical data exchange have in great part been developed. Indeed, there remains but a small core of functions that must further be standardised and automated to enable the recording and administration of permissions in biomedical research data with minimal human effort. Recording ethical provenance in this manner would enable biomedical data exchange to be performed at scale, in full respect of the ethical, legal, and institutional rules applicable to different datasets. This despite foundational differences between the distinct legal and normative frameworks is applicable to distinct communities and organisations that share data between one another.

The use of smartphones has greatly increased in the last decade and has revolutionized the way that health data are being collected and shared. Mobile applications leverage the ubiquity and technological sophistication of modern smartphones to record and process a variety of metrics relevant to human health, including behavioral measures, clinical data, and disease symptoms. Information processed by mobile applications may have significant utility for increasing biomedical knowledge, both through conventional research and emerging discovery paradigms such as citizen science. However, the ways in which smartphone-collected data may be used in nontraditional modes of biomedical discovery are not well understood, such as using data to train artificially intelligent algorithms and for product development purposes. This paper argues that the use of mobile health data for algorithm training and product development is (a) likely to become a prominent fixture in medicine, (b) likely to raise significant ethical and legal challenges, and (c) warrants immediate scrutiny by policymakers and scholars. We introduce the concept of “smartphone-crowdsourced medical data,” or SCMD, and set out a broad research agenda for addressing concerns associated with this new and potentially momentous practice. We conclude that SCMD for algorithm training raises a number of ethical and legal issues which require further scholarly attention to ensure that individual interests are protected and that emerging health information sources can be used in ways that maximally, and safely, promote medical innovation.

Genetic counseling is a fast-growing profession worldwide, with genetic counselors taking on increasingly comprehensive and autonomous roles in the healthcare sector. However, the absence of appropriate legal frameworks could potentially create risks of harm to the public. Legal recognition serves to protect the public from risk of harm by regulating the safe and competent practice of healthcare professionals. Genetic counseling is not legally recognized in most world jurisdictions. Examination of the legal status of genetic counseling in different jurisdictions and whether existing legal mechanisms are adequate to address potential risks of harm is therefore timely. This paper examines the different roles of genetic counselors in the Canadian province of Quebec and the state of Qatar, the authors’ respective jurisdictions. It considers the types of harms that may be created where appropriate legal mechanisms are lacking, considering the socio-political and legal differences between the two jurisdictions. Moreover, it examines the legal status of genetic counseling in Quebec and Qatar to determine whether these statuses appropriately address the identified risks of harm. The authors argue that existing legal frameworks are inadequate to address these risks and recommend that additional regulatory mechanisms be implemented to properly protect the public from risks of harm.

Les ressources en ligne offrent un moyen particulièrement efficace de partager la recherche en santé avec les scientifiques et le public. L’utilisation de portails web pour mettre les résultats et les informations sur les études à la disposition de divers publics pourrait accélérer l’application des résultats de la recherche et permettre aux patients de jouer un rôle plus actif dans leurs soins. Cependant, l’utilisation d’outils en ligne pour partager largement des informations sur la santé soulève plusieurs questions éthiques et réglementaires délicates. Des questions telles que l’équité, la protection de la vie privée et l’autonomisation des patients peuvent poser des problèmes aux organismes de réglementation, aux concepteurs de portails et aux chercheurs. En outre, il n’est pas certain que les portails web conçus pour faciliter l’accès aux résultats de la recherche et aux informations générales sur la santé soient réglementés en tant que dispositifs médicaux dans le cadre des régimes émergents qui contrôlent les logiciels à des fins médicales. Le présent document a pour but d’examiner de manière comparative si les portails thérapeutiques en ligne destinés au partage de la recherche en matière de santé sont susceptibles d’être réglementés au Canada, aux États-Unis, au Royaume-Uni et en France. Nous constatons que, bien que ces juridictions aient toutes pris des mesures récentes pour réglementer les logiciels en tant que dispositifs médicaux, les régimes applicables n’englobent généralement pas les portails en ligne destinés au partage de la recherche en matière de santé. Bien que les portails en ligne pour le partage de la recherche en santé ne soient probablement pas réglementés dans de nombreuses juridictions (si ce n’est la plupart), les agences ont néanmoins fait part de leurs préoccupations concernant plusieurs considérations éthiques importantes (telles que l’équité, la transparence et la sécurité), auxquelles les développeurs de portails et les chercheurs doivent être attentifs et répondre. Nous décrivons ici un ensemble de questions soulignées par les régulateurs – à savoir l’efficacité, l’équité, la transparence, la confidentialité, la communication, la responsabilisation, la formation, la sécurité et l’efficacité – et examinons comment guider au mieux la conception des portails en ligne dans un contexte d’incertitude réglementaire.

Knowledge transfer among research disciplines can lead to substantial research progress. At first glance, astronaut health and rare diseases may be seen as having little common ground for such an exchange. However, deleterious health conditions linked to human space exploration may well be considered as a narrow sub-category of rare diseases. Here, we compare and contrast research and healthcare in the contexts of rare diseases and space health and identify common barriers and avenues of improvement. The prevalent genetic basis of most rare disorders contrasts sharply with the occupational considerations required to sustain human health in space. Nevertheless small sample sizes and large knowledge gaps in natural history are examples of the parallel challenges for research and clinical care in the context of both rare diseases and space health. The two areas also face the simultaneous challenges of evidence scarcity and the pressure to deliver therapeutic solutions, mandating expeditious translation of research knowledge into clinical care. Sharing best practices between these fields, including increasing participant involvement in all stages of research and ethical sharing of standardized data, has the potential to contribute to humankind’s efforts to explore ever further into space while caring for people on Earth in a more inclusive fashion.

Background Breast cancer risk stratification categorizes a woman’s potential risk of developing the disease as near-population, intermediate, or high. In accordance, screening and follow up for breast cancer can readily be tailored following risk assessment. Recent efforts have focussed on developing more accessible means to convey this information to women. This study sought to document the relevance of an informational e-platform developed for these purposes. Objective To begin to assess a newly developed breast cancer risk stratification and decision support e-platform called PERSPECTIVE (PErsonalised Risk Stratification for Prevention and Early deteCTIon of breast cancer) among women who do not know their personal breast cancer risk (Phase 1). Changes (pre- and post- e-platform exposure) in knowledge of breast cancer risk and interest in undergoing genetic testing were assessed in addition to perceptions of platform usability and acceptability. Methods Using a pre-post design, women (N= 156) of differing literacy and education levels, aged 30 to 60, with no previous breast cancer diagnosis were recruited from the general population and completed self-report e-questionnaires. Results Mean e-platform viewing time was 18.67 min (SD 0.65) with the most frequently visited pages being breast cancer-related risk factors and risk assessment. Post-exposure, participants reported  significantly higher breast cancer-related knowledge (p< .001). Increases in knowledge relating to obesity, alcohol, breast density, menstruation, and the risk estimation process remained even when sociodemographic variables age and education were controlled. There were no significant changes in genetic testing interest post-exposure. Mean ratings for e-platform acceptability and usability were high: 26.19 out of 30 (SD 0.157) and 42.85 out of 50 (SD 0.267), respectively. Conclusions An informative breast cancer risk stratification e-platform targeting healthy women in the general population can significantly increase knowledge as well as support decisions around breast cancer risk and assessment. Currently underway, Phase 2, called PERSPECTIVE, is seeking further content integration and broader implementation .

Abstract Background The Coronavirus Disease-2019 (COVID-19) pandemic has created a spectrum of adversities that have affected older adults disproportionately. This paper examines older adults with multimorbidity using longitudinal data to ascertain why some of these vulnerable individuals coped with pandemic-induced risk and stressors better than others – termed multimorbidity resilience. We investigate pre-pandemic levels of functional, social and psychological forms of resilience among this sub-population of at-risk individuals on two outcomes – self-reported comprehensive pandemic impact and personal worry. Methods This study was conducted using Follow-up 1 data from the Canadian Longitudinal Study on Aging (CLSA), and the Baseline and Exit COVID-19 study, conducted between April and December in 2020. A final sub-group of 9211 older adults with two or more chronic health conditions were selected for analyses. Logistic regression and Generalized Linear Mixed Models were employed to test hypotheses between a multimorbidity resilience index and its three sub-indices measured using pre-pandemic Follow-up 1 data and the outcomes, including covariates. Results The multimorbidity resilience index was inversely associated with pandemic comprehensive impact at both COVID-19 Baseline wave (OR = 0.83, p  < 0.001, 95% CI: [0.80,0.86]), and Exit wave (OR = 0.84, p  < 0.001, 95% CI: [0.81,0.87]); and for personal worry at Exit (OR = 0.89, p < 0.001, 95% CI: [0.86,0.93]), in the final models with all covariates. The full index was also associated with comprehensive impact between the COVID waves (estimate = − 0.19, p  < 0.001, 95% CI: [− 0.22, − 0.16]). Only the psychological resilience sub-index was inversely associated with comprehensive impact at both Baseline (OR = 0.89, p  < 0.001, 95% CI: [0.87,0.91]) and Exit waves (OR = 0.89, p < 0.001, 95% CI: [0.87,0.91]), in the final model; and between these COVID waves (estimate = − 0.11, p < 0.001, 95% CI: [− 0.13, − 0.10]). The social resilience sub-index exhibited a weak positive association (OR = 1.04, p  < 0.05, 95% CI: [1.01,1.07]) with personal worry, and the functional resilience measure was not associated with either outcome. Conclusions The findings show that psychological resilience is most pronounced in protecting against pandemic comprehensive impact and personal worry. In addition, several covariates were also associated with the outcomes. The findings are discussed in terms of developing or retrofitting innovative approaches to proactive coping among multimorbid older adults during both pre-pandemic and peri-pandemic periods.

This first report of the Forensic Databases Advisory Board (FDAB) aims to provide the International Society for Forensic Genetics (ISFG) with a framework to assess the ethical implications of hosting data from a variety of population groups on the forensic genetic frequency databases (FGFD) known as Y-chromosome Haplotype Reference Database (YHRD), the EDNAP Mitochondrial DNA Population Database (EMPOP) and the STRs for Identity ENFSI Reference Database (STRidER).These free FGFD were developed to serve as statistical support to the evaluation of forensic evidence (match, kinship) which benefits the advancement of science and society in general. Ethical considerations in this report include questions of data acquisition, data sensitivity and identifiability and ethical principles to be implemented. Submissions to the FGFD were classified with consideration to evolving ethical landmarks including those applicable to biomedical research, namely the Declaration of Helsinki (1975), the UNESCO Universal Declaration on the Human Genome and Human Rights (1997), as well as more specific Forensic Science International: Genetics (FSIG) guidelines published in 2010 and 2020. Further classification of data was defined by its source (academic, law enforcement, private, etc.). However, the complexity of the composition, variety of submissions and evolving ethics regulations pertinent to these FGFD rendered the composition of an appropriate ethical assessment framework challenging. It was therefore found that notwithstanding considerations proposed to the ISFG for an appropriate assessment of data held on the FGFD, a deeper debate is required on the role and acceptable alternatives to informed consent, the impact of including datasets on minorities and vulnerable groups, and other relevant ethical aspects for a complete risk-benefit assessment of data hosted on the FGFD.

Over the past two decades, we have seen unprecedented advancements in genomics, DNA sequencing technologies, and bioinformatics. Generating and assembling human genomic sequences has become faster, easier, and cheaper. Greater access to these large amounts of OMICS data should, in turn, improve screening programs and tests, personalized medicine, and forensic investigations.1,2,3

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.

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.

Abstract Objectives Studies on informal caregiving during the coronavirus disease 2019 (COVID-19) pandemic have mainly focused on subgroups of caregivers using cross-sectional or convenience samples, limiting the generalizability of findings. Conversely, this longitudinal study examines the effects of the pandemic and caregiving factors on depressive symptoms and anxiety over 9 months among informal caregivers in Canada. Methods This study uses data from the Baseline (2011–2015), Follow-up 1 (2015–2018), and COVID-19 Study Baseline survey (April to May 2020) and Exit surveys (September to December 2020) of the Canadian Longitudinal Study on Aging (CLSA). A total of 14,118 CLSA participants who were caregivers at Follow-up 1 and participated in the COVID-19 studies were selected. Linear mixed models were used to examine the effect of sex of caregiver, changes in caregiving (increase in caregiving hours and inability to care), and location of care (same household, another household, and health care institution) on depressive symptoms and anxiety from COVID-19 studies Baseline to Exit surveys (about 6–7 months apart). Results Informal caregivers reported more frequent depressive symptoms from the COVID-19 Baseline to Exit surveys, but not anxiety. Female caregivers reported greater depressive symptoms and anxiety, and male caregivers exhibited a greater increase in depressive symptoms and anxiety over time. More caregiving hours and inability to provide care were significantly positively associated with depressive symptoms and anxiety. Also, in-home caregivers reported more depressive symptoms and anxiety than those who cared for someone in health care institution, and more anxiety than those who cared for some in another household. Discussion The findings shed light on the change in mental health among informal caregivers during the outset of the pandemic. The demonstrated associations between studied variables and mental health among informal caregivers provide empirical evidence for intervention programs aiming to support caregivers, particularly those who are female, and providing intensive care at home.

Participants in the human gene editing debate often consider examples from science fiction but have rarely engaged directly with the science fiction community as stakeholders. To understand how science fiction authors develop and spread their views on gene editing, we created an online questionnaire that was answered by 78 authors, including 71 who had previously written about genetic engineering. When asked which ethical issues science fiction should explore, respondents most frequently mentioned affordability, new social divisions, consent and unforeseen safety risks. They rarely advocated exploring psychological effects or religious objections. When asked which works of fiction had influenced their perceptions of gene editing, the most frequent responses were the film Gattaca, the Star Trek franchise and the novels The Island of Doctor Moreau and Brave New World Unlike other stakeholders, they rarely cited Frankenstein as an influence. This article examines several differences between bioethicists, the general public and science fiction authors, and discusses how this community's involvement might benefit proponents and opponents of gene editing. It also provides an overview of works mentioned by our respondents that might serve as useful references in the debate.

Health professionals not specialized in genetics are expected to take an increasing role in genetic services delivery. This article aims to identify legal and ethical challenges related to a collaborative oncogenetics service model, where non-genetic health professionals provide genetic services to patients. Through a scoping literature review, we identified issues to the provision of hereditary breast and ovarian cancer, or other hereditary adult cancers, genetic testing under this model. Concerns that arose in the literature were informed consent, lack of adherence to best practice guidelines, lack of education of non-genetic health professionals on the provision of genetic services, psychological impacts of genetic testing, continuity of care, the complexity of genetic test results, confidentiality, risks of medical mismanagement, and the associated medical responsibility liabilities. Despite these challenges, there is a growing consensus towards the feasibility of cancer genetic testing being undertaken by non-genetic healthcare professionals in a collaborative oncogenetics service model.

Population-based newborn screening (NBS) is among the most effective public health programs ever launched, improving health outcomes for newborns who screen positive worldwide through early detection and clinical intervention for genetic disorders discovered in the earliest hours of life. Key to the success of newborn screening programs has been near universal accessibility and participation. Interest has been building to expand newborn screening programs to also include many rare genetic diseases that can now be identified by exome or genome sequencing (ES/GS). Significant declines in sequencing costs as well as improvements to sequencing technologies have enabled researchers to elucidate novel gene-disease associations that motivate possible expansion of newborn screening programs. In this paper we consider recommendations from professional genetic societies in Europe and North America in light of scientific advances in ES/GS and our current understanding of the limitations of ES/GS approaches in the NBS context. We invoke the principle of proportionality—that benefits clearly outweigh associated risks—and the human right to benefit from science to argue that rigorous evidence is still needed for ES/GS that demonstrates clinical utility, accurate genomic variant interpretation, cost effectiveness and universal accessibility of testing and necessary follow-up care and treatment. Confirmatory or second-tier testing using ES/GS may be appropriate as an adjunct to conventional newborn screening in some circumstances. Such cases could serve as important testbeds from which to gather data on relevant programmatic barriers and facilitators to wider ES/GS implementation.

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.

Abstract Identifying persons who are least willing to receive a coronavirus disease 2019 (COVID-19) vaccine is critical for increasing uptake via targeted outreach. We conducted a survey of 23,819 Canadian Longitudinal Study on Aging participants from September 29 to December 29, 2020, to assess factors associated with COVID-19 vaccination willingness and reasons for willingness or lack thereof. Among adults aged 50–96 years, 84.1% (95% confidence interval (CI): 83.7, 84.6) were very or somewhat willing to receive a COVID-19 vaccine; 15.9% (95% CI: 15.4, 16.3) were uncertain or very or somewhat unwilling. Based on logistic regression, those who were younger, female, had lower education and income, were non-White, and lived in a rural area were less willing to receive a COVID-19 vaccine. After controlling for these factors, recent receipt of influenza vaccine (adjusted odds ratio = 14.3, 95% CI: 12.5, 16.2) or planning to receive influenza vaccine (adjusted odds ratio = 10.5, 95% CI: 9.5, 11.6), as compared with no receipt or planning, was most strongly associated with COVID-19 vaccination willingness. Willingness was also associated with believing one had never been infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) and experiencing negative pandemic consequences. Safety concerns were most common among those unwilling. Our comprehensive assessment of COVID-19 vaccination willingness among older adults in Canada, a prioritized group for vaccination due to their risk of severe COVID-19 outcomes, provides a road map for conducting outreach to increase uptake, which is urgently needed.

A world-class health data system requires a strong foundation. This foundation supports the collection, access, sharing and use of health data in a timely and trusted manner for the benefit of all persons in Canada. The last two years of the COVID-19 pandemic have demonstrated the value of a strong foundation – common standards, functions, and capabilities – to inform public health advice, deliver health services, advance research and foster virtual care. Sadly, the pandemic has also shone a light on long-standing problems that weaken the foundation: the systemic fragmentation of health data, ineffective pan-Canadian health data governance and antiquated policies that have prevented timely data sharing . Had a stronger health data foundation been in place, health inequities experienced during the pandemic would have been reduced and lives would have been saved. Strengthening the health data foundation will require collaboration and considered effort toward a common goal. That common goal should be to establish a learning health system in Canada. In a learning health system, connected data support insights that drive evidence-informed decisions. These data and insights are embedded in health programs, services, surveillance programs and care delivery. When harnessed effectively, they can produce continual improvement and better and equitable outcomes for all.

This paper summarizes the results of a 31-country qualitative study of expert perspectives on the regulation of international “direct-to-participant” (DTP) genomic research. We outline how the practice of directly recruiting participants for genomic studies online complicates ethics and regulatory considerations for the return of individual research results. As part of a larger project supported by the National Human Genome Research Institute, National Institutes of Health, we prepared and distributed to 31 global legal experts a questionnaire intended to ascertain opinions and perspectives on the way international DTP genomic research is likely to be regulated. We found significant disagreement across jurisdictions on the most favorable approach to managing such results, with some countries favoring return by default and others preferring to return only with the express consent of research participants. We conclude by outlining policy considerations that should guide researcher practices in this context. As international DTP genomic research evolves, jurists and ethicists should be attentive to the ways novel approaches to subject recruitment align with existing ethical and regulatory norms in research with human participants. This paper is a preliminary step toward documenting such alignment in the context of the return of individual research results.

COVID-19 was declared to be a pandemic in March 2020 by the World Health Organization. Timely sharing of viral genomic sequencing data accompanied by a minimal set of contextual data is essential for informing regional, national, and international public health responses. Such contextual data is also necessary for developing, and improving clinical therapies and vaccines, and enhancing the scientific community’s understanding of the SARS-CoV-2 virus. The Canadian COVID-19 Genomics Network (CanCOGeN) was launched in April 2020 to coordinate and upscale existing genomics-based COVID-19 research and surveillance efforts. CanCOGeN is performing large-scale sequencing of both the genomes of SARS-CoV-2 virus samples (VirusSeq) and affected Canadians (HostSeq). This paper addresses the privacy concerns associated with sharing the viral sequence data with a pre-defined set of contextual data describing the sample source and case attribute of the sequence data in the Canadian context. Currently, the viral genome sequences are shared by provincial public health laboratories and their healthcare and academic partners, with the Canadian National Microbiology Laboratory and with publicly accessible databases. However, data sharing delays and the provision of incomplete contextual data often occur because publicly releasing such data triggers privacy and data governance concerns. The CanCOGeN Ethics and Governance Expert Working Group thus has investigated several privacy issues cited by CanCOGeN data providers/stewards. This paper addresses these privacy concerns and offers insights primarily in the Canadian context, although similar privacy considerations also exist in other jurisdictions. We maintain that sharing viral sequencing data and its limited associated contextual data in the public domain generally does not pose insurmountable privacy challenges. However, privacy risks associated with reidentification should be actively monitored due to advancements in reidentification methods and the evolving pandemic landscape. We also argue that during a global health emergency such as COVID-19, privacy should not be used as a blanket measure to prevent such genomic data sharing due to the significant benefits it provides towards public health responses and ongoing research activities.

Currently, most advances in site-specific epigenetic editing for human use are concentrated in basic research, yet, there is considerable interest to translate this technology beyond the bench. This review highlights recent developments with epigenetic editing technology in comparison with the canonical CRISPR-Cas genome editing, as well as the epistemic and ethical considerations with preemptive translation of epigenetic editing into clinical or commercial use in humans. Key considerations in safety, equity, and access to epigenetic editing are highlighted, with a spotlight on the ethical, legal, and social issues of this technology in the context of global health equity.

Single-site review means protection and efficiency

Despite recent progress in the understanding of the genetic etiologies of rare diseases (RDs), a significant number remain intractable to diagnostic and discovery efforts. Broad data collection and sharing of information among RD researchers is therefore critical. In 2018, the Care4Rare Canada Consortium launched the project C4R-SOLVE, a subaim of which was to collect, harmonize, and share both retrospective and prospective Canadian clinical and multiomic data. Here, we introduce Genomics4RD, an integrated web-accessible platform to share Canadian phenotypic and multiomic data between researchers, both within Canada and internationally, for the purpose of discovering the mechanisms that cause RDs. Genomics4RD has been designed to standardize data collection and processing, and to help users systematically collect, prioritize, and visualize participant information. Data storage, authorization, and access procedures have been developed in collaboration with policy experts and stakeholders to ensure the trusted and secure access of data by external researchers. The breadth and standardization of data offered by Genomics4RD allows researchers to compare candidate disease genes and variants between participants (i.e., matchmaking) for discovery purposes, while facilitating the development of computational approaches for multiomic data analyses and enabling clinical translation efforts for new genetic technologies in the future.

Large-scale data-centric challenges faced by neuroscientists, such as improving reproducibility and data reuse, could be overcome by adopting open science practises. The Canadian Open Neuroscience Platform (CONP) takes a multi-faceted approach to enabling open neuroscience, aiming to make research, data, and tools accessible to everyone, with the ultimate objective of accelerating discovery. Central to the tailor-made CONP infrastructure is its Portal, where datasets and analysis tools can be shared in accordance with FAIR principles. Another key piece of CONP infrastructure is NeuroLibre, a preprint server for interactive, fully reproducible scientific notebooks that embed text, figures, and code. To encourage responsible sharing, the CONP has constructed governance frameworks and toolkits that strike a balance between safeguarding the rights of data subjects and promoting widespread public benefit from scientific advancement. The CONP is also focussed on supporting the next generation of neuroscientists through its scholar and training program. The collective experience of our engaged community and leaders has generated a platform that supports multiple facets of open neuroscience, a unique approach within the neuroscience landscape. Together, the various elements of the platform serve the CONP’s vision for promoting open neuroscience and yielding the associated benefits for individual researchers and the wider community.

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.

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.

Abstract 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.

Abstract 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.

Purpose Matchmaking has emerged as a useful strategy for building evidence toward causality of novel disease genes in patients with undiagnosed rare diseases. The Matchmaker Exchange (MME) is a collaborative initiative that facilitates international data sharing for matchmaking purposes; however, data on user experience is limited. Methods Patients enrolled as part of the Finding of Rare Disease Genes in Canada (FORGE) and Care4Rare Canada research programs had their exome sequencing data reanalyzed by a multidisciplinary research team over a 2-year period. Compelling variants in genes not previously associated with a human phenotype were submitted through the MME node PhenomeCentral, and outcomes were collected. Results In this study, 194 novel candidate genes were submitted to the MME, resulting in 1514 matches, and 15% of the genes submitted resulted in collaborations. Most submissions resulted in at least 1 match, and most matches were with GeneMatcher (82%), where additional email exchange was required to evaluate the match because of the lack of phenotypic or inheritance information. Conclusion Matchmaking through the MME is an effective way to investigate novel candidate genes; however, it is a labor-intensive process. Engagement from the community to contribute phenotypic, genotypic, and inheritance data will ensure that matchmaking continues to be a useful approach in the future.

Re-contacting minors enrolled in research upon their reaching the age of majority or maturity to seek their autonomous consent to continue their participation is considered an ethical requirement. This issue has generally been studied in the context of minors who are actively involved in the research. However, what becomes of this issue when the minor has been withdrawn from the research or has been lost to follow-up? May researchers re-contact the minor at the age of majority or maturity under these circumstances to seek the consent of the minor to re-join the research? In this paper, we explore the ethical permissibility of recontacting minors whose participation in research has ended, once they have reached the age of majority or maturity. In particular, we identify scenarios in which the participation of a minor in a research project may end and discuss factors that can help determine such an ethical permissibility. Finally, we discuss the practical and ethical challenges of re-contact and present re-consent models that may be used by researchers. Keywords: re-contact, re-consent, minors, consent, assent, research, ethics

Epigenetics – the study of mechanisms that influence and modify gene expression – is providing unique insights into how an individual’s social and physical environment impact the body at a molecular level, particularly in populations that experience stigmatization and trauma. Researchers are employing epigenetic studies to illuminate how epigenetic modifications lead to imbalances in health outcomes for vulnerable populations. However, the investigation of factors that render a population epigenetically vulnerable present particular ethical and methodological challenges. Here we are concerned with demonstrating how, in targeting certain populations for epigenetic research, this research may be pathologizing socio-cultural and medical practices in those populations in a way that increases their vulnerability. Using a case study approach, this article examines three vulnerable populations currently of interest to epigenetic researchers – Indigenous, autistic, and transgender populations – in order to highlight some of the challenges of conducting non-stigmatizing research in epigenetics. Keywords: epigenetics, research ethics, c onfidentiality, privacy, social science research, vulnerable populations

IntroductionMaking 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.MethodsA 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.ResultsOverall, 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.ConclusionStudy 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.

The Human Cell Atlas (HCA) is a global partnership of scientists who are seeking to understand how the cells in our bodies work together to form our organs and carry out specific physiological functions essential to life. HCA scientists are creating a view of healthy cells and their behaviours in individuals, representing a diverse set of people to help better understand human biology, as well as the contributions of our environments and genetics to the ways in which our cells work to keep us well. Recognizing that many medical breakthroughs have not been beneficial to all because healthcare research has often been conducted without considering the impacts of variations in our genetic make-up, environmental exposures or life-experiences. Some previous scientific studies have been extractive and exploitative, failing to sufficiently consider the priorities of, or benefits to, contributing communities. In this narrative, HCA provides a set of principles and action items that have been adopted to affirm its commitment to promote equity so that the results of this global scientific endeavour are beneficial to all of humanity.

Les personnes présentant des variations intersexuelles se Individuals with intersex variations fall outside the normative sex situent en dehors du binaire sexuel normatif homme/femme binary of male and female for various reasons. These individuals pour diverses raisons. Ces personnes sont fortement are highly stigmatized and discriminated against in the legal, stigmatisées et discriminées dans les sphères juridiques, medical and social spheres. In this paper, we analyze médicale et sociale. Dans cet article, nous analysons les manifestations of such discrimination in the healthcare context manifestations de cette discrimination dans le contexte des and hypothesize that Patient Centred Care (PCC) and Shared soins de santé et nous émettons l’hypothèse que les approches Decision Making (SDM) approaches are improperly practiced de soins centrés sur le patient (SCP) et de prise de décision with intersex individuals. Through a narrative review of current partagée (PDP) sont mal pratiquées avec les personnes literature, we present evidence of improper practice of PCC and intersexuées. Un examen narratif de la littérature actuelle SDM and its effects on intersex individuals and, in the pediatric permet de présenter les preuves d’une pratique inadéquate des context, their parents. Misinformation by medical practitioners to SCP et de la PDP, ainsi que leurs répercussions sur les parents of intersex individuals promotes the perpetuation of personnes intersexuées et, dans le contexte pédiatrique, sur unnecessary surgical interventions. We propose strategies to leurs parents. La désinformation des parents de personnes improve intersex medical care, including better adherence to intersexuées par les praticiens médicaux favorise la SDM and PCC guidelines as well as the sociocultural perpétuation d’interventions chirurgicales inutiles. Nous normalisation of intersex identity. Current perceptions of surgical proposons des stratégies pour améliorer les soins médicaux aux interventions done on intersex infants and children need to personnes intersexuées, notamment une meilleure adhésion better align with evidence-based physical and psychological aux directives de la SCP et du PDP ainsi que la normalisation health risks. All these strategies are part of preserving the socioculturelle de l’identité intersexuée. Les perceptions autonomy and physical integrity of intersex individuals and actuelles des interventions chirurgicales pratiquées sur les ensuring that their well-being remains at the heart of their care nourrissons et les enfants intersexués doivent mieux in the medical context.

Over the past potential implications of epigenetic research and technologies on medicine and society. There is growing literature discussing the most promising opportunities, as well as arising ethical, legal and social issues (ELSI). This paper explores the views of epigenetic researchers about some of these discussions. From January to March 2020, we conducted an online survey of 189 epigenetic researchers working in 31 countries. We questioned them about the scope of their field, opportunities in different areas of specialization, and ELSI in the conduct of research and knowledge translation. We also assessed their level of concern regarding four emerging non-medical applications of epigenetic testing—i.e., in life insurance, forensics, immigration and direct-to-consumer testing. Although there was strong agreement on DNA methylation, histone modifications, 3D structure of chromatin and nucleosomes being integral elements of the field, there was considerable disagreement on transcription factors, RNA interference, RNA splicing and prions. The most prevalent ELSI experienced or witnessed by respondents were in obtaining timely access to epigenetic data in existing databases, and in the communication of epigenetic findings by the media. They expressed high levels of concern regarding non-medical applications of epigenetics, echoing cautionary appraisals in the social sciences and humanities literature.

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.

When writing about deliberate changes to the human germline, bioethicists tend not to discuss the modification of specific genes and instead refer to broader concepts like making people smarter, taller, or longer-lived. Only a limited number of these traits are mentioned regularly in the literature. Examples like health and intelligence appear frequently at all stages of the germline modification discourse, but the third most frequently mentioned trait has shifted over time. Prior to the early 1980s, publications discussed giving humans a kinder temperament significantly more often than cosmetic modifications, while more recent works reverse the frequency of these traits. Contributing factors likely include a greater focus on individual decision-making, combined with the increasing uptake of real-world reproductive technologies like IVF and gamete donation. This shifting imagery could have a profound influence on the way scholars develop arguments about gene editing since cosmetic modifications are generally viewed more negatively and considered less relevant to the identity of future people. In comparison with earlier images of germline modification, they also suggest a more contemporary, Western, and politically liberal social context for gene editing technology. Examining how authors move between writing about different traits can also help us to be aware of the traits that are arbitrarily omitted from the discourse and to consider our preparedness for unexpected kinds of modification.

This paper presents an inter-disciplinary study of the risk for, and protections against, genetic discrimination in access to life insurance in Ukraine. It aims (i) to review questions related to genetic information, health status, and family history currently included in Ukrainian life insurance application forms; (ii) to analyze the Ukrainian legislation related to equity and nondiscrimination and to determine whether it provides adequate protection against genetic discrimination (GD). Research findings of our insurance application forms review show that Ukrainian life insurance companies ask broad questions about health and family history that may be perceived by applicants as requiring the disclosure of their genetic information. Our legal analysis shows that today there are no genetic specific law protecting Ukrainians people against GD in insurance. However, Ukrainian human rights legislation provides some protection against multiple grounds of discrimination and given the ratification by Ukraine of the European Convention on Human Rights it is possible that these grounds could be interpreted by tribunals as also including genetic characteristics. As a next step, Ukrainian researchers should develop a survey to obtain much needed data on the incidence and impact of GD in Ukraine. Following this it will be possible for policymakers to better assess whether there is a need for an explicit non-GD law in this country. Such a law would have the benefit of explicitly aligning Ukraine’s legal framework with that of many of its European partners.

Macro events like the Great Depression in the 1930s and the Second World War have triggered new departures in social policy. What about the COVID-19 pandemic and the attendant socio-economic crisis? This article analyses the social protection measures taken by governments in the global South in response to the crisis, the social protection concepts developed by international organisations, and the overall strategies of the organisations in view of future shocks. The finding is that while the measures taken by governments expectedly have just been stopgap measures of a transitory nature, international organisations are aspiring to future-oriented policies and present a range of concepts for the time after the crisis. However, these are old concepts from pre-COVID-19 times, and the main strategy is to expand rather than reform the old models, even though the international organisations themselves identify new forms of poverty and structural inequalities. Moreover, the organisations do not provide conclusive evidence of their strategy’s viability; the strategy rather reflects a belief in social progress. All in all, the crisis has hardly been used as a window of opportunity for generating new ideas of social protection. Rather, the crisis has revealed the flimsy nature of widespread thinking about building social protection in the global South. Conceptually, the article draws on world society theory, conceiving of the pandemic as a global macro event.

Graeme Laurie’s notion of reflexive governance, rooted in learning from experiences as issues arise, reminds us that the future is built upon past lessons. This chapter looks to the past better to understand our present and future. It begins with the past, examining the complex interaction of law, ethics and science through the prism of three types of human rights: the rights of children and decisionally vulnerable adults, the right to benefit from scientific advancement, and the rights of future generations. It traces the maturation of each from humble beginnings to playing an increasingly central role in biomedical research policy-making. It then turns to the future, largely uncertain but nevertheless responding to the past and the present. It contends that the future of policy-making is partly in the debates spurred by advances in epigenomics and microbiomics, human heritable genome editing, and the Covid-19 pandemic. Each has put our policy-making legacy to the test, illustrating how new ethical paradigms build upon older ones. It concludes by reflecting on the role that biomedical research policy plays in ensuring that science serves the interests of humanity above all else.

Policies shape society. Public health policies are of particular importance, as they often dictate matters in life and death. Accumulating evidence indicates that good-intentioned COVID-19 policies, such as shelter-in-place measures, can often result in unintended consequences among vulnerable populations such as nursing home residents and domestic violence victims. Thus, to shed light on the issue, this study aimed to identify policy-making processes that have the potential of developing policies that could induce optimal desirable outcomes with limited to no unintended consequences amid the pandemic and beyond. Methods: A literature review was conducted in PubMed, PsycINFO, and Scopus to answer the research question. To better structure the review and the subsequent analysis, theoretical frameworks such as the social ecological model were adopted to guide the process. Results: The findings suggested that: (1) people-centered; (2) artificial intelligence (AI)-powered; (3) data-driven, and (4) supervision-enhanced policy-making processes could help society develop policies that have the potential to yield desirable outcomes with limited unintended consequences. To leverage these strategies’ interconnectedness, the people-centered, AI-powered, data-driven, and supervision-enhanced (PADS) model of policy making was subsequently developed. Conclusions: The PADS model can develop policies that have the potential to induce optimal outcomes and limit or eliminate unintended consequences amid COVID-19 and beyond. Rather than serving as a definitive answer to problematic COVID-19 policy-making practices, the PADS model could be best understood as one of many promising frameworks that could bring the pandemic policy-making process more in line with the interests of societies at large; in other words, more cost-effectively, and consistently anti-COVID and pro-human.

Various data sharing platforms are being developed to enhance the sharing of cohort data by addressing the fragmented state of data storage and access systems. However, policy challenges in several domains remain unresolved. The euCanSHare workshop was organized to identify and discuss these challenges and to set the future research agenda. Concerns over the multiplicity and long-term sustainability of platforms, lack of resources, access of commercial parties to medical data, credit and recognition mechanisms in academia and the organization of data access committees are outlined. Within these areas, solutions need to be devised to ensure an optimal functioning of platforms.

Genomic science is increasingly central to the provision of health care. Producing and applying robust genomics knowledge is a complex endeavour in which no single individual, profession, discipline or community holds all the answers.  Engagement and involvement of diverse stakeholders can support alignment of societal and scientific interests, understandings and perspectives and promises better science and fairer outcomes. In this context we argue for F.A.I.R.E.R. data and data use that is Findable, Accessible, Interoperable, Reproducible, Equitable and Responsible. Yet there is a paucity of international guidance on how to engage publics, patients and participants in genomics. To support meaningful and effective engagement and involvement we developed an Engagement Framework for involving and engaging participants, patients and publics in genomics research and health implementation . The Engagement Framework is intended to support all those working in genomics research, medicine, and healthcare to deliberatively consider approaches to participant, patient and public engagement and involvement in their work. Through a series of questions, the Engagement Framework prompts new ways of thinking about the aims and purposes of engagement, and support reflection on the strengths, limitations, likely outcomes and impacts of choosing different approaches to engagement. To guide genomics activities, we describe four themes and associated questions for deliberative reflection: (i) fairness; (ii) context; (iii) heterogeneity, and (iv) recognising tensions and conflict. The four key components in the Engagement provide a framework to assist those involved in genomics to reflect on decisions they make for their initiatives, including the strategies selected, the participant, patient and public stakeholders engaged, and the anticipated goals. The Engagement Framework is one step in an actively evolving process of building genomics research and implementation cultures which foster responsible leadership and are attentive to objectives which increase equality, diversity and inclusion in participation and outcomes.

Background: This study aims to identify a novel potential use for web portals in health care and health research: their adoption for the purposes of rapidly sharing health research findings with clinicians, scientists, and patients. In the era of precision medicine and learning health systems, the translation of research findings into targeted therapies depends on the availability of big data and emerging research results. Web portals may work to promote the availability of novel research, working in tandem with traditional scientific publications and conference proceedings. Objective: This study aims to assess the potential use of web portals, which facilitate the sharing of health research findings among researchers, clinicians, patients, and the public. It also summarizes the potential legal, ethical, and policy implications associated with such tools for public use and in the management of patient care for complex diseases. Methods: This study broadly adopts the methods for scoping literature reviews outlined by Arskey and O’Malley in 2005. Raised by the integration of web portals into patient care for complex diseases, we systematically searched 3 databases, PubMed, Scopus, and WestLaw Next, for sources describing web portals for sharing health research findings among clinicians, researchers, and patients and their associated legal, ethical, and policy challenges. Of the 719 candidate source citations, 22 were retained for the review. Results: We found varied and inconsistent treatment of web portals for sharing health research findings among clinicians, researchers, and patients. Although the literature supports the view that portals of this kind are potentially highly promising, they remain novel and are not yet widely adopted. We also found a wide range of discussions on the legal, ethical, and policy issues related to the use of web portals to share research data. Conclusions: We identified 5 important legal and ethical challenges: privacy and confidentiality, patient health literacy, equity, training, and decision-making. We contend that each of these has meaningful implications for the increased integration of web portals into clinical care.

The Global Alliance for Genomics and Health (GA4GH) aims to accelerate biomedical advances by enabling the responsible sharing of clinical and genomic data through both harmonized data aggregation and federated approaches. The decreasing cost of genomic sequencing (along with other genome-wide molecular assays) and increasing evidence of its clinical utility will soon drive the generation of sequence data from tens of millions of humans, with increasing levels of diversity. In this perspective, we present the GA4GH strategies for addressing the major challenges of this data revolution. We describe the GA4GH organization, which is fueled by the development efforts of eight Work Streams and informed by the needs of 24 Driver Projects and other key stakeholders. We present the GA4GH suite of secure, interoperable technical standards and policy frameworks and review the current status of standards, their relevance to key domains of research and clinical care, and future plans of GA4GH. Broad international participation in building, adopting, and deploying GA4GH standards and frameworks will catalyze an unprecedented effort in data sharing that will be critical to advancing genomic medicine and ensuring that all populations can access its benefits.

Despite the plethora of empirical studies conducted to date, debate continues about whether and to what extent results should be returned to participants of genomic research. We aimed to systematically review the empirical literature exploring stakeholders’ perspectives on return of individual research results (IRR) from genomic research. We examined preferences for receiving or willingness to return IRR, and experiences with either receiving or returning them. The systematic searches were conducted across five major databases in August 2018 and repeated in April 2020, and included studies reporting findings from primary research regardless of method (quantitative, qualitative, mixed). Articles that related to the clinical setting were excluded. Our search identified 221 articles that met our search criteria. This included 118 quantitative, 69 qualitative and 34 mixed methods studies. These articles included a total number of 118,874 stakeholders with research participants (85,270/72%) and members of the general public (40,967/35%) being the largest groups represented. The articles spanned at least 22 different countries with most (144/65%) being from the USA. Most (76%) discussed clinical research projects, rather than biobanks. More than half (58%) gauged views that were hypothetical. We found overwhelming evidence of high interest in return of IRR from potential and actual genomic research participants. There is also a general willingness to provide such results by researchers and health professionals, although they tend to adopt a more cautious stance. While all results are desired to some degree, those that have the potential to change clinical management are generally prioritized by all stakeholders. Professional stakeholders appear more willing to return results that are reliable and clinically relevant than those that are less reliable and lack clinical relevance. The lack of evidence for significant enduring psychological harm and the clear benefits to some research participants suggest that researchers should be returning actionable IRRs to participants.

Polygenic risk scores (PRSs) aggregate the many small effects of alleles across the human genome to estimate the risk of a disease or disease-related trait for an individual. The potential benefits of PRSs include cost-effective enhancement of primary disease prevention, more refined diagnoses and improved precision when prescribing medicines. However, these must be weighed against the potential risks, such as uncertainties and biases in PRS performance, as well as potential misunderstanding and misuse of these within medical practice and in wider society. By addressing key issues including gaps in best practices, risk communication and regulatory frameworks, PRSs can be used responsibly to improve human health. Here, the International Common Disease Alliance’s PRS Task Force, a multidisciplinary group comprising expertise in genetics, law, ethics, behavioral science and more, highlights recent research to provide a comprehensive summary of the state of polygenic score research, as well as the needs and challenges as PRSs move closer to widespread use in the clinic.

The implementation of precision medicine and next-generation sequencing technologies in the field of oncology is a novel approach being more widely studied and used in cases of high-risk primary and recurrent malignancies. Leukemias are the second most common cause of cancer-related mortality in children and the sixth most in adults. Relapsed leukemia represents a major component of the population that may benefit from genomic sequencing. However, ethical and analytic challenges arise when considering sequencing of biologic samples obtained from patients with relapsed leukemia following allogeneic hematopoietic stem-cell transplantation. Blood from the recipient after transplantation would include donor-derived cells and thus, genomic sequencing of recipient blood will interrogate the donor germline in addition to the somatic genetic profile of the leukemia cells and the recipient germline. This is a situation for which the donor will not have typically provided consent and may be particularly problematic if actionable secondary or incidental findings related to the donor are uncovered. We present the challenges raised in this scenario and provide strategies to mitigate this risk.

In the face of the COVID-19 pandemic, Canadian researchers and public health agencies have struggled to assemble and disseminate the large quantities of information required to perform research that would promote evidence-based public health interventions. Barriers to information exchange include the decentralized information collection efforts of public health laboratories, researchers, and healthcare institutions, and a lack of incentives for such institutions to invest in the harmonization and centralization of information. Further, Canadian data protection legislation, public health law, and the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (TCPS-2) all create a complex landscape of rules applicable to such information exchanges. Our legal analysis indicates that numerous lawful paths to the pan-Canadian dissemination of information exist. One approach is to anonymize information in reliance on a combination of de- identification methods and organizational controls. Invoking the broad information collection powers of governments and government agencies to obtain and transmit the necessary information is another potential approach. The statutory powers of public health agencies can also be relied on to mobilize information for reasons of public health surveillance or public health intervention. Last, access can be requested to the data of health information custodians, such as hospitals, for research purposes. To promote the implementation of a harmonized approach to health information exchange in Canada, the adoption of new laws or of regulations to existing laws is required. The applicable laws are unharmonized, inconsistent, and sometimes ambiguous. Moreover, these laws can impose undue restrictions or a significant administrative burden on the use of information. To ensure that Canada’s provincial and federal public health agencies are capable of responding to emergent public health crises in a coordinated manner, laws or regulations should be implemented to establish that data sharing is permitted for public health purposes, including research, all throughout Canada according to simple and uniform preconditions. If these changes are not implemented, Canada will struggle to match the efforts made by other members of the G20 to protect the health of its citizens and to address future epidemic and pandemic threats.

In the Canadian Alliance for Healthy Hearts and Minds (CAHHM) cohort, participants underwent magnetic resonance imaging (MRI) of the brain, heart, and abdomen, that generated incidental findings (IFs). The approach to managing these unexpected results remain a complex issue. Our objectives were to describe the CAHHM policy for the management of IFs, to understand the impact of disclosing IFs to healthy research participants, and to reflect on the ethical obligations of researchers in future MRI studies.

Anticipatory policy for gene editing requires assessing public opinion about this new technology. Although previous surveys have examined respondents’ views on the moral acceptability of various hypothetical uses of CRISPR, they have not considered whether these scenarios are perceived as plausible. Research in construal level theory indicates that participants make different moral judgments about scenarios seen as likely or near and those seen as unlikely or distant. Therefore, we surveyed a representative sample of 400 Americans and Canadians about both the likelihood and the permissibility of 23 commonly discussed uses of gene editing. Respondents with more knowledge of gene editing generally thought these applications would be more likely within the next 20 years. There was a strong positive relationship between the perceived likelihood and permissibility of most CRISPR applications. Our results suggest that ongoing public engagement efforts for gene editing could be improved by taking its perceived time-frames into account.

Abstract Debates surrounding genetic privacy have taken on different forms over the past 30 years. Taking genetic privacy to mean an interest that individuals, families, or even communities have with respect to genetic information, we examine the metaphors used in these debates to chronicle the development of genetic privacy. In 1990–2000, we examine claims for ownership and of ‘humanity’ spurred by the launch of the Human Genome Project and related endeavors. In 2000–2010, we analyze the interface of law and ethics with research infrastructures such as biobanks, for which notions of citizenship and ‘public goods’ were central. In 2010–2020, we detail the relational turn of genetic privacy in response of large international research consortia and big data. Although each decade had its leading conceptions of genetic privacy, the subject is neither strictly chronological nor static. We conclude with reflections on the nature of genetic privacy and the necessity to bring together the unique and private genetic self with the human other.

On 16 July 2020, the Court of Justice of the European Union issued their decision in the Schrems II case concerning Facebook’s transfers of personal data from the EU to the US. The decision may have significant effects on the legitimate transfer of personal data for health research purposes from the EU. This article aims: (i) to outline the consequences of the Schrems II decision for the sharing of personal data for health research between the EU and third countries, particularly in the context of the COVID-19 pandemic; and, (ii) to consider certain options available to address the consequences of the decision and to facilitate international data exchange for health research moving forward.

Our research compares the ethical and institutional conditions that govern the sharing and secondary use of longitudinal population health data from multiple cohorts. The data use and data sharing conditions applicable to 27 population health cohorts were assessed. This assessment was performed in consulting the informed consent materials and institutional policies applicable to the use of data. Descriptions drawn from the research ethics consent materials were refined through dialog with the institutional staff responsible for overseeing access to data, where possible. Our results demonstrate that data of longitudinal population health cohorts assessed can generally be shared and used for secondary purposes. However, the purposes of secondary use and the preconditions applicable thereto are highly variable. Heterogeneous use conditions can also impede the storage of legacy research data and the pooling thereof for the purpose of common reuse.

Biomedical research based on the sharing and use of ever larger volumes of samples and data is increasingly becoming an essential component of scientific discovery. The success of biobanking and genomic research is dependent on the broad sharing of resources for use by investigators. However, important ethical challenges need to be addressed for the sample and data sharing to be successful. Despite low- and middle-income countries (LMICs) carrying a higher burden of disease, biomedical research conducted to date has mainly focused on high-income countries. In order for LMICs to benefit from the advances in such research, normative documents (such as laws and guidelines) play a significant role in allowing LMIC projects to partake and be represented in global biomedical research. The administration and management of the ethical aspects of biobanking, including informed consent, are key components in ensuring that samples and data can legally and ethically be used and shared. As part of its support to the LMIC biobanks, the International Agency for Research on Cancer (IARC) established a biobank and population cohort building network (BCNet) in 2013 with the aims of providing support (including education and training) and facilitating the development and improvement of biobanking infrastructure in LMICs. A comparative analysis of the laws and guidelines in BCNet countries was completed to highlight some of the ethical and legal issues related to biobanking in LMICs and to identify examples of effective systems of governance already in operation.

Le problème de la discrimination génétique est associé aux tests génétiques depuis des décennies, bien qu'étayé par une quantité limitée de preuves dans des contextes spécifiques. Au Canada, l'adoption de la Loi sur la non-discrimination génétique (LNDG) en 2017 a donné lieu à une bataille judiciaire de trois ans, relative à la constitutionnalité de certaines dispositions de la loi, initiée par le gouvernement du Québec. La Cour d’appel du Québec a formulé une opinion le 21 décembre 2018 selon laquelle les articles 1 à 7 de la LNDG, faute d’objet de droit criminel, étaient ultra vires de la compétence criminelle du Parlement fédéral. Dans le Renvoi relatif à la Loi sur la non-discrimination génétique, la Cour suprême du Canada a confirmé la validité constitutionnelle de la LNDG, une majorité de cinq juges déclarant que l'objectif des articles contestés constituait un exercice valide du pouvoir du Parlement fédéral de légiférer en matière de droit criminel. Dans un examen critique de cette décision, nous soutenons que le raisonnement des juges majoritaires contient de graves erreurs de droit et de fait qui soulèvent des préoccupations tant du point de vue du droit constitutionnel que du point de vue scientifique. En accord avec la minorité, nous concluons que la majorité des juges n'ont pas correctement défini le caractère véritable des dispositions contestées, ni appliqué la norme de l’appréhension raisonnée de préjudice. Nous pensons en outre que la majorité a réservé un traitement cursif des faits, montrant un intérêt étonnamment limité pour la promotion de l'élaboration de politiques fondées sur des preuves scientifiques, à une époque où la science est omniprésente dans toutes les sphères des activités humaines.

Background In 2019, the Australian life insurance industry introduced a partial moratorium (ban) limiting the use of genetic test results in life insurance underwriting. The moratorium is industry self-regulated and applies only to policies below certain financial limits (eg, $500 000 of death cover). Methods We surveyed Australian health professionals (HPs) who discuss genetic testing with patients, to assess knowledge of the moratorium; reported patient experiences since its commencement; and HP views regarding regulation of genetic discrimination (GD) in Australia. Results Between April and June 2020, 166 eligible HPs responded to the online survey. Of these, 86% were aware of the moratorium, but <50% had attended related training/information sessions. Only 16% answered all knowledge questions correctly, yet 69% believed they had sufficient knowledge to advise patients. Genetics HPs’ awareness and knowledge were better than non-genetics HPs’ (p<0.05). There was some reported decrease in patients delaying/declining testing after the moratorium’s introduction, however, 42% of HPs disagreed that patients were more willing to have testing post-moratorium. Although many (76%) felt the moratorium resolved some GD concerns, most (88%) still have concerns, primarily around self-regulation, financial limits and the moratorium’s temporary nature. Almost half (49%) of HPs reported being dissatisfied with the moratorium as a solution to GD. The majority (95%) felt government oversight is required, and 93% felt specific Australian legislation regarding GD is required. Conclusion While the current Australian moratorium is considered a step forward, most HPs believe it falls short of an adequate long-term regulatory solution to GD in life insurance.

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.

The success of risk-stratified approaches in improving population-based breast cancer screening programs depends in no small part on women’s buy-in. Fear of genetic discrimination (GD) could be a potential barrier to genetic testing uptake as part of risk assessment. Thus, the objective of this study was twofold. First, to evaluate Canadian women’s knowledge of the legislative context governing GD. Second, to assess their concerns about the possible use of breast cancer risk levels by insurance companies or employers. We use a cross-sectional survey of 4293 (age: 30–69) women, conducted in four Canadian provinces (Alberta, British Colombia, Ontario and Québec). Canadian women’s knowledge of the regulatory framework for GD is relatively limited, with some gaps and misconceptions noted. About a third (34.7%) of the participants had a lot of concerns about the use of their health information by employers or insurers; another third had some concerns (31.9%), while 20% had no concerns. There is a need to further educate and inform the Canadian public about GD and the legal protections that exist to prevent it. Enhanced knowledge could facilitate the implementation and uptake of risk prediction informed by genetic factors, such as the risk-stratified approach to breast cancer screening that includes risk levels.

Newer data platforms offer increased opportunity to share multidimensional health data with research participants, but the preferences of participants for which data to receive and how is evolving. Our objective is to describe the preferences and expectations of participants for the return of individual research results within Project Baseline Health Study (PBHS). The PBHS is an ongoing, multicenter, longitudinal cohort study with data from four initial enrollment sites. PBHS participants are recruited from the general population along with groups enriched for heart disease and cancer disease risk. Cross-sectional data on return of results were collected in 2017–2018 from an (1) in-person enrollment survey (n = 1,890), (2) benchmark online survey (n = 1,059), and (3) participant interviews (n = 21). The main outcomes included (1) preferences for type of information to be added next to returned results, (2) participant plans for sharing returned results with a non-study clinician, and (3) choice to opt-out of receiving genetic results. Results were compared by sociodemographic characteristics. Enrollment and benchmark survey respondents were 57.1% and 53.5% female, and 60.0% and 66.2% white, respectively. Participants preferred the following data types be added to returned results in the future: genetics (29.9%), heart imaging, (16.4%), study watch (15.8%), and microbiome (13.3%). Older adults (OR 0.60, 95% CI: 0.41–0.87) were less likely to want their genetic results returned next. Forty percent of participants reported that they would not share all returned results with their non–study clinicians. Black (OR 0.64, 95% CI 0.43–0.95) and Asian (OR 0.47, 95% CI 0.30–0.73) participants were less likely, and older participants more likely (OR 1.45–1.61), to plan to share all results with their clinician than their counterparts. At enrollment, 5.8% of participants opted out of receiving their genetics results. The study showed that substantial heterogeneity existed in participant’s preferences and expectations for return of results, and variations were related to sociodemographic characteristics.

Technological innovations including risk-stratification algorithms and large databases of longitudinal population health data and genetic data are allowing us to develop a deeper understanding how individual behaviors, characteristics, and genetics are related to health risk. The clinical implementation of risk-stratified screening programmes that utilise risk scores to allocate patients into tiers of health risk is foreseeable in the future. Legal and ethical challenges associated with risk-stratified cancer care must, however, be addressed. Obtaining access to the rich health data that are required to perform risk-stratification, ensuring equitable access to risk-stratified care, ensuring that algorithms that perform risk-scoring are representative of human genetic diversity, and determining the appropriate follow-up to be provided to stratification participants to alert them to changes in their risk score are among the principal ethical and legal challenges. Accounting for the great burden that regulatory requirements could impose on access to risk-scoring technologies is another critical consideration.

Letter to the Editor

The Global Alliance for Genomics and Health has approved a policy for the return of clinically actionable genomic research results, the first such policy approved by an international body. The policy acknowledges the potential medical benefits to millions of individuals who are participating in genomics research. It ties the pace of implementation to each country’s clinical standards, including for the return of secondary findings, and urges funders to set aside resources to support responsible return.

Our article aims to provide a comprehensive portrayal of how seven Asian jurisdictions have sought to address the challenge of genetic discrimination (GD) by presenting an analysis of the relevant legislation, policies, and practices. Based on our findings, policy discussion and action on preventing or mitigating GD have been narrowly framed in terms of employment, insurance, disability, marriage, and family planning. Except for South Korea, none of the jurisdictions we examined has adopted specific legislation to prevent GD. However, for Asia to truly benefit from its recent scientific and technological progress in genomics, we highlight the need for these jurisdictions to engage more proactively with the challenges of GD through a coordinated regulatory and governance mechanism.

Data on the modalities of disclosing genomic secondary findings (SFs) remain scarce. We explore cancer patients’ and the general public’s perspectives about disclosing genomic SFs and the modalities of such disclosure.

The highly sensitive nature of genomic and associated clinical data, coupled with the consent-related vulnerabilities of children together accentuate ethical, legal and social issues (ELSI) concerning data sharing. The Key Implications of Data Sharing (KIDS) framework was therefore developed to address a need for institutional guidance on genomic data governance but has yet to be validated among data sharing practitioners in practice settings. This study qualitatively explored areas of consensus and dissensus of the KIDS Framework from the perspectives of Canadian clinician-scientists, genomic researchers, IRB members, and pediatric ethicists.

Early detection of breast cancer through screening reduces breast cancer mortality. The benefits of screening must also be considered within the context of potential harms (e.g., false positives, overdiagnosis). Furthermore, while breast cancer risk is highly variable within the population, most screening programs use age to determine eligibility. A risk-based approach is expected to improve the benefit-harm ratio of breast cancer screening programs. The PERSPECTIVE I&I (Personalized Risk Assessment for Prevention and Early Detection of Breast Cancer: Integration and Implementation) project seeks to improve personalized risk assessment to allow for a cost-effective, population-based approach to risk-based screening and determine best practices for implementation in Canada. This commentary describes the four inter-related activities that comprise the PERSPECTIVE I&I project. 1: Identification and validation of novel moderate to high-risk susceptibility genes. 2: Improvement, validation, and adaptation of a risk prediction web-tool for the Canadian context. 3: Development and piloting of a socio-ethical framework to support implementation of risk-based breast cancer screening. 4: Economic analysis to optimize the implementation of risk-based screening. Risk-based screening and prevention is expected to benefit all women, empowering them to work with their healthcare provider to make informed decisions about screening and prevention.

Medical genetic services are facing an unprecedented demand for counseling and testing for hereditary breast and ovarian cancer (HBOC) in a context of limited resources. To help resolve this issue, a collaborative oncogenetic model was recently developed and implemented at the CHU de Québec-Université Laval; Quebec; Canada. Here, we present the protocol of the C-MOnGene (Collaborative Model in OncoGenetics) study, funded to examine the context in which the model was implemented and document the lessons that can be learned to optimize the delivery of oncogenetic services. Within three years of implementation, the model allowed researchers to double the annual number of patients seen in genetic counseling. The average number of days between genetic counseling and disclosure of test results significantly decreased. Group counseling sessions improved participants’ understanding of breast cancer risk and increased knowledge of breast cancer and genetics and a large majority of them reported to be overwhelmingly satisfied with the process. These quality and performance indicators suggest this oncogenetic model offers a flexible, patient-centered and efficient genetic counseling and testing for HBOC. By identifying the critical facilitating factors and barriers, our study will provide an evidence base for organizations interested in transitioning to an oncogenetic model integrated into oncology care; including teams that are not specialized but are trained in genetics.

La recherche empirique sur la problématique de la discrimination génétique (DG) au Québec est généralement limitée. À ce titre, cette étude vise, au moyen d’une méthodologie qualitative, à explorer et à recueillir les opinions, les expériences et les connaissances des Québécois à l’égard de la DG. En concordance avec les objectifs exploratoires de cette étude, nous avons choisi l’approche du forum en ligne afin de pouvoir extraire des données qualitatives représentant le plus fidèlement possible les perspectives du public québécois sur différents thèmes touchant la DG. L’expérience du forum indique que des craintes tangibles existent par rapport à la DG au Québec, et que s’exprime le besoin d’un débat de société sur cet important enjeu faisant partie intégrante de la révolution génétique et des soins de santé personnalisés. , Empirical research regarding genetic discrimination (GD) in the province of Quebec is largely limited. As such, this study aims, through a qualitative methodology, to explore and collect the opinions, experiences and knowledge of Quebecers regarding GD. In accordance with the exploratory objectives of this study, we chose the online forum approach as a means to extract qualitative data that would most accurately represent the perspectives of the Quebec public on various themes relating to GD. Participants’ comments on the forum indicate that there are tangible fears concerning DG in Quebec as well as a need for social debate on this important issue, as an integral part of the genetic revolution and personalized healthcare.

The systemic challenges of the COVID-19 pandemic require cross-disciplinary collaboration in a global and timely fashion. Such collaboration needs open research practices and the sharing of research outputs, such as data and code, thereby facilitating research and research reproducibility and timely collaboration beyond borders. The Research Data Alliance COVID-19 Working Group recently published a set of recommendations and guidelines on data sharing and related best practices for COVID-19 research. These guidelines include recommendations for clinicians, researchers, policy- and decision-makers, funders, publishers, public health experts, disaster preparedness and response experts, infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations), and other potential users. These guidelines include recommendations for researchers, policymakers, funders, publishers and infrastructure providers from the perspective of different domains (Clinical Medicine, Omics, Epidemiology, Social Sciences, Community Participation, Indigenous Peoples, Research Software, Legal and Ethical Considerations). Several overarching themes have emerged from this document such as the need to balance the creation of data adherent to FAIR principles (findable, accessible, interoperable and reusable), with the need for quick data release; the use of trustworthy research data repositories; the use of well-annotated data with meaningful metadata; and practices of documenting methods and software. The resulting document marks an unprecedented cross-disciplinary, cross-sectoral, and cross-jurisdictional effort authored by over 160 experts from around the globe. This letter summarises key points of the Recommendations and Guidelines, highlights the relevant findings, shines a spotlight on the process, and suggests how these developments can be leveraged by the wider scientific community.

SARS-CoV-2 infection causing the novel coronavirus disease 2019 (COVID–19) has been responsible for more than 2.8 million deaths and nearly 125 million infections worldwide as of March 2021. In March 2020, the World Health Organization determined that the COVID–19 outbreak is a global pandemic. The urgency and magnitude of this pandemic demanded immediate action and coordination between local, regional, national, and international actors. In that mission, researchers require access to high-quality biological materials and data from SARS-CoV-2 infected and uninfected patients, covering the spectrum of disease manifestations. The “Biobanque québécoise de la COVID-19” (BQC19) is a pan–provincial initiative undertaken in Québec, Canada to enable the collection, storage and sharing of samples and data related to the COVID-19 crisis. As a disease-oriented biobank based on high-quality biosamples and clinical data of hospitalized and non-hospitalized SARS-CoV-2 PCR positive and negative individuals. The BQC19 follows a legal and ethical management framework approved by local health authorities. The biosamples include plasma, serum, peripheral blood mononuclear cells and DNA and RNA isolated from whole blood. In addition to the clinical variables, BQC19 will provide in-depth analytical data derived from the biosamples including whole genome and transcriptome sequencing, proteome and metabolome analyses, multiplex measurements of key circulating markers as well as anti-SARS-CoV-2 antibody responses. BQC19 will provide the scientific and medical communities access to data and samples to better understand, manage and ultimately limit, the impact of COVID-19. In this paper we present BQC19, describe the process according to which it is governed and organized, and address opportunities for future research collaborations. BQC19 aims to be a part of a global communal effort addressing the challenges of COVID–19.

This article identifies the potential sources of inequity in three stages of integrating cystic fibrosis personalized medicines into the Canadian healthcare system and proposes mitigating strategies: (1) clinical research and diagnostic testing; (2) regulatory oversight and market authorization; and (3) implementation into the healthcare system. There is concern that differential access will cast a dark shadow over personalized medicine by stratifying the care that groups of patients will receive—not only based on their genetic profiles, but also on the basis of their socioeconomic status. Furthermore, there is a need to re-evaluate regulatory and market approval mechanisms to accommodate the unique nature of personalized medicines. Physical and financial accessibility ought to be remedied before personalized medicines can be equitably delivered to patients. This article identifies the socio–ethical and legal challenges at each stage and recommends mitigating policy solutions.

Genetic discrimination has been a public concern for decades but supported by limited evidence. Following a reference from the Quebec government, the Court of Appeal of Quebec considered sections 1 to 7 of the Genetic Non-Discrimination Act (GNDA) were ultra vires of Parliament’s criminal jurisdiction (2018). In a 5-4 decision, the Supreme Court of Canada upheld the validity of the GNDA (2020). We contend that the majority’s reasoning contains serious errors in law and fact, raising constitutional and scientific concerns. We believe the majority incorrectly determined both the pith and substance of the provisions and the reasoned apprehension of harm standard.

The COVID-19 pandemic has underscored the need for new ways of thinking about data protection. This is especially so in the case of health research with children. The responsible use of children’s data plays a key role in promoting children’s well-being and securing their right to health and to privacy. In this article, we contend that a contextual approach that appropriately balances children’s legal and moral rights and interests is needed when thinking about data protection issues with children. We examine three issues in health research through a child-focused lens: consent to data processing, data retention, and data protection impact assessments. We show that these issues present distinctive concerns for children and that the General Data Protection Regulation provides few bright-line rules. We contend that there is an opportunity for creative approaches to children’s data protection when child-specific principles, such as the best interests of the child and the child’s right to be heard, are put into dialogue with the structure and logic of data protection law.

INTRODUCTION: Childhood overweight and obesity (OWO) is a primary global health challenge. Childhood OWO prevention is now a public health priority in China. The Sino-Canadian Healthy Life Trajectories Initiative (SCHeLTI), one of four trials being undertaken by the international HeLTI consortium, aims to evaluate the effectiveness of a multifaceted, community-family-mother-child intervention on childhood OWO and non-communicable diseases risk. METHODS AND ANALYSIS: This is a multicentre, cluster-randomised, controlled trial conducted in Shanghai, China. The unit of randomisation is the service area of Maternal Child Health Units (N=36). We will recruit 4500 women/partners/families in maternity and district level hospitals. Participants in the intervention group will receive a multifaceted, integrated package of health promotion interventions beginning in preconception or in the first trimester of pregnancy, continuing into infancy and early childhood. The intervention, which is centred on a modified motivational interviewing approach, will target early-life maternal and child risk factors for adiposity. Through the development of a biological specimen bank, we will study potential mechanisms underlying the effects of the intervention. The primary outcome for the trial is childhood OWO (body mass index for age ≥85th percentile) at 5 years of age, based on WHO sex-specific standards. The study has a power of 0.8 (α=0.05) to detect a 30% risk reduction in the proportion of children with OWO at 5 years of age, from 24.4% in the control group to 17% in the intervention group. Recruitment was launched on 30 August 2018 for the pilot study and 10 January 2019 for the formal study. ETHICS AND DISSEMINATION: The study has been approved by the Medical Research Ethics Committee of the International Peace Maternity and Child Health Hospital in Shanghai, China, and the Research Ethics Board of the Centre Intégré Universitaire de Santé et Services Sociaux de l'Estrie-CHUS in Sherbrooke, Canada. Data sharing policies are consistent with the governance policy of the HeLTI consortium and government legislation. TRIAL REGISTRATION NUMBER: ChiCTR1800017773. PROTOCOL VERSION: November 11, 2020 (Version #5).

Children with rare and common diseases now undergo whole genome sequencing (WGS) in clinical and research contexts. Parents sometimes request access to their child's raw genomic data, to pursue their own analyses or for onward sharing with health professionals and researchers. These requests raise legal, ethical, and practical issues for professionals and parents alike. The advent of widespread WGS in pediatrics occurs in a context where privacy and data protection law remains focused on giving individuals control-oriented rights with respect to their personal information. Acting in their child's stead and in their best interests, parents are generally the ones who will be exercising these informational rights on behalf of the child. In this paper, we map the contours of parental authority to access their child's raw genomic data. We consider three use cases: hospital-based researchers, healthcare professionals acting in a clinical-diagnostic capacity, and “pure” academic researchers at a public institution. Our research seeks to answer two principal questions: Do parents have a right of access to their child's raw WGS data? If so, what are the limits of this right? Primarily focused on the laws of Ontario, Canada's most populous province, with a secondary focus on Canada's three other most populous provinces (Quebec, British Columbia, and Alberta) and the European Union, our principal findings include (1) parents have a general right of access to information about their children, but that the access right is more capacious in the clinical context than in the research context; (2) the right of access extends to personal data in raw form; (3) a consideration of the best interests of the child may materially limit the legal rights of parents to access data about their child; (4) the ability to exercise rights of access are transferred from parents to children when they gain decision-making capacity in both the clinical and research contexts, but with more nuance in the former. With these findings in mind, we argue that professional guidelines, which are concerned with obligations to interpret and return results, may assist in furthering a child's best interests in the context of legal access rights. We conclude by crafting recommendations for healthcare professionals in the clinical and research contexts when faced with a parental request for a child's raw genomic data.

Risk-stratified screening for breast cancer (BC) is increasingly considered as a promising approach. However, its implementation is challenging and needs to be acceptable to women. We examined Canadian women’s attitudes towards, comfort level about, and willingness to take part in BC risk-stratified screening. We conducted an online survey in women aged 30 to 69 years in four Canadian provinces. In total, 4293 women completed the questionnaire (response rate of 63%). The majority of women (63.5% to 72.8%) expressed favorable attitudes towards BC risk-stratified screening. Most women reported that they would be comfortable providing personal and genetic information for BC risk assessment (61.5% to 67.4%) and showed a willingness to have their BC risk assessed if offered (74.8%). Most women (85.9%) would also accept an increase in screening frequency if they were at higher risk, but fewer (49.3%) would accept a reduction in screening frequency if they were at lower risk. There were few differences by province; however, outcomes varied by age, education level, marital status, income, perceived risk, history of BC, prior mammography, and history of genetic test for BC (all p ≤ 0.01). Risk-based BC screening using multifactorial risk assessment appears to be acceptable to most women. This suggests that the implementation of this approach is likely to be well-supported by Canadian women.

To better understand the barriers and drivers to implementing a centralized rare disease database for the integration of rare disease research and clinical data across Canada by facilitating data sharing (Genome Canada 2018), we surveyed stakeholders from the Canadian rare disease research community using a two-round survey. Patient privacy and confidentiality, regulatory compliance, lack of funding, and IT infrastructure are relevant considerations in any data sharing context, especially when it involves sensitive genetic information as in the health sector.

Mitochondrial replacement therapy (MRT) in Canada is considered a criminal offense according to article 5(1)(f) of the Assisted Human Reproduction Act (AHRA) (2004). The Act prohibits any practice that modifies the genome of “a human being or in vitro embryo such that the alteration is capable of being transmitted to descendants.” We carried out 32 semi-structured interviews with clinicians, researchers, patient groups, egg donors, and members of the public to explore their attitudes toward the clinical implementation of MRT in Canada. Our interview guide was informed by the socioethical, legal, and scientific literature of MRT. We used a thematic analysis to identify and analyze emerging themes and sub-themes. Our findings were divided into five broad themes: (i) an outdated criminal ban, (ii) motives for using MRT, (iii) terminology, (iv) practical and theoretical risks and benefits, and (v) the feasibility of clinical translation in Canada. Although the public and stakeholders’ views on the feasibility of foreseeable translation of MRT in Canadian clinics varied, there was consensus on conducting an overdue review of the current AHRA ban on MRT.

Here, we argue that, in line with the dramatic increase in the collection, storage and curation of human genomic data for biomedical research, genomic data repositories and consortia have adopted governance frameworks to both enable wide access and protect against possible harms. However, the merits and limitations of different governance frameworks in achieving these twin aims are a matter of ongoing debate in the scientific community; indeed, best practices and points for consideration are notably absent in devising governance frameworks for genomic databases. According to our collective experience in devising and assessing governance frameworks, we identify five key functions of ‘good governance’ (or ‘better governance’) and three areas in which trade-offs should be considered when specifying policies within those functions. We apply these functions as a benchmark to describe, as an example, the governance frameworks of six large-scale international genomic projects.

Anti-selection occurs when information asymmetry exists between an insurer and an applicant. When an applicant knows that they are at high risk of loss, but the insurer does not, the applicant may try to exploit this knowledge differential to secure insurance at a lower premium that does not match risk. Predictive genetic testing could lead to anti-selection if individuals, but not insurers, learn of genetic risk. Yet, to address fear of discrimination, several countries have, or are considering, limitations on insurers’ use of predictive genetic test results. In this paper, we discuss anti-selection theory and modeling and illustrate how regulation regarding insurer use of predictive genetic test results could impact anti-selection in insurance markets. The extent of this impact turns on how much individuals alter their insurance purchasing behavior following predictive genetic testing. At first blush it may seem likely that those who learn that they are at high-risk of a genetic condition would attempt to gain greater coverage. However, we highlight several domains of on-the-ground realities that challenge this baseline assumption. These real-world considerations should be incorporated into modeling of anti-selection to truly assess the potential impacts of regulation limiting insurer use of predictive genetic testing.

An innovative approach to adapt breast cancer screening to the individual risk level of each woman may soon be implemented in the Québec clinical context. Requiring both a genetic analysis as well as an estimation using a calculation algorithm, this approach may well reveal a lack of specialized health professionals to implement such changes. To address this issue, stakeholders suggested increasing the involvement of nurses by allowing them to initiate genetic testing, advise on follow-up options and order imaging exams. Can this increased involvement of nurses –at the frontier of the practice of medicine– could be embodied in the current legal framework? We identified four legal options that would allow increasing the involvement of nurses: A) the National Public Health Program, B) the sharing of functions reserved to doctors, C) the use of collective prescription, and D) delegation to specialized nurse practitioners. After examining each of these options with regards to their legality under the current legal framework regulating the practice of nursing, we concluded that each option could be pursued individually or together with one or more of the other proposed options to achieve an increased involvement of nurses.

To mark the beginning of National Minority Health Month, The American Journal of Managed Care® (AJMC®) takes a look at racial inequities in the COVID-19 vaccine rollout and speaks with one expert who fears reality is worse than data indicate.

Genetics and genomics are playing increasingly important roles in the Canadian health car…

The last fifteen years have seen the emergence of Public Health Genomics (PHG), a multidisciplinary field related to the effective and responsible translation of genome-based knowledge and technologies to improve population health. While at the beginning the main concern of PHG was that genetic/genomic applications should be evaluated rigorously before entering into clinical and public health (PH) practice, now the main matter is around the fact that there are some genetic/genomic applications with proved efficacy and cost-effectiveness that should be implemented and become citizens’ rights. In any case, there is a critical need for a robust evaluation process, that takes into account also context-related dimensions (delivery models, economic evaluation and organizational aspects) to facilitate the implementation of these technologies. Systematic reviews of full economic evaluations of genetic/genomic applications are of paramount importance to identify all feasible health programs involving a defined use of a particular genetic/genomic application and to recognize which health programs can maximize the value of that genetic/genomic application. Cost-effectiveness analyses may be useful also in the early stages of the evaluation process to assess which characteristics of a genetic/genomic application need to be improved. Finally, the implementation of genetic/genomics applications requires specific training efforts for public health professional to increase their current level of competence. All these issues are addressed in this chapter, using the population health perspective and the point of view of PH.

Every month, a member of the MRM Network is writing about stem cells and regenerative medicine from a different perspective.

The right to benefit from science and its applications is one of the least studied, discussed and applied human rights. In the current time of globalization, characterized by the rapid advancement of science and its technological applications, as well as by increased flows of scientific data, there is a growing need to fully awaken the right of everyone to enjoy the benefits of science. This would enable science to serve better the humanitarian purposes of the law, as well as foster scientific and technological development through data sharing. This paper contributes to the awakening of the right by exploring it doctrinally with the aim of ascertaining its normative content by reference to the preparatory works of Article 15 ICESCR and especially the subsequent state practice in its application. Based on the evidence, it will be argued that today, the right to benefit from science has two aspects – first, the right to access scientific knowledge and information and second, the right to benefit from scientific applications. It will be shown that the first aspect of the right is increasingly reflected in the practice of states and international organizations and has important implications for the regulation and sharing of big genomic data.

Background : Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belongs to a subgroup of coronaviruses rampant in bats for centuries. It caused the coronavirus disease 2019 (COVID-19) pandemic. Most patients recover, but a minority of severe cases experience acute respiratory distress or an inflammatory storm devastating many organs that can lead to patient death. The spread of SARS-CoV-2 was facilitated by the increasing intensity of air travel, urban congestion and human contact during the past decades. Until therapies and vaccines are available, tests for virus exposure, confinement and distancing measures have helped curb the pandemic. Vision : The COVID-19 pandemic calls for safeguards and remediation measures through a systemic response. Self-organizing initiatives by scientists and citizens are developing an advanced collective intelligence response to the coronavirus crisis. Their integration forms Olympiads of Solidarity and Health. Their ability to optimize our response to COVID-19 could serve as a model to trigger a global metamorphosis of our societies with far-reaching consequences for attacking fundamental challenges facing humanity in the 21 st century. Mission : For COVID-19 and these other challenges, there is no alternative but action. Meeting in Paris in 2003, we set out to "rethink research to understand life and improve health." We have formed an international coalition of academia and industry ecosystems taking a systems medicine approach to understanding COVID-19 by thoroughly characterizing viruses, patients and populations during the pandemic, using openly shared tools. All results will be publicly available with no initial claims for intellectual property rights. This World Alliance for Health and Wellbeing will catalyze the creation of medical and health products such as diagnostic tests, drugs and vaccines that become common goods accessible to all, while seeking further alliances with civil society to bridge with socio-ecological and technological approaches that characterise urban systems, for a collective response to future health emergencies.

Researchers must collaborate globally to rapidly respond to the COVID-19 pandemic. In Europe, the General Data Protection Regulation (GDPR) regulates the processing of personal data, including health data of value to researchers. Even during a pandemic, research still requires a legal basis for the processing of sensitive data, additional justification for its processing, and a basis for any transfer of data outside Europe. The GDPR does provide legal grounds and derogations that can support research addressing a pandemic, if the data processing activities are proportionate to the aim pursued and accompanied by suitable safeguards. During a pandemic, a public interest basis may be more promising for research than a consent basis, given the high standards set out in the GDPR. However, the GDPR leaves many aspects of the public interest basis to be determined by individual Member States, which have not fully or uniformly made use of all options. The consequence is an inconsistent legal patchwork that displays insufficient clarity and impedes joint approaches. The COVID-19 experience provides lessons for national legislatures. Responsiveness to pandemics requires clear and harmonized laws that consider the related practical challenges and support collaborative global research in the public interest.

Effective responses to the COVID-19 pandemic require novel solutions for research and responsible data sharing. Biobanking presents itself as a key priority in furthering our understanding of COVID-19. In this article, we propose a tripartite approach to consent to create resources for research relating to COVID-19. The approach aims to link three levels of participation: COVID-19 patients, respiratory/infectious disease patients, and longitudinal study participants. We explore the potential approaches that can be taken to consent processes with these three participant groups. We furthermore describe an access model for both single-site and multi-site data and sample storage. Through dealing with these topics at a high level, the model may be adapted to local legal and ethical requirements while still pursuing its ultimate goal: the creation of a research infrastructure that supports transparent, strong, and open science.

Sharing data expediently for pandemic response purposes exposes healthcare providers in Canada to significant regulatory uncertainty. Duplicative and contradictory ethical and legal duties flowing from overlapping sources can stifle flows of medical data among clinicians, researchers, and institutions. Authorities should support caregivers and accelerate research by providing clear guidance to the health sector. Institutions should foster robust data stewardship and standardize their practices to those recognized among the international health informatics community. Reform is critical to ensuring Canadian healthcare providers can deliver efficient health responses that are integrated with dispersed and disparate national and international approaches.

Introduction: Biospecimens and associated data are invaluable tools in Genomics and Personalized Health (GAPH) research and can aid in the discovery of disease etiology and the development of therapeutics. Objective: To examine the experiences of patients invited to a particular GAPH study, Spectrometry in TIA Rapid Assessment (SpecTRA), and to explore broader biospecimen and data sharing preferences among a larger group of patients who had opted into a Permission to Contact for research program. Methods: An electronic survey was e-mailed to 515 participants. The survey was completed by 38% of participants, an unspecified number of whom were also SpecTRA participants. Results: Of those respondents who recalled participating in SpecTRA, 96% strongly agreed, agreed, or were neutral when asked if they received enough information to make an informed decision. Seventy-two percent agreed and 20% were neutral when asked if their study questions were addressed. Ninety-six percent of all respondents felt that SpecTRA's aim to develop a proteomic test for stroke was a worthwhile investment for health care, 98% said they were willing to provide a sample and/or information to facilitate the project's goals, and 96% to health research in general. Fifty-three percent of all participants suggested they would be comfortable sharing health information collected during SpecTRA with for-profit organizations, 87% with nonprofit organizations, and 38% said it matters to them where in the world their sample/information would be sent. Conclusions: Our results suggest that while there is room for improvement in providing adequate information to enable participants' understanding of the purpose of GAPH studies such as SpecTRA, patients are supportive of GAPH in general. Results also suggest that willingness to participate would likely be impacted by factors such as the study's commercial and national affiliations. This study indicates that further work is required to guide improvements on how the GAPH research community describes studies to potential participants, and to enable participation options that incorporate variable participant preferences.

Private companies have recently started to sell epigenetic tests to the public online, most of them without supervision by a physician. While the ethical and legal implications of direct-to-consumer genetic testing have received considerable attention over the past decades, other direct-to-consumer ‘omic’ tests have largely escaped scrutiny.

Genetic discrimination is one of the most pervasive challenges resulting from research and development in human genetics. To collaboratively study and prevent this ethical issue, we established an international Genetic Discrimination Observatory comprising a network of researchers and stakeholders from more than 19 jurisdictions.

Public health emergencies create a new context in which societies must balance competing priorities. Indeed, as a liberal society with individual rights at heart, we are confronting questions regarding how to further our collective, shared interests in fighting the global pandemic. Public health emergencies give the State distinct powers foreseen in laws adopted long ago

Canadian medical law orbits in a constellation of diverse legal influences spanning the course of the country’s legislative historical development. The provision of healthcare in Canada is characteristically decentralized, with 13 individual models of provincial and territorial healthcare policies that share overarching standards defined by federal statute. This chapter examines the laws of consent to medical treatment in Canada as well as related physician obligations, such as duties of disclosure and associated exceptions, medical liability and emerging challenges to informed consent. In this chapter, we present a comparative overview of the dominant legal scheme in both the common and civil law in Canada, approaching such review through the lens of developments in informatics as well as medical research and clinical practice. Our objective is to underscore how the laws of informed consent are shaped by the dynamic and ever-expanding medical field, and how this requires constant scrutiny guided by legal deference to scientific, medical, ethical, and administrative experts on technical matters.

In this paper, we outline the policy implications of mobile health research conducted at the international level. We describe the manner in which such research may have an international dimension and argue that it is not likely to be excluded from conventionally applicable international regulatory tools. We suggest that closer policy attention is needed for this rapidly proliferating approach to health research.

Over the past twenty-five years, international organizations have adopted human rights declarations in an attempt to address emerging ethical, legal and social concerns associated with genetic research and technologies. While these declarations point to important challenges and potential issues in genetics, the focus on genetics has been criticized for promoting the idea that there is something unique about our genes, and that therefore, they deserve special protections in our laws. It is also argued that this ‘genetic exceptionalism’ perspective has contributed to a reinvigoration of genetic essentialism and determinism. In this article, we add to this criticism by pointing out gaps and flaws in current gene-focused human rights declarations in light of recent developments in the field of epigenetics. First, we show that these documents do not provide guidance for a responsible governance of epigenetic data (e.g., privacy protection) and an ethical use of individual epigenetic information (e.g., nondiscrimination). This is particularly concerning given the interest recently demonstrated by insurance companies, forensic scientists and immigration agencies in using epigenetic clock technologies. Second, we argue that findings in epigenetics could contribute to the promotion of second- and third- generation human rights, i.e., respectively, economic, social and cultural rights, and solidarity rights. We conclude by calling for international bioethics and human rights organizations to pay greater attention to epigenetics and other postgenomic sciences in the coming years.

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.

Efforts to protect people’s privacy in a massive international cancer project offer lessons for data sharing.

The Canadian Genomics Partnership for Rare Diseases, spearheaded by Genome Canada, will integrate genome-wide sequencing to rare disease clinical care in Canada. Centralized and tiered models of data stewardship are proposed to ensure that the data generated can be shared for secondary clinical, research, and quality assurance purposes in compliance with ethics and law. The principal ethico-legal obligations of clinicians, researchers, and institutions are synthesized. Governance infrastructures such as registered access platforms, data access compliance offices, and Beacon systems are proposed as potential organizational and technical foundations of responsible rare disease data sharing. The appropriate delegation of responsibilities, the transparent communication of rights and duties, and the integration of data privacy safeguards into infrastructure design are proposed as the cornerstones of rare disease data stewardship.

Enabling genomic and biomedical data to be shared for secondary research purposes is not always straightforward for existing “legacy” data sets. Researchers may not know whether their data meet ethical and regulatory requirements for sharing. As a result, these data, collected using public funds and the good will and efforts of the donors and investigators, may not be used beyond their original purpose. Single-use plastics are now being banned in many countries; single-use research should be avoided if possible. This paper describes a filter developed through the driver projects of the Global Alliance for Genomics and Health that can be used by researchers to help them determine the extent of sharing possible for their legacy data and actions to be taken to enable further sharing.

Concerns about genetic discrimination (GD) often surface when discussing research and innovation in genetics. Over recent decades, countries around the world have attempted to address GD using various policy measures. In this article, we survey these approaches and provide a critical commentary on their advantages and disadvantages. Our examination begins with regions featuring extensive policy-making activities (North America and Europe), followed by regions with moderate policy-making activities (Australia, Asia, and South America) and regions with minimal policy-making activities (the Middle East and Africa). Our analysis then turns to emerging issues regarding genetic testing and GD, including the expansion of multiomics sciences and direct-to-consumer genetic tests outside the health context. We additionally survey the shortcomings of current normative approaches addressing GD. Finally, we conclude by highlighting the evolving nature of GD and the need for more innovative policy-making in this area.

Whole genome/exome sequencing (WGS/WES) has become widely adopted in research and, more recently, in clinical settings. Many hope that the information obtained from the interpretation of these data will have medical benefits for patients and—in some cases—also their biological relatives. Because of the manifold possibilities to reuse genomic data, enabling sequenced individuals to access their own raw (uninterpreted) genomic data is a highly debated issue. This paper reports some of the first empirical findings on personal genome access policies and practices. We interviewed 39 respondents, working at 33 institutions in 21 countries across Europe. These sequencing institutions generate massive amounts of WGS/WES data and represent varying organisational structures and operational models. Taken together, in total, these institutions have sequenced ∼317,259 genomes and exomes to date. Most of the sequencing institutions reported that they are able to store raw genomic data in compliance with various national regulations, although there was a lack of standardisation of storage formats. Interviewees from 12 of the 33 institutions included in our study reported that they had received requests for personal access to raw genomic data from sequenced individuals. In the absence of policies on how to process such requests, these were decided on an ad hoc basis; in the end, at least 28 requests were granted, while there were no reports of requests being rejected. Given the rights, interests, and liabilities at stake, it is essential that sequencing institutions adopt clear policies and processes for raw genomic data retention and personal access.

BackgroundResearch in the field of genomics and genetics has evolved in recent years and so has the demand of consumers who are increasingly interested in genomic prediction of diseases and various traits. The aim of this study is to identify genetic service delivery models, policies governing the use of genomics medicine, and measures to evaluate genetic services in the province of Quebec, Canada.MethodsAn ad hoc questionnaire was designed and administered online in 2017 to healthcare workers with good knowledge or experience in the provision of BReast CAncer genes 1 and 2 (BRCA1/2), Lynch syndrome, familial hypercholesterolemia, inherited thrombophilia genetic tests, engaged in policy planning or evaluation of genetic services. A quali-quantitative analysis of the survey results was performed.ResultsThirty professionals participated in the study. The delivery models are classified in five categories according to the leading role of healthcare professionals in patient care pathways: i) the geneticist model; ii) the primary care model; iii) the medical specialist model; iv) the population screening program model; and v) the direct-to-consumer model. Barriers to genetic services are the coverage of genetic tests by the publicly funded healthcare system, the availability of qualified personnel, and the number of genetic centers. Regulatory oversight concerning the provision of genetic services appears to be insufficient.ConclusionsIntegration between genetics and the overall healthcare system in Quebec is in an early phase. Current models of genetic services require good level of genetic knowledge by all medical specialists, collaboration among different healthcare personnel, and work redistribution. The proper implementation of genomics into healthcare can be achieved through education and training, proper regulatory oversight, genomic policies, and public awareness.

This policy tracker summarizes the key economic responses governments are taking to limit the human and economic impact of the COVID-19 pandemic

Palmira Granados Moreno, Yann Joly & Dylan Roskams-Edris Abstract Medical research in genomics is advancing at an accelerated pace. Every new discovery or invention creates a new and even more …

Recent advances in the biosciences invite reconsideration of fundamental legal concepts such as the definition of “human” , The law has always viewed living human beings—and the tissues, organs, and other body parts derived from them—as special and different from the nonliving, nonhuman. But bioscientific advances are nibbling away at classical legal boundaries that form the bedrock of the normative structures on which societies are based. Recent developments such as in human genetics, neuroscience, and cell and tissue research pose qualitatively different challenges than what has come before, seeming to blur legal distinctions between human beings and other living organisms, between living human beings and dead ones, and between human tissues and cells and nonhuman ones. Although cognizant of the important bioethical and philosophical debates surrounding the issues raised, we focus on how legal systems may respond to these bioscience challenges to traditional binary, legal classifications. Determining whether some “thing” is now some “one” carries with it profound implications for the rights and obligations the law recognizes for “humans.” Although it may be tempting to think that these new developments require us to reconsider the time-honored legal definitions of humans, living humans, or human tissue, we suggest that current legal dualisms can be applied in ways that provide adequate flexibility to allow weighing the many issues that surround developments in genetics, neurosciences, and cellular bioengineering and challenge how we legally define what is “human.”

In the past decade, there has been a surge in the number of sensitive human genomic and health datasets available to researchers via Data Access Agreements (DAAs) and managed by Data Access Committees (DACs). As this form of sharing increases, so do the challenges of achieving a reasonable level of data protection, particularly in the context of international data sharing. Here, we consider how excessive variation across DAAs can hinder these goals, and suggest a core set of clauses that could prove useful in future attempts to harmonize data governance.

Abstract Trust may be important in shaping public attitudes to genetics and intentions to participate in genomics research and big data initiatives. As such, we examined trust in data sharing among the general public. A cross-sectional online survey collected responses from representative publics in the USA, Canada, UK and Australia ( n  = 8967). Participants were most likely to trust their medical doctor and less likely to trust other entities named. Company researchers were least likely to be trusted. Low, Variable and High Trust classes were defined using latent class analysis. Members of the High Trust class were more likely to be under 50 years, male, with children, hold religious beliefs, have personal experience of genetics and be from the USA. They were most likely to be willing to donate their genomic and health data for clinical and research uses. The Low Trust class were less reassured than other respondents by laws preventing exploitation of donated information. Variation in trust, its relation to areas of concern about the use of genomic data and potential of legislation are considered. These findings have relevance for efforts to expand genomic medicine and data sharing beyond those with personal experience of genetics or research participants.

Public acceptance is critical for sharing of genomic data at scale. This paper examines how acceptance of data sharing pertains to the perceived similarities and differences between DNA and other forms of personal data. It explores the perceptions of representative publics from the USA, Canada, the UK and Australia (n = 8967) towards the donation of DNA and health data. Fifty-two percent of this public held ‘exceptionalist’ views about genetics (i.e., believed DNA is different or ‘special’ compared to other types of medical information). This group was more likely to be familiar with or have had personal experience with genomics and to perceive DNA information as having personal as well as clinical and scientific value. Those with personal experience with genetics and genetic exceptionalist views were nearly six times more likely to be willing to donate their anonymous DNA and medical information for research than other respondents. Perceived harms from re-identification did not appear to dissuade publics from being willing to participate in research. The interplay between exceptionalist views about genetics and the personal, scientific and clinical value attributed to data would be a valuable focus for future research.

Canada’s approach to human germline modification is generally conservative, at times unclear, and largely prohibitive from both a research and clinical perspective. To date, no research using human germline modification has been undertaken in Canada. This chapter provides an overview of the Canadian legal and policy landscape surrounding human germline modification. It will begin by laying the groundwork for the subsequent assessment of specific legal provisions and policies governing the modification of the human germline from basic research to clinical applications. Finally, it will reflect on the challenges and future possibilities for human germline modification in Canada.

In this reply, we wish to defend our original position and address several of the points raised by two excellent responses. The first response (De Miguel Beriain) questions the relevance of the notion of ‘serious’ within the context of human germline genome modification (HGGM). We argue that the ‘serious’ factor is relevant and that there is a need for medical and social lenses to delineate the limits of acceptability and initial permissible applications of HGGM. In this way, ‘serious’ acts as a starting point for further discussions and debates on the acceptability of the potential clinical translation of HGGM. Therefore, there is a pressing need to clarify its scope, from a regulatory perspective, so as to prevent individuals from using HGGM for non-therapeutic or enhancement purposes. The second response (Kalsi) criticizes the narrow interpretation of the objectivist approach and the apparent bias towards material innovations when discussing the right to benefit from scientific advancements. As an in-depth discussion of the objectivist and constructivist approaches was beyond the scope of our original paper, we chose to focus on one specific objectivist account, one which focuses on biological and scientific facts. We agree, however, with the critique that material innovations should not be the sole focus of the right to benefit from scientific advancements, which also incorporates freedom of scientific research and access to scientific knowledge scientific freedom and knowledge, including the influence of these on ethical thinking and cultures.

Over the past decade, smartphone technology has become increasingly sophisticated and ubiquitous. Modern smartphones, now owned by more than three quarters of Canadians and 94% of millennials, perform an array of functions that are potentially useful in the health care context, such as tracking fitness data, enabling health record sharing, and providing user-friendly platforms for disease management. Approximately half of smartphone users have downloaded at least one health app, and clinicians are increasingly using them in their practice. However, despite widespread use, there is little evidence that supports their safety and efficacy. Few apps have been independently evaluated and many lack basic patient protections such as privacy policies. In this context, the demand for the regulation of mobile health apps has increased. Against this backdrop, regulators, including Health Canada, have begun to propose regulating the use of smartphones in health care. In this viewpoint, we respond to Health Canada’s recent proposal to regulate smartphone use in Canada according to a risk-based model. We argue that although Health Canada’s recent proposed approach is promising, it may require complementary regulation and oversight.

Background: Advances in genomics and epidemiology can foster the implementation of a risk-based approach to current age-based breast cancer screening programs. This personalized approach would challenge the trajectory for women in the healthcare system by adding both a risk-assessment step (including a genomic test) and screening options. Objective: The aim of this study is to explore, from an organizational perspective, the acceptability of different proposals for each step of the trajectory for women in the healthcare system should a personalized approach be implemented in the province of Quebec. Methods: We interviewed 20 professional stakeholders who are either involved in the current breast cancer screening program in Quebec or who are likely to play a role in the future implementation of a personalized risk-based approach. Results and discussion: Preferences are split between proposals supporting self-management by the women themselves (e.g., solicitation through media campaign, self-collection of information and sample and results provided by letter) and proposals prioritizing more interaction between women and healthcare providers (e.g., solicitation by health professionals, collection of information and samples by a nurse and results provided by health professionals).

Approximately 80% of rare and often incurable and serious conditions affect newborns and children, and roughly half of all rare diseases are considered to have an onset in childhood. Somatic gene therapies are already in clinical trials for spinal muscular atrophy, beta thalassemia, and macular degeneration. If proven to be safe and effective, could heritable genome editing be seen as a form of preventive personalized medicine and as fostering the right to health of the child? The latest calls for global moratoria on clinical applications of heritable genome editing are troubling in that they may create an illusion of control over rogue science and stifle the necessary international debate surrounding an ethically responsible translational path forward. Children are people with distinct rights and interests. An arbitrary moratorium neither fosters their best interests or health nor respects their right to benefit from the advancements of science.

When writing about CRISPR and similar technologies, many bioethicists use science-fiction references to help readers picture the ramifications of germline gene editing. By a large margin, the most frequently referenced novel in this debate is Aldous Huxley's 1932 dystopia Brave New World. Despite its iconic status and effectiveness at communicating specific ethical issues, Brave New World provides relatively poor examples of interventions such as gene therapy or enhancement. In addition, the eugenic tropes that Huxley promotes in much of his work make Brave New World an uncomfortable choice for authors who oppose the use of CRISPR for illiberal purposes. Ethicists should consider bringing a wider variety of fiction references into the discourse on genome editing, especially stories that can complement Brave New World with insights about the ethical issues left undeveloped in Huxley's novel.

Epigenetics, defined as ‘the study of mitotically and/or meiotically heritable changes in gene function that cannot be explained by changes in DNA sequence’, has emerged as a promissory yet controversial field of scientific inquiry over the past decade. Scholars from many disciplines have formulated both optimistic and cautionary claims regarding its potential normative implications. This article provides a comprehensive review of the nascent literature at the crossroads of epigenetics, ethics, law and society. It describes nine emerging areas of discussion, relating to (1) the impact of epigenetics on the nature versus nurture dualism, (2) the potential resulting biologization of the social, (3) the meaning of epigenetics for public health, its potential influence on (4) reproduction and parenting, (5) political theory and (6) legal proceedings, and concerns regarding (7) stigmatization and discrimination, (8) privacy protection and (9) knowledge translation. While there is some degree of similarity between the nature and content of these areas and the abundant literature on ethical, legal and social issues in genetics, the potential implications of epigenetics ought not be conflated with the latter. Critical studies on epigenetics are emerging within a separate space of bioethical and biopolitical investigations and claims, with scholars from various epistemological standpoints utilizing distinct yet complementary analytical approaches.

Profoundly more data-intensive than conventional medicine, precision medicine’s distinctive informational needs present new challenges for healthcare management. Data protection and privacy law are key determinants in precision medicine’s future. This article examines legal and regulatory barriers to the incorporation of precision medicine into healthcare. Specific attention is paid to analyzing recent health privacy laws, court cases, and medical device regulations. Considering the challenges identified, recommendations and guidance are crafted for health leaders with reference to domestic and international initiatives.

Human germline genome editing may prove to be especially poignant for members of the rare disease community, many of whom are diagnosed with monogenic diseases. This community lacks broad representation in the literature surrounding genome editing, notably in Canada, yet is likely to be directly affected by eventual clinical applications of this technology. Although not generalizable, the literature does offer some commonalities regarding the experiences of rare disease patients. This manuscript seeks to contribute to the search for broader societal dialogue surrounding human germline genome editing by exploring some of those commonalities that comfort the notion that CRISPR may hold promise or be desirable for some members of this community. We first explore the legal and policy context surrounding germline genome editing, focusing closely on Canada, then provide an overview of the common challenges experienced by members of the rare disease community, and finally assess the opportunities of germline genome editing vis-à-vis rare disease as we advocate for the need to more actively engage with the community in our search for public engagement.

Rare Disease research has seen tremendous advancements over the last decades, with the development of new technologies, various global collaborative efforts and improved data sharing. To maximize the impact of and to further build on these developments, there is a need for model consent clauses for rare diseases research, in order to improve data interoperability, to meet the informational needs of participants, and to ensure proper ethical and legal use of data sources and participants’ overall protection.

Current advances in assisted reproductive technologies aim to promote the health and well-being of future children. They offer the possibility to select embryos with the greatest potential of being born healthy (eg, preimplantation genetic testing) and may someday correct faulty genes responsible for heritable diseases in the embryo (eg, human germline genome modification (HGGM)). Most laws and policy statements surrounding HGGM refer to the notion of ‘serious’ as a core criterion in determining what genetic diseases should be targeted by these technologies. Yet, this notion remains vague and poorly defined, rendering its application challenging and decision making subjective and arbitrary. By way of background, we begin by briefly presenting two conceptual approaches to ‘health’ and ‘disease’: objectivism (ie, based on biological facts) and constructivism (ie, based on human values). The basic challenge under both is sorting out whether and to what extent social and environmental factors have a role in helping to define what qualifies as a ‘serious’ disease beyond the medical criteria. We then focus on how a human rights framework (eg, right to science and right to the highest attainable health) could integrate the concepts of objectivism and constructivism so as to provide guidance for a more actionable consideration of ‘serious’. Ultimately, it could be argued that a human rights framework, by way of its legally binding nature and its globally accepted norms and values, provides a more universal foundation for discussions of the ethical, legal and social implications of emerging or disruptive technologies.

Over the past decade, researchers in epigenetics have developed testing methods to predict the chronological and biological age of individuals based on levels of DNA methylation at combinations of CpG sites in specific cell types. These epigenetic age and aging estimators, also referred to as ‘epigenetic clocks’, represent a promising avenue to better understand the biological pathways underlying the development of aging-associated disorders, and imagine biomedical and/or social interventions to prevent, reverse, or alleviate them. Epigenetic clock technologies aimed at testing for epigenetic age of different cell types also provide an opportunity to investigate how environmental stressors, social adversity, and unhealthy lifestyle can contribute to such disorders through epigenetic aging acceleration. In addition to their potential clinical and public health applications, epigenetic age and aging estimators may be used for non-medical purposes, such as insurance and forensic sciences. In this article, we present and discuss a set of potential ethical, legal, and social implications of non-medical uses of epigenetic clocks. We highlight concerns related to actuarial and moral fairness, free and informed consent, data governance and the protection of privacy, equity and non-discrimination principles, identification and surveillance, the moral liability of criminals, as well as scientific validity, test accuracy, and interpretation of test results. We argue that a human rights framework should guide further discussions about these important and timely questions.

Open science can significantly influence the development and translational process of precision medicine in Canada. Precision medicine presents a unique opportunity to improve disease prevention and healthcare, as well as to reduce health-related expenditures. However, the development of precision medicine also brings about economic challenges, such as costly development, high failure rates, and reduced market size in comparison with the traditional blockbuster drug development model. Open science, characterized by principles of open data sharing, fast dissemination of knowledge, cumulative research, and cooperation, presents a unique opportunity to address these economic challenges while also promoting the public good. The Centre of Genomics and Policy at McGill University organized a stakeholders’ workshop in Montreal in March 2018. The workshop entitled “Could Open be the Yellow Brick Road to Precision Medicine?” provided a forum for stakeholders to share experiences and identify common objectives, challenges, and needs to be addressed to promote open science initiatives in precision medicine. The rich presentations and exchanges that took place during the meeting resulted in this consensus paper containing key considerations for open science precision medicine in Canada. Stakeholders would benefit from addressing these considerations as to promote a more coherent and dynamic open science ecosystem for precision medicine.

The HUGO Committee on Ethics, Law and Society (CELS) undertook a Working Group exploration of the key ethical issues arising from genome sequencing in 2013. The Imagined Futures paper the group subsequently published proposed points to consider when applying genomic bioinformatics to data repositories used in genomic medicine and research (http://www.hugo-international.org/Resources/Documents/CELS_Article-ImaginedFutures_2014.pdf). Given the ever-increasing power to sequence the human genome rapidly and inexpensively—as well as trends toward “Big Data” and “Open Science”—we take this opportunity to update and refine the key findings of that paper.

As epigenetic studies become more common and lead to new insights into health and disease, the return of individual epigenetic results to research participants, in particular in large-scale epigenomic studies, will be of growing importance. Members of the International Human Epigenome Consortium (IHEC) Bioethics Workgroup considered the potential ethical, legal, and social issues (ELSI) involved in returning epigenetic research results and incidental findings in order to produce a set of ‘Points-to-consider’ (P-t-C) for the epigenetics research community. These P-t-C draw on existing guidance on the return of genetic research results, while also integrating the IHEC Bioethics Workgroup’s ELSI research on and discussion of the issues associated with epigenetic data as well as the experience of a return of results pilot study by the Personal Genome Project UK (PGP-UK). Major challenges include how to determine the clinical validity and actionability of epigenetic results, and considerations related to environmental exposures and epigenetic marks, including circumstances warranting the sharing of results with family members and third parties. Interdisciplinary collaboration and good public communication regarding epigenetic risk will be important to advance the return of results framework for epigenetic science.

In this commentary, we critically review the Quebec Court of Appeal’s reference decision to the effect that the Genetic Non-Discrimination Act (GNDA) is unconstitutional. In sum, the court held that the federal government exceeded its criminal law power through the GNDA, as the Act did not have a valid criminal law purpose. The decision was met with opposition, as advocacy groups for Canadians suffering from genetic diseases or genetic predispositions viewed the GNDA as a step in the right direction and were hopeful that it would offer protection from genetic discrimination. In closing, we argue that the consequences of the Court of Appeal’s opinion will be less dire than anticipated by some advocacy groups. In fact, we suggest that this decision brings about a unique opportunity for progress, where stakeholders can engage the public and policymakers in a forward- looking debate on the use of genetic information. , Dans ce commentaire, nous examinons de façon critique la décision de renvoi de la Cour d’appel du Québec à l’effet que la Loi sur la non-discrimination génétique (LNDA) est inconstitutionnelle. En résumé, la Cour a conclu que le gouvernement fédéral a outrepassé ses pouvoirs en matière de droit pénal par l’entremise de la LNDA, car celle-ci n’avait pas d’objet valide en droit pénal. Cette décision a fait l’objet d’une opposition car les groupes de défense des intérêts des Canadiens souffrant de maladies génétiques ou de prédispositions génétiques considéraient la LNDA comme un pas dans la bonne direction et espéraient qu’elle offrirait une protection contre la discrimination génétique. En terminant, nous soutenons que les conséquences de l’avis de la Cour d’appel seront moins graves que ne le prévoient certains groupes de défense. En fait, nous suggérons que cette décision offre une occasion unique de progrès, où les intervenants peuvent faire participer le public et les décideurs à un débat tourné vers l’avenir sur l’utilisation de l’information génétique.

Deux juristes se penchent sur la récente décision de la Cour d'Appel relativement à la Loi sur la Non-Discrimination Génétique (LNDG).

Next week, the federal government will table its last budget before the upcoming election. It will likely be filled with initiatives that appeal directly to Canadian voters. I hope Prime Minister Justin Trudeau and his cabinet will also be considering investments that result in longer-term societal benefits. More specifically, a provision of much needed support […]

This paper, examines the impact of changing evidentiary standards by the FDA on the conduct of clinical trials, drug approvals and prescriber duties, and patients, as well as the need for data sharing. Shifting focus to molecular subtypes of low frequency and allowing for the grouping for trial eligibility has implications not only for pharmaceutical industry sponsors, but also for multiple actors in the drug development process to advance the improvement and availability of safe and effective targeted treatments for rare diseases, as well as common diseases due to rare mutations.

Drawing on a landscape analysis of existing data-sharing initiatives, in-depth interviews with expert stakeholders, and public deliberations with community advisory panels across the U.S., we describe features of the evolving medical information commons (MIC). We identify participant-centricity and trustworthiness as the most important features of an MIC and discuss the implications for those seeking to create a sustainable, useful, and widely available collection of linked resources for research and other purposes.

Younger women at higher-than-population-average risk for breast cancer may benefit from starting screening earlier than presently recommended by the guidelines. The Personalized Risk Stratification for Prevention and Early Detection of Breast Cancer (PERSPECTIVE) approach aims to improve the prevention of breast cancer through differential screening recommendations based on a personal risk estimate. In our study, we used deliberative stakeholder consultations to engage health professionals in an in-depth dialog to explore the feasibility of the proposed implementation strategies for this new personalized breast cancer screening approach.

Efforts are underway to harmonise the return of individual results and incidental findings from whole genome sequencing (WGS) across research contexts and countries. We reviewed international, regional and national laws and policies applying to return across 20 countries to identify areas of convergence and divergence. Discrepancies between laws and policies are most problematic where they cannot be reconciled through harmonisation of project-level governance. Rules for the return of results apply at different levels in different jurisdictions (e.g., human subjects research, biobanks, clinical trials, genomic sequencing, and genetic/personal data), complicating comparison. A particular concern for harmonisation are the (often contradictory) rules about when results must, should, may, or must not be returned. Adding confusion are different thresholds for utility (medical, familial, reproductive, and/or personal). The importance of respecting individual choices to know or not know is widely recognised, though some norms emphasise respect for personal preferences. Another troubling observation is that requirements for data quality, variant assessment, and the effective communication of results are evolving in uneven ways. There is a growing gap between researchers with the expertise, infrastructure, and resources to meet these requirements and those without, threatening international collaboration. Best practices for the return of individual genomic results are sorely needed to inform not only the ethical return of results, but also future legislative and policy efforts.

Open science has recently gained traction as establishment institutions have come on-side and thrown their weight behind the movement and initiatives aimed at creation of information commons. At the same time, the movement's traditional insistence on unrestricted dissemination and reuse of all information of scientific value has been challenged by the movement to strengthen protection of personal data. This article assesses tensions between open science and data protection, with a focus on the GDPR.

Our understanding of the clinical significance of genomic data is rapidly evolving. The meaning of a patient’s test results can therefore change over time. Reanalysis of genomic data over time and patient recontact offer an opportunity to improve patient health. But are physicians legally responsible to do so? Professional associations worldwide are outlining best practices for genetic recontact. To inform Canadian guidelines and courts faced with this issue, we review Canadian case law to determine if there is a likely doctrinal basis for judicial recognition of a duty to recontact in genetics. Foreign guidelines or malpractice case law may not adequately reflect the peculiarities of Canada’s diverse legal and public health systems. A threshold consideration is the duration of the physician-patient relationship, seeing as physicians do not generally owe legal duties to former patients. This legal relationship endures according to the need for continued care as well as the subjective perspectives of both physician and patient. Satisfying these criteria in genetics can be difficult because of interpretative uncertainty or the absence of definitive intervention. Moreover, coordination of genetic analysis, communication, and follow-up care between healthcare professionals is complex, leading to problems of incomplete hand-off between laboratories, specialists, and primary care providers. The key challenge for plaintiffs will be to establish fault, that is, breach of a duty. Physicians in Canada traditionally have duties to diagnose, inform, follow-up and of confidentiality. We conclude that a legal duty of genetic recontact is only likely in specific circumstances where physicians acquire updated genetic information of clear health significance. This remains unlikely unless health systems or laboratories commit to systemic and adaptive reanalysis. This may change with the confluence of whole genome testing and advanced health information technologies (HIT). Whole genome sequences include millions of individual genetic variants and in turn, millions of opportunities for adaptive reinterpretation. HIT enables data sharing between laboratories, automated reanalysis of genomic test results, and new lines of communication with physicians and patients. Fundamentally, it is only health systems or institutions that can provide the infrastructure needed to adapt patient care in step with an evolving genetic knowledgebase.

La consultation vidéo est de plus en plus utilisée pour prodiguer des services de télésanté aux patients. Or, si l’offre en télésanté augmente, les normes juridiques et déontologiques qui ont précisément pour objet de l’encadrer se font rares. La difficulté liée à la mise en évidence des normes applicables pourrait avoir été un frein à la mise en oeuvre des services de télésanté. Nous avons mené une analyse qui permet de dégager certains standards applicables à une consultation vidéo. D’abord, nous expliquons la similarité des obligations pour les professionnels entre la pratique en présence et la pratique par télésanté. Ensuite, nous précisons les normes applicables dans le cas de sept thèmes qui soulèvent des enjeux particuliers en matière de télésanté, soit le lieu où les services sont rendus, la confidentialité, le consentement, la pertinence de la rencontre en personne, les compétences et les habiletés technologiques, le dossier médical ainsi que la continuité des services.

As scientific understanding of the heritable aspects of cancer deepens, the need to effectively communicate genetic information within the families of cancer patients becomes more acute. In the palliative care context, the question of when and how to disclose a patient’s genetic information raises a host of ethical, legal, and social issues, including the challenges of communicating during the end-of-life stage and complex familial and cultural dynamics. In this paper, the authors outline the legal components of these issues in three civil law jurisdictions with similarly comprehensive approaches to healthcare and palliative care - Quebec, Belgium, and France - and provide insights from bioethics literature and normative documents on the disclosure of genetic information at the end of life. From this research, the authors propose a strategy for palliative care providers who are considering available options to communicate hereditary health information.

American Indians and Alaska Natives have long held a state-conferred right to health, yet Indigenous communities across the United States continue to experience significant health and health care disparities. In this paper we posit two contributing factors: socialization for scarcity in tribal health care, and a slowness among health workers and allied health and social scientists to make explicit and convincing linkages between social determinants of health and human rights. We then summarize one attempt to align tribal health care delivery in the Alaskan Arctic with a rights-based approach, highlighting both the role of social and structural determinants as causes of health disparities and the role of social and structural interventions in local efforts to chart a future of equal health for our home.

L’épigénétique est un champ d’études qui s’intéresse aux modifications biochimiques et aux changements dans la structure tridimensionnelle (3D) de l’ADN ayant pour effet de contraindre ou de faciliter la lecture et l’expression des gènes. Au cours des dix dernières années, l’épigénétique a attiré l’attention d’un nombre croissant de chercheurs en sciences sociales, puisqu’elle semble venir confirmer, cette fois sur le plan moléculaire, le rôle déterminant de l’environnement développemental (physico-chimique et psychosocial) des personnes dans la configuration de leur individualité biologique et dans la programmation de leur santé future. Cet article se penche sur les implications épistémologiques potentielles de l’épigénétique. Nous distinguons et décrivons trois perspectives socio-anthropologiques complémentaires, adoptées par différents auteurs, sur le rapprochement des concepts de « nature » et de « culture » par l’épigénétique : la socialisation du biologique, la biologisation du social et la superposition nature-culture. , Epigenetics is a field of study that focuses on biochemical modifications and changes in the tridimensional (3D) structure of DNA that have the effect of constraining or facilitating the reading and expression of genes. Over the last ten years, epigenetics has captured the attention of several social scientists since it appears to confirm, this time at the molecular level, the determining role of the developing environment of people in configurating their biological individuality and programming their future health. This article discusses the potential epistemological implications of epigenetics. It distinguishes and describes three complementary socio-anthropological perspectives, taken by different authors, on the rapprochement of the concepts “nature” and “nurture” by epigenetics: the socialization of the biological, the biologization of the social, and the superimposition nature-nurture.

Stem cells may not systematically obey traditional Phase I–IV clinical translation models. In response, various actors have suggested that stem cell-based medical innovation models could catalyze translation instead. Accordingly, calls were made to adopt more permissive approaches to stem cell translation. Yet, the Phase I–IV paradigm remains the standard within the scientific community. This article seeks to advance the stalemated discussions by proposing an alternative model for consideration. In it, we argue that a stem cell-based learning health system may be able to reconcile these two models. Centered on the acceleration of evidence and knowledge flow, a stem cell-based learning health system could maximize patient retention and data follow-up, thereby promoting inclusive system learning and improvement.

Over its 30 or so years of existence, the genomic commons—the worldwide collection of publicly accessible repositories of human and nonhuman genomic data—has enjoyed remarkable, perhaps unprecedented, success. Thanks to the rapid public data release policies initiated by the Human Genome Project, free access to a vast array of scientific data is now the norm, not only in genomics, but in scientific disciplines of all descriptions. And far from being a monolithic creation of bureaucratic fiat, the genomic commons is an exemplar of polycentric, multistakeholder governance. But like all dynamic and rapidly evolving systems, the genomic commons is not without its challenges. Issues involving scientific priority, intellectual property, individual privacy, and informed consent, in an environment of data sets of exponentially expanding size and complexity, must be addressed in the near term. In this review, we describe the characteristics and unique history of the genomic commons, then address some of the trends, challenges, and opportunities that we envision for this valuable public resource in the years to come.

The evolution of genomic research and its integration into clinical practice, as they become international—even global—endeavors, has brought us to a place where scientists and clinicians may now only ignore the rules governing international data sharing at their own peril. Open data policies, on the one hand, increasingly require custodians of others’ genomic data to make it as widely available as feasible, including to researchers in other countries. Data protection law, on the other, has become a significant hurdle to the sharing of personal data across jurisdictional borders. The space between these two competing duties is narrowing. In contrast with the other texts in this volume, which explore the present and future of data sharing and data protection, this article’s focus is on the past. It centres on the historical development of the data protection rules regarding the international transfer of personal data up to the present. The article’s aim is to bring into focus the underlying objectives that have influenced and that will continue to influence the way that data protection rules are applied to the fields of genomics and health, as well as future developments in data protection generally. The first part of this article describes the development of international data-sharing data protection rules since 1970. The second considers difficulties in applying general data protection rules to the specific context of genomics and health. The third and final part compares the options available to comply with the international transfer restrictions set out in the standard-setting EU General Data Protection Regulation from a genomics perspective.

Our international study, ‘Your DNA, Your Say’, uses film and an online cross-sectional survey to gather public attitudes toward the donation, access and sharing of DNA information. We describe the methodological approach used to create an engaging and bespoke survey, suitable for translation into many different languages. We address some of the particular challenges in designing a survey on the subject of genomics. In order to understand the significance of a genomic result, researchers and clinicians alike use external databases containing DNA and medical information from thousands of people. We ask how publics would like their ‘anonymous’ data to be used (or not to be used) and whether they are concerned by the potential risks of reidentification; the results will be used to inform policy.

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Through the widespread availability of location-identifying devices, geolocalisation could potentially be used to place athletes during out-of-competition testing. In light of this debate, the WADA Ethics Panel formulated the following questions: (1) should WADA and/or other sponsors consider funding such geolocalisation research projects?, (2) if successful, could they be proposed to athletes as a complementary device to Anti-Doping Administration and Management System to help geolocalisation and reduce the risk of missed tests? and (3) should such devices be offered on a voluntary basis, or is it conceivable that they would be made mandatory for all athletes in registered testing pools? In this position paper, the WADA Ethics Panel concludes that the use of geolocalisation could be useful in a research setting with the goal of understanding associations between genotype, phenotype and environment; however, it recognises that the use of geolocalisation as part of or as replacement of whereabouts rules is replete with ethical concerns. While benefits remain largely hypothetical and minimal, the potential invasion of privacy and the data security threats are real. Considering the impact on privacy, data security issues, the societal ramifications of offering such services and various pragmatic considerations, the WADA Ethics Panel concludes that at this time, the use of geolocalisation should neither be mandated as a tool for disclosing whereabouts nor implemented on a voluntary basis.

This paper presents an in-depth qualitative analysis of the impact of diagnosis on the lives of rare disease (RD) patients. While diagnosis may be described as a watershed step for RD patients, no extensive account of nonmedical outcomes following a RD diagnosis exists within the literature. This study aims to fill this knowledge gap through an analysis of the impact of diagnosis on the lives of RD patients according to their personal experiences. Qualitative research was conducted in three provinces across Canada, with a total of 23 participants, both adult and parents of children with RD, diagnosed and not yet diagnosed. A thematic approach guided the analysis of the transcripts. The results reveal that the impacts of a RD diagnosis for both adults and paediatric patients are multifold, ranging from social to personal and medical impacts (including cases where etiological treatments for the diseases are non-existent). Furthermore, the results shed light on distinct factors that affect the scope of impacts of a diagnosis.

Les professionnels de la santé affectés aux soins critiques (urgence, soins intensifs, réanimation et soins coronariens) sont confrontés au quotidien à des situations particulièrement éprouvantes sur le plan émotionnel. Leurs conditions de travail difficiles peuvent devenir anxiogènes, se répercuter sur leur condition physique et/ou psychologique, diminuer leur performance et augmenter leur taux d’absentéisme au travail. Pour faire face à ce contexte stressant et parfois même déprimant, certains professionnels ont recours à l’humour macabre (ou « gallows humour »), une forme d’humour noir à connotation morbide, dont le contenu est susceptible de choquer certaines personnes. Bien que très répandue, l’utilisation de l’humour macabre en soins critiques est extrêmement controversée et la plupart du temps réprimandée par les ordres professionnels. Prenant appui sur les codes déontologiques qui les régissent, les ordres professionnels supposent que l’humour macabre enfreint les devoirs et les responsabilités de leurs membres envers leurs patients, rejetant alors son utilisation d’emblée. Dans cet article, nous contestons le rejet catégorique de l’humour macabre en soins critiques. Nous adoptons une perspective conséquentialiste, axée sur l’étude de la littérature scientifique portant sur les bienfaits de l’utilisation de l’humour en milieu de travail, pour défendre son acceptabilité éthique. En permettant d’être mieux disposés à prodiguer des soins malgré les événements tragiques vécus par les professionnels, nous verrons comment l’utilisation de l’humour macabre peut ultimement avoir des retombées positives sur les patients. L’éthique conséquentialiste n’est pas intéressée seulement par la maximisation des bienfaits de l’humour macabre, mais également par la réduction des risques de préjudices à autrui associés à son utilisation. Ce critère important nous conduira donc à définir les termes et à proposer certaines conditions devant être respectées pour une utilisation éthique de ce mécanisme de défense important par les professionnels de la santé en soins critiques. , Health care professionals assigned to critical care (emergency, intensive care, reanimation) are confronted on a daily basis with particularly trying situations. Their hard work conditions can become anxiety-provoking, affect their physical and/or psychological condition, decrease their performance and increase their absenteeism rate at work. To face this particularly stressful and sometimes depressing context, some professionals fall back on “gallows humour”, a sort of black humour with a morbid overtone, which is likely to shock certain people. Although gallows humour is very widespread, its use in critical care is extremely controversial and most of the time reprimanded by professional orders. Based on the codes of ethics that govern them, professional orders assume that gallows humour violates the duties and responsibilities of their members towards their patients, rejecting its use straightaway. In this article, we contest the categorical rejection of gallows humour in critical care. We adopt a consequentialist perspective based on the study of scientific literature on the benefits of using humour in the workplace, to defend its ethical acceptability. By enabling us to be better prepared to provide care despite the tragic events experienced by professionals, we will see how the use of gallows humour can ultimately have a positive effect on patients. A consequentialist ethics is not only interested in maximizing the benefits of gallows humour but also in reducing the risk of harm to others related to its use. This important criterion will therefore lead us to define the terms and suggest certain conditions that must be respected for an ethical use of this important defense mechanism by health care professionals in critical care.

Le traitement et l'étude du cancer nécessitent de collecter et conserver des tissus malades et ainsi constituer des collections qui serviront d'abord au patient lui-même, ensuite éventuellement à la recherche. La mise à disposition, à destination des chercheurs, des échantillons et des données relatives au patient, constitue un maillon indispensable à l'avancée des protocoles de soin, en permettant particulièrement de tester des biomarqueurs pour la prévention et le diagnostic. Cet ouvrage analyse la manière dont est valorisée la ressource essentielle pour la recherche que constituent les éléments biologiques humains, principalement les tissus tumoraux et les données personnelles associées. Dès l'origine, les collections structurées de tumeurs (« tumorothèques ») ont occupé une place importante parmi les biobanques. Depuis une dizaine d'années, ces collections font l'objet d'un encadrement législatif qui protège différents intérêts, mais qui détermine aussi le moyen d'un standard commun de conservation et de circulation. C'est pourquoi la question redoutable de la « valorisation » des collections et, concrètement, de leur régulation ou de leur gouvernance est abordée du point de vue du droit, de l'économie et de la sociologie. L'ouvrage s'organise autour de trois moments : d'abord, une description (sous forme de décomposition-reconstruction) des échantillons et des collections, puis l'étude des intérêts en jeu pour ces collections (économiques et sociétaux) ; enfin, l'examen des différents moyens possibles pour mettre à disposition, patrimonialiser et valoriser ces collections de ressources biologiques humaines

The participation of persons with dementia in health research is necessary to evaluate the safety and efficacy of ne…

The collapse of confidence in anonymization (sometimes also known as de-identification) as a robust approach for preserving the privacy of personal data has incited an outpouring of new approaches that aim to fill the resulting trifecta of technical, organizational, and regulatory privacy gaps left in its wake. In the latter category, and in large part due to the growth of Big Data–driven biomedical research, falls a growing chorus of calls for criminal and penal offences to sanction wrongful re-identification of “anonymized” data. This chorus cuts across the fault lines of polarized privacy law scholarship that at times seems to advocate privacy protection at the expense of Big Data research or vice versa. Focusing on Big Data in the context of biomedicine, this article surveys the approaches that criminal or penal law might take toward wrongful re-identification of health data. It contextualizes the strategies within their respective legal regimes as well as in relation to emerging privacy debates focusing on personal data use and data linkage and assesses the relative merit of criminalization. We conclude that this approach suffers from several flaws and that alternative social and legal strategies to deter wrongful re-identification may be preferable.

The human genome can reveal sensitive information and is potentially re-identifiable, which raises privacy and security concerns about sharing such data on wide scales. In 2016, we organized the third Critical Assessment of Data Privacy and Protection competition as a community effort to bring together biomedical informaticists, computer privacy and security researchers, and scholars in ethical, legal, and social implications (ELSI) to assess the latest advances on privacy-preserving techniques for protecting human genomic data. Teams were asked to develop novel protection methods for emerging genome privacy challenges in three scenarios: Track (1) data sharing through the Beacon service of the Global Alliance for Genomics and Health. Track (2) collaborative discovery of similar genomes between two institutions; and Track (3) data outsourcing to public cloud services. The latter two tracks represent continuing themes from our 2015 competition, while the former was new and a response to a recently established vulnerability. The winning strategy for Track 1 mitigated the privacy risk by hiding approximately 11% of the variation in the database while permitting around 160,000 queries, a significant improvement over the baseline. The winning strategies in Tracks 2 and 3 showed significant progress over the previous competition by achieving multiple orders of magnitude performance improvement in terms of computational runtime and memory requirements. The outcomes suggest that applying highly optimized privacy-preserving and secure computation techniques to safeguard genomic data sharing and analysis is useful. However, the results also indicate that further efforts are needed to refine these techniques into practical solutions.

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.

The use of assisted reproductive technologies (ART) has increased significantly, allowing many coping with infertility to conceive. However, an emerging body of evidence suggests that ART could carry epigenetic risks for those conceived through the use of these technologies. In accordance with the Developmental Origins of Health and Disease hypothesis, ART could increase the risk of developing late-onset diseases through epigenetic mechanisms, as superovulation, fertilization methods and embryo culture could impair the embryo’s epigenetic reprogramming. Such epigenetic risks raise ethical issues for all stakeholders: prospective parents and children, health professionals and society. This paper focuses on ethical issues raised by the consideration of these risks when using ART. We apply two key ethical principles of North American bioethics (respect for autonomy and non-maleficence) and suggest that an ethical tension may emerge from conflicting duties to promote the reproductive autonomy of prospective parents on one hand, and to minimize risks to prospective children on the other. We argue that this tension is inherent to the entire enterprise of ART and thus cannot be addressed by individual clinicians in individual cases. We also consider the implications of the ‘non-identity problem’ in this context. We call for additional research that would allow a more robust evidence base for policy. We also call upon professional societies to provide clinicians with guidelines and educational resources to facilitate the communication of epigenetic risks associated with ART to patients, taking into consideration the challenges of communicating risk information whose validity is still uncertain.

Regenerative medicine has attracted the interest of scientists, physicians, and patient communities, and as well as policy-makers and the broader public given related ethical, legal, and social implications. Here we examine past initiatives in the ethical, legal and social implications arena in regenerative medicine, and offer our views on actionable priorities for the future in six key areas: capacity building, policy, engagement with industry, resaerch ethics, communication, and community building.

In the past several years, rare disease consortia have embarked on the discovery of disease-causing genes for Mendelian diseases using next generation sequencing approaches. Despite the success of these large-scale initiatives, many diseases still have no identified genetic cause. The Rare Disease Collaboration for Autosomal Loci (RaDiCAL) studies the rarest diseases, where occasionally only a single proband is available to identify putative disease-causing genes. This article reviews how “RaDiCAL” addressed some of the challenges in generating informed consent documents for international participants and considers the emerging topic of the “right not to know” in study design.

Provision of a molecularly confirmed diagnosis in a timely manner for children and adults with rare genetic diseases shortens their ‘‘diagnostic odyssey,’’ improves disease management, and fosters genetic counseling with respect to recurrence risks while assuring reproductive choices. In a general clinical genetics setting, the current diagnostic rate is approximately 50%, but for those who do not receive a molecular diagnosis after the initial genetics evaluation, that rate is much lower. Diagnostic success for these more challenging affected individuals depends to a large extent on progress in the discovery of genes associated with, and mechanisms underlying, rare diseases. Thus, continued research is required for moving toward a more complete catalog of disease-related genes and variants. The International Rare Diseases Research Consortium (IRDiRC) was established in 2011 to bring together researchers and organizations invested in rare disease research to develop a means of achieving molecular diagnosis for all rare diseases. Here, we review the current and future bottlenecks to gene discovery and suggest strategies for enabling progress in this regard. Each successful discovery will define potential diagnostic, preventive, and therapeutic opportunities for the corresponding rare disease, enabling precision medicine for this patient population.

Recessive mutations in the ubiquitously expressed POLR3A gene cause one of the most frequent forms of childhood-onset hypomyelinating leukodystrophy (HLD): POLR3-HLD. POLR3A encodes the largest subunit of RNA Polymerase III (Pol III), which is responsible for the transcription of transfer RNAs (tRNAs) and a large array of other small non-coding RNAs. In order to study the central nervous system pathophysiology of the disease, we introduced the French Canadian founder Polr3a mutation c.2015G > A (p.G672E) in mice, generating homozygous knock-in (KI/KI) as well as compound heterozygous mice for one Polr3a KI and one null allele (KI/KO). Both KI/KI and KI/KO mice are viable and are able to reproduce. To establish if they manifest a motor phenotype, WT, KI/KI and KI/KO mice were submitted to a battery of behavioral tests over one year. The KI/KI and KI/KO mice have overall normal balance, muscle strength and general locomotion. Cerebral and cerebellar Luxol Fast Blue staining and measurement of levels of myelin proteins showed no significant differences between the three groups, suggesting that myelination is not overtly impaired in Polr3a KI/KI and KI/KO mice. Finally, expression levels of several Pol III transcripts in the brain showed no statistically significant differences. We conclude that the first transgenic mice with a leukodystrophy-causing Polr3a mutation do not recapitulate the childhood-onset HLD observed in the majority of human patients with POLR3A mutations, and provide essential information to guide selection of Polr3a mutations for developing future mouse models of the disease.

Yuen et al. developed a cloud-based database with 5,205 whole genomes from families with autism spectrum disorder (ASD). They identified 18 new candidate ASD-risk genes and approximately 100 risk genes and copy-number loci, which account for 11% of the cases. They also found that individuals bearing mutations in ASD-risk genes had lower adaptive ability.

The use of genome-wide (whole genome or exome) sequencing for population-based newborn screening presents an opportunity to detect and treat or prevent many more serious early-onset health conditions than is possible today.

Samples and data from population studies are stored for long periods of time, and can be accessed by national and international researchers to further their own studies and contribute to their understanding of the impact of a number of factors (e.g., environment, lifestyle) on common diseases and their progression. Part 2 of this Chapter discusses the nature of the researcher’s duty to inform, which is the result of an individualistic conception of autonomy. Parts 3 and 4 review this restrictive conception of autonomy, and concludes that it is rooted in a unilateral approach that is incongruous with the nature of biobank genomic research. Finally, Part 5 proposes that autonomy be complemented by the principle of reciprocity, which would not only create a fair and balanced relationship between researchers and participants, but would also recognize the public as a key contributor to genomic research.

In recent years, risk stratification has sparked interest as an innovative approach to disease screening and prevention. The approach effectively personalizes individual risk, opening the way to screening and prevention interventions that are adapted to subpopulations. The international PERSPECTIVE project, which is developing risk stratification for breast cancer, aims to support the integration of its screening approach into clinical practice through comprehensive tool-building. Policies and guidelines for risk stratification—unlike those for population screening programs, which are currently well regulated—are still under development. Indeed, the development of guidelines for risk stratification reflects the translational aspects of PERSPECTIVE. Here, we describe the risk stratification process that was devised in the context of PERSPECTIVE, and we then explain the consensus-based method used to develop recommendations for breast cancer screening and prevention in a risk-stratification approach. Lastly, we discuss how the recommendations might affect current screening policies.

Facilitating the responsible access to genomic research data is an emerging ethical and scientific imperative. Data Access Committees (DACs) assess the ethical footing and scientific feasibility of the data access requests and evaluate the qualification of applicants to ensure they are bona fide researchers. Through semi-structured interviews, we explored the opinions and experiences of 20 DAC members and experts concerning the users’ qualification criteria and mechanisms to hold users accountable. According to our respondents, such evaluation is necessary to ensure applicants are trustworthy, meet a certain level of expertise or experience and are aware of the rules and the associated concerns with genomic data sharing. The respondents noted, however, that the qualification criteria are fragmented or are poorly delineated at times. Thus, developing qualification criteria seems vital for an objective, fair and responsible access procedure. Similarly, the access review will benefit from using common ways of verifying the users’ affiliations. Furthermore, some DAC members expressed concern over the uncertain oversight of downstream data use, in particular where data are shared across borders. DAC members and experts did not consider current sanctions and enforcement procedures to be crystal clear. Therefore, data sharing policies should address this gap by establishing proportionate sanctions both against data producers and data users’ non-compliance. Users’ home institutes will need to have an active role in keeping oversight on the downstream data uses, considering their ultimate responsibility if wrongdoings happen.

Because children are presumed to have insufficient cognitive ability to consent to participate in research, pediatric research raises particular ethical and legal issues. For children who have not reached the age of consent stipulated by law or policy, parents (or legal guardians) must authorize their participation. This paper explores the issue of whether, to satisfy the ethical and legal norms of consent for research, participants in pediatric studies who attain the age of majority after their parents or guardians enrolled them in a study should be “recontacted” to obtain their consent to remain in the study. Using three different contexts (longitudinal studies, clinical trials, and newborn screening), we argue that distinctions should be made between the risks and benefits involved in recontacting for consent before determining the potential duties of researchers. An obligation to recontact should always be balanced with the feasibility and cost of such efforts in each particular research context and with consideration for the existence or lack of an ongoing relationship with the participant.

Aim: Primary care physicians will play a central role in the successful implementation of pharmacogenomics (PGx); however, important challenges remain. We explored the perspectives of stakeholders on key challenges of the PGx translation process in primary care using deliberative consultations. Methods: Primary care physicians, patients and policy-makers attended deliberations, where they discussed four ethical questions raised by PGx research and implementation in the primary care context. Results: Stakeholders voiced skepticism regarding PGx funding, commercialization, regulation, maintenance of an equal access healthcare system and restructuring of health research incentives and priorities in the public sector. Conclusion: Deliberants developed governing principles for a PGx-specific charter of ethics, aiming to protect the interests of patients, and outlined recommendations for the future of PGx in primary care.

Background Numerous studies report an association between social support and protection from depression, but no systematic review or meta-analysis exists on this topic. Aims To review systematically the characteristics of social support (types and source) associated with protection from depression across life periods (childhood and adolescence; adulthood; older age) and by study design (cross-sectional v . cohort studies). Method A systematic literature search conducted in February 2015 yielded 100 eligible studies. Study quality was assessed using a critical appraisal checklist, followed by meta-analyses. Results Sources of support varied across life periods, with parental support being most important among children and adolescents, whereas adults and older adults relied more on spouses, followed by family and then friends. Significant heterogeneity in social support measurement was noted. Effects were weaker in both magnitude and significance in cohort studies. Conclusions Knowledge gaps remain due to social support measurement heterogeneity and to evidence of reverse causality bias.

In setting up a data access policy to share controlled access data from the McGill Epigenomics Mapping Centre (EMC), an International Human Epigenome Consortium (IHEC) partner project, we encountered ethical and legal challenges that are likely to be relevant to other researchers sharing data, especially from Canadian projects. We discuss our solutions to the following data-sharing challenges, based on comparative legal and policy analysis: (1) providing access to data to a growing number of researchers; (2) maintaining Canadian privacy standards while sharing controlled access data internationally; (3) freedom of information requests; and (4) providing more incentives for researchers to share pre-publication data.

Objectif : La stratification en catégories de risque, selon des facteurs génétiques et cliniques, permettra bientôt d’améliorer les programmes de dépistage du cancer du sein. Nous avons voulu comprendre l’influence des dimensions organisationnelles sur l’éventuelle implantation de cette approche au Québec. Méthodes : Des entretiens semi-dirigés ont été effectués auprès de 16 décideurs et gestionnaires du programme québécois de dépistage du cancer du sein (PQDCS). Un cadre d’analyse institutionnel a été retenu pour analyser les données. Résultats : L’analyse thématique des entretiens a permis de dégager un consensus sur la nécessité d’implanter une approche davantage personnalisée, fondée sur la stratification du risque, en complémentarité avec le PQDCS. Plusieurs interviewés se sont montrés préoccupés par les besoins en termes de ressources humaines ainsi que par le rôle que médecins et infirmières pourraient être appelés à jouer. L’adaptation des outils de communication aux caractéristiques des populations locales, l’équité interrégionale dans l’accès aux services, et les effets sur le taux de participation au programme organisé en place (PQDCS) ont aussi été soulevés par les interviewés. Conclusion : Notre analyse fait ressortir l’importance du contexte organisationnel du système de soins où s’implantera l’approche par stratification du risque. La disponibilité de ressources humaines formées adéquatement, l’adaptation des outils aux réalités sociodémographiques, et la compatibilité avec les mesures de la performance constituent des éléments-clés à considérer.

Recent projects conducted by the International Cancer Genome Consortium (ICGC) have raised the important issue of distinguishing quality assurance (QA) activities from research in the context of genomics. Research was historically defined as a systematic effort to expand a shared body of knowledge, whereas QA was defined as an effort to ascertain whether a specific project met desired standards. However, the two categories increasingly overlap due to advances in bioinformatics and the shift toward open science. As few ethics review policies take these changes into account, it is often difficult to determine the appropriate level of review. Mislabeling can result in unnecessary burdens for the investigators or, conversely, in underestimation of the risks to participants. Therefore, it is important to develop a consistent method of selecting the review process for genomics and bioinformatics projects. This paper begins by discussing two case studies from the ICGC, followed by a literature review on the distinction between QA and research and a comparative analysis of ethics review policies from Canada, the United States, the United Kingdom, and Australia. These results are synthesized into a novel two-step decision tool for researchers and policymakers, which uses traditional criteria to sort clearly defined activities while requiring the use of actual risk levels to decide more complex cases.

Silos of genome data collection are being transformed into seamlessly connected, independent systems , Early data-sharing efforts have led to improved variant interpretation and development of treatments for rare diseases and some cancer types ( 1 – 3 ). However, such benefits will only be available to the general population if researchers and clinicians can access and make comparisons across data from millions of individuals.

Ad hoc approaches mix and match existing components , Historically, research ethics committees (RECs) have been guided by ethical principles regarding human experimentation intended to protect participants from physical harms and to provide assurance as to their interests and welfare. But research that analyzes large aggregate data sets, possibly including detailed clinical and genomic information of individuals, may require different assessment. At the same time, growth in international data-sharing collaborations adds stress to a system already under fire for subjecting multisite research to replicate ethics reviews, which can inhibit research without improving the quality of human subjects' protections ( 1 , 2 ). “Top-down” national regulatory approaches exist for ethics review across multiple sites in domestic research projects [e.g., United States ( 3 , 4 ), Canada ( 5 ), United Kingdom, ( 6 ), Australia ( 7 )], but their applicability for data-intensive international research has not been considered. Stakeholders around the world have thus been developing “bottom-up” solutions. We scrutinize five such ef orts involving multiple countries around the world, including resource-poor settings (table S1), to identify models that could inform a framework for mutual recognition of international ethics review (i.e., the acceptance by RECs of the outcome of each other's review).

Abstract There is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.

Clinical applications of next generation sequencing are growing at a tremendous pace. Currently the largest application of genetic testing in medicine occurs with newborn screening through state-mandated public health programs, and there are suggestions that sequencing could become a standard component of newborn care within the next decade. As such, newborn screening may appear to be a logical starting point to explore whole genome and whole exome sequencing on a population level. Yet, there are a number of ethical, social and legal implications about the use of a mandatory public health screening program that create challenges for the use of sequencing technologies in this context. Additionally, at this time we still have limited understanding and strategies for managing genomic data, supporting our conclusion that genome sequencing is not justified within population based public health programs for newborn screening.

Framing genome editing policy requires setting thresholds of acceptability , Balancing therapeutic prospects brought by scientific advances with regulation to address highly contested socioethical issues is the ultimate challenge in dealing with disruptive science. Human genome editing is a powerful tool that offers great scientific and therapeutic potential ( 1 , 2 ). Yet, it rejuvenates socioethical and policy questions surrounding the acceptability of germline modification.

The European Union (EU) approach to data protection consists of assessing the adequacy of the data protection offered by the laws of a particular jurisdiction against a set of principles that includes purpose limitation, transparency, quality, proportionality, security, access, and rectification. The EU's Data Protection Directive sets conditions on the transfer of data to third countries by prohibiting Member States from transferring to such countries as have been deemed inadequate in terms of the data protection regimes. In theory, each jurisdiction is evaluated similarly and must be found fully compliant with the EU's data protection principles to be considered adequate. In practice, the inconsistency with which these evaluations are made presents a hurdle to international data-sharing and makes difficult the integration of different data-sharing approaches; in the 20 years since the Directive was first adopted, the laws of only five countries from outside of the EU, Economic Area, or the European Free Trade Agreement have been deemed adequate to engage in data transfers without the need for further administrative safeguards.

Although Canada has not yet enacted any biobanking-specific privacy law, guidance and oversight are provided via various federal and provincial health and privacy-related laws as well as via ethics and policy documents. The primary policy document governing health research, the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans, provides the framework for the strong role of Research Ethics Boards in Canada, and limits research funding from Canada's three main federal funding agencies to those who agree to adhere to its policies. The broad consent model is gaining traction in Canada, although lack of legal and constitutional precedence for the broad consent or opt-out options makes this an evolving issue. In general, data is required to be coded; more specific security measures are outlined in guidelines that may be implemented by local policy. International sharing is allowed, and Canada meets the European Union's standards for receipt of data and samples.

A Special Report in Collaboration with the Research Center for Islamic Legislation and Ethics

Laws in the 20 jurisdictions studied for this project display many similar approaches to protecting privacy in biobank research. Although few have enacted biobank-specific legislation, many countries address biobanking within other laws. All provide for some oversight mechanisms for biobank research, even though the nature of that oversight varies between jurisdictions. Most have some sort of controlled access system in place for research with biobank specimens. While broad consent models facilitate biobanking, countries without national or federated biobanks have been slow to adopt broad consent. International guidelines have facilitated sharing and generally take a proportional risk approach, but many countries have provisions guiding international sharing and a few even limit international sharing. Although privacy laws may not prohibit international collaborations, the multi-prong approach to privacy unique to each jurisdiction can complicate international sharing. These symposium issues can serve as a resource for explaining the sometimes intricate privacy laws in each studied jurisdiction, outlining the key issues with regards to privacy and biobanking, and serving to describe a framework for the process of harmonization of privacy laws.

Autism spectrum disorder (ASD) is characterized by repetitive patterns of behaviour and impairments in social interactions and communication abilities. Although ASD is a heterogeneous disorder, it is a highly genetic condition for which genetic testing is routinely performed. Microarray analysis is currently the standard of care genetic test for ASD, however whole genome sequencing offers several key advantages and will likely replace microarrays as a frontline genetic test in the near future. The 2nd Consultation on Translation of Genomic Advances into Health Applications took place in the spring of 2014 to broadly explore the current and potential impacts of genomic advances in supporting personalized and family-centered care for autism and related developmental conditions. In anticipation of WGS becoming a standard of care test, we examine the policy landscape and highlight the lack of consistency among guidelines regarding what genomic information should be returned to patients and their families. We also discuss the need to create the infrastructure to share clinical WGS data with researchers in a systematic and ethically defensible manner.

Today, medical innovations arising from genetic research include the ability to predict, using genetic testing, the future health of certain individuals in particular as to their risk of developing certain diseases such as breast cancer. These advances have generated several therapeutic benefits but also entail new challenges for individuals. Indeed, genetic results generated may raise additional issues related to the use of this information outside of the therapeutic or medical research contexts. Many third parties such as insurers and employers have shown interest in using this information. In the insurance context, such use is likely to lead to a differential treatment of individuals based on their genetic characteristics at the time of purchase of personal insurance, potentially giving rise to the phenomenon of genetic discrimination. Unlike other jurisdictions, the law in Quebec does not provide specific rules on the use of genetic information. This status quo raises several issues in the context of insurance law. What is the scope of the duty to disclose of an insurance applicant and an insured concerning his genetic risks? What is the role of the insurer in the assessment of genetic risks? The study of various issues related to the possible use of genetic information in personal insurance and the duties of the applicant, the insured and the insurer upon subscription or renewal of an insurance policy reveals several uncertainties that may eventually require further clarifications from the legislator or the courts.

This paper proposes a set of recommendations for the return of research results and incidental findings in paediatrics. The Network of Applied Genetic Medicine of Quebec spearheaded the initiative to develop the Statement of Principles on the Return of Research Results and Incidental Findings, which was the result of a consultation process with clinical and research experts in the field. To formulate the Statement of Principles, the authors (i) reviewed empirical and grey literature on the return of research results and incidental findings in Europe and Canada, (ii) conducted a qualitative study of stakeholder groups, (iii) developed, and (iv) validated the recommendations through consultations with the stakeholder groups. The Statement of Principles provides a useful disclosure tool for deciding when, and under what circumstances to return research results and incidental findings. It addresses the issue of return of results in genetic research generally, and has also specific principles for various research contexts, including paediatric research. It delineates ethical issues unique to paediatric research, and provides a framework to guide research ethics committees as well as the research community in addressing these issues.

With the progress in bioinformatics, genomics, and epidemiology, biobanks, as repositories of populations’ biological samples as well as of personal and medical information, are becoming an essential research tool. Despite the potential benefits biobanks may bring and the options presented by some of the current biobanks’ consent policies, there remain ethical concerns regarding the autonomy and dignity of research participants if consent is not fully informed as dictated in the terms of traditional informed consent. This article aims at providing an overview of the approaches taken by the main international norms with respect to informed and broad consent and how well these norms are integrated by biobanks or biobank consortia. We conclude that broad consent could be an important tool to achieve the benefits of large-scale biobanks projects. If it is to be accepted, its regulation and implementation need to be mindful of the participant’s dignity and autonomy and sensitive to the need for international coherence and harmonization.

The advent and refinement of sequencing technologies has resulted in a decrease in both the cost and time needed to generate data on the entire sequence of the human genome. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform address herein the important issues and challenges surrounding the potential use of sequencing technologies in publicly funded newborn screening (NBS) programmes. This statement presents the relevant issues and culminates in a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers regarding the necessary considerations for the use of genome sequencing technologies and approaches in NBS programmes. The primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood.

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

Data and sample sharing constitute a scientific and ethical imperative but need to be conducted in a responsible manner in order to protect individual interests as well as maintain public trust. In 2014, the Global Alliance for Genomics and Health (GA4GH) adopted a common Framework for Responsible Sharing of Genomic and Health-Related Data. The GA4GH Framework is applicable to data sharing in the stem cell field, however, interpretation is required so as to provide guidance for this specific context. In this paper, the International Stem Cell Forum Ethics Working Party discusses those principles that are specific to translational stem cell science, including engagement, data quality and safety, privacy, security and confidentiality, risk–benefit analysis and sustainability.

The biggest challenge in twenty-first century data-intensive genomic science, is developing vast computer infrastructure and advanced software tools to perform comprehensive analyses of genomic data sets for biomedical research and clinical practice. Researchers are increasingly turning to cloud computing both as a solution to integrate data from genomics, systems biology and biomedical data mining and as an approach to analyze data to solve biomedical problems. Although cloud computing provides several benefits such as lower costs and greater efficiency, it also raises legal and ethical issues. In this article, we discuss three key ‘points to consider’ (data control; data security, confidentiality and transfer; and accountability) based on a preliminary review of several publicly available cloud service providers’ Terms of Service. These ‘points to consider’ should be borne in mind by genomic research organizations when negotiating legal arrangements to store genomic data on a large commercial cloud service provider’s servers. Diligent genomic cloud computing means leveraging security standards and evaluation processes as a means to protect data and entails many of the same good practices that researchers should always consider in securing their local infrastructure.

Whole-exome sequencing (WES) carries the potential to facilitate the identification of disease causing genes. This is particularly relevant concerning rare diseases, which proves particularly difficult for physicians to diagnose. However, the complexity of this technology renders its applicability onto the clinical setting uncertain. Our study thus aims to understand physicians’ perspectives regarding the clinical utility of WES, particularly for providing a diagnosis for patients with rare diseases. Ten semi-structured interviews were conducted with physicians with experience and familiarity with WES, and the major themes that emerged from our interviews were (i) the relevance of WES in diagnosing patients with rare diseases (appropriateness); (ii) the cost-effectiveness of WES (accessibility), (iii) the practical issues related to the clinical implementation of WES (practicability); and (iv) ethical, legal and social issues (acceptability). Our study highlights how the clinical implementation of WES presents additional challenges where rare diseases are taken into consideration.

There are few better examples of the need for data sharing than in the rare disease community, where patients, physicians, and researchers must search for “the needle in a haystack” to uncover rare, novel causes of disease within the genome. Impeding the pace of discovery has been the existence of many small siloed datasets within individual research or clinical laboratory databases and/or disease-specific organizations, hoping for serendipitous occasions when two distant investigators happen to learn they have a rare phenotype in common and can “match” these cases to build evidence for causality.

Global collaboration in genomic research is increasingly both a scientific reality and an ethical imperative. This past decade has witnessed the emergence of six new, interconnected areas of ethical consensus and emphasis for policy in genomics: governance, security, empowerment, transparency, the right not to know, and globalization.

The authors provide a comprehensive survey of international legislation and policies guiding the return of whole-genome-sequencing-based genetic testing results to patients or study participants, within the context of both clinical and research settings.

Large-scale epigenome mapping by the NIH Roadmap Epigenomics Project, the ENCODE Consortium and the International Human Epigenome Consortium (IHEC) produces genome-wide DNA methylation data at one base-pair resolution. We examine how such data can be made open-access while balancing appropriate interpretation and genomic privacy. We propose guidelines for data release that both reduce ambiguity in the interpretation of open-access data and limit immediate access to genetic variation data that are made available through controlled access.

Major funding agencies should ensure that large biological data sets are stored in cloud services to enable easy access and fast analysis, say Lincoln D. Stein and colleagues.

There is a growing international agreement on the need to provide greater access to research data and bio-specimen collections to optimize their long-term value and exploit their potential for health discovery and validation. This is especially evident for rare disease research. Currently, the rising value of data and bio-specimen collections does not correspond with an equal increase in data/sample-sharing and data/sample access. Contradictory legal and ethical frameworks across national borders are obstacles to effective sharing: more specifically, the absence of an integrated model proves to be a major logistical obstruction. The Charter intends to amend the obstacle by providing both the ethical foundations on which data sharing should be based, as well as a general Material and Data Transfer Agreement (MTA/DTA). This Charter is the result of a careful negotiation of different stakeholders' interest and is built on earlier consensus documents and position statements, which provided the general international legal framework. Further to this, the Charter provides tools that may help accelerate sharing. The Charter has been formulated to serve as an enabling tool for effective and transparent data and bio-specimen sharing and the general MTA/DTA constitutes a mechanism to ensure uniformity of access across projects and countries, and may be regarded as a consistent basic agreement for addressing data and material sharing globally. The Charter is forward looking in terms of emerging issues from the perspective of a multi-stakeholder group, and where possible, provides strategies that may address these issues.

Nature Biotechnology asks selected members of the international community to comment on the ethical issues raised by the prospect of CRISPR-Cas9 engineering of the human germline.

In this letter to the editor, we respond to the recent publication by Philibert et al. Methylation array data can simultaneously identify individuals and convey protected health information: an unrecognized ethical concern (Clinical Epigenetics 2014, 6:28). Further discussion of the issues raised by the risk of re-identification of epigenetic methylation data is needed, and a more nuanced approach should be taken with respect to its implications for data sharing policy than the one provided.

Summary Human somatic cell reprogramming is a leading technology for accelerating disease modeling and drug discovery. The Deriving Induced Stem Cells Using Stored Specimens (DISCUSS) project is a consensus-building initiative designed to consider how human somatic cells obtained under general biomedical research protocols can be used in induced pluripotent stem cell (iPSC) derivation. We previously published a draft list of points to consider for the use of previously collected specimens in iPSC research and then initiated a structured feedback and comment process. Here, we present a summary of this feedback and revised list of points to consider.

To understand the causes of disease and improve diagnosis and treatment regimes, biomedical researchers need access to large numbers of well-characterized data and samples. Over the past decade, biobanks have been established across Europe to collect and manage access to data and samples. The challenge that we face is how to develop the tools and collaborations to enable researchers to access samples and data from a network of biobanks, rather than applying to individual biobanks. One of the perceived stumbling blocks to achieving this is represented by the different legal requirements in each country. The aim of the BioSHaRE-European Union (EU) project is to address these challenges by developing tools and methods for researchers to access and use pooled data from different cohort and biobank studies. The purpose of this article is to identify and compare the key legal requirements regarding research use of data across biobanks based in Finland, Germany, the Netherlands, Norway and the UK. Our investigation starts with the analysis of the key differences for the use of data between these countries. As a result, we identified three key areas where legal requirements differ across the five BioSHaRE-EU jurisdictions, namely, in the definition of personal data, the requirements regarding pseudonymization and processing for medical research purposes. This article provides an overview of these differences and describes them in the light of the proposed EU regulation on data protection.

"Includes state-of-the-art principles, tools such as biomarkers and early clinical trials, algorithms of translational science in medicine Provides in-depth description of special translational aspects in the currently most successful areas of clinical translation, namely oncology and immunology Covers status of institutionalization of translational medicine, networking structures and outcomes at the level of marketing authorization"--

In an era of unrivalled sequencing, computation and networking capability, international sharing of genomic samples and data is becoming a modus operandi for modern medical research. Researchers are collaborating to establish large collections with global scale. Having never before set foot outside the cell, the molecules that shape us are being digitized and launched across the globe. Protecting individual privacy interests in this information is a central challenge of the genomic research era. This article reviews international privacy norms governing human genomic biobanks and databases. It will not directly consider biobanks established for other health-related purposes, such as screening or therapy. A genomic biobank is “a hybrid infrastructure,” an organized collection of human biological material combined with associated health information: physical measurements, outcome data in medical records, and epidemiological information, as well as genomic data derived from the samples.

Objectives: There have been multiple calls for explicit integration of ethical, legal, and social issues (ELSI) in health technology assessment (HTA) and addressing ELSI has been highlighted as key in optimizing benefits in the Omics/Personalized Medicine field. This study examines HTAs of an early clinical example of Personalized Medicine (gene expression profile tests [GEP] for breast cancer prognosis) aiming to: (i) identify ELSI; (ii) assess whether ELSIs are implicitly or explicitly addressed; and (iii) report methodology used for ELSI integration. Methods: A systematic search for HTAs (January 2004 to September 2012), followed by descriptive and qualitative content analysis. Results: Seventeen HTAs for GEP were retrieved. Only three (18%) explicitly presented ELSI, and only one reported methodology. However, all of the HTAs included implicit ELSI. Eight themes of implicit and explicit ELSI were identified. “Classical” ELSI including privacy, informed consent, and concerns about limited patient/clinician genetic literacy were always presented explicitly. Some ELSI, including the need to understand how individual patients’ risk tolerances affect clinical decision-making after reception of GEP results, were presented both explicitly and implicitly in HTAs. Others, such as concern about evidentiary deficiencies for clinical utility of GEP tests, occurred only implicitly. Conclusions: Despite a wide variety of important ELSI raised, these were rarely explicitly addressed in HTAs. Explicit treatment would increase their accessibility to decision-makers, and may augment HTA efficiency maximizing their utility. This is particularly important where complex Personalized Medicine applications are rapidly expanding choices for patients, clinicians and healthcare systems.

Adopting a multi-disciplinary and comparative approach, this book focuses on emerging and innovative attempts to tackle privacy and legal issues in cloud computing, such as personal data privacy, security and intellectual property protection. Leading international academics and practitioners in the fields of law and computer science examine the specific legal implications of cloud computing pertaining to jurisdiction, biomedical practice and information ownership. This collection offers original and critical responses to the rising challenges posed by cloud computing.

Edward S Dove, Ma’n H Zawati, 2014-2015 8-1 McGill Journal of Law and Health 79, 2015 CanLIIDocs 141

With a population of over 1.3 billion, China is the most populous country in the world. It is facing an acute aging population problem, with a projected 440 million residents over age 60 and 101 million over age 80 by 2050. Furthermore, rapid industrialization and urbanization in China have resulted in serious air pollution and associated public health problems, including an increase in respiratory diseases and cancers. These and other demographic trends have generated concerns about the cost of health care and its impact on population health. In recent years, the Chinese government has invested heavily in the fields of translational research and biobanking with the hope that research in both fields can yield effective solutions to improve the public’s health and quality of life. The establishment of national biobanks was identified as a major initiative needed for the biomedical industry in the 12th Five-Year National Development Plan of Strategic Emerging Industries promulgated by the State Council in 2012.

Rare diseases (RD) refer to a collection of approximately 5,000–8,000 individual diseases that have a low prevalence and are often genetic in origin. While RD can manifest throughout life, they frequently affect children and newborns. Common characteristics include being severe, disabling, life-threatening, degenerative and affecting different organ systems. The burden of RD is often exacerbated by a lack of specific treatments. Whilst there is etiological heterogeneity, there is overlap in cellular and molecular pathways. Amongst specialists, there is legitimate hope that based on genetic knowledge and pathway definition, a new medical classification system, currently called “precision medicine”, will be developed, which may change our view on how to apply shared therapeutic targets. Thus, collection of clinical and genetic data and biospecimens (in biobanks) will play an increasing role in diagnoses and development of therapies for RD. Biobanks are maintained collaboratively by researchers or their institutions, and involve a delicate balance between health policy objectives, academic research, public good outcomes, and community trust. Due to the nature of RD, international cooperation is critical for sharing limited numbers of RD samples and achieving a critical mass. Here we review the current and future direction of RD biobanks and discuss research and development stemming from the use of biospecimens to improve management of RD.

Paediatric genomic research raises particularly challenging questions on whether and under what circumstances to return research results. In the paediatric context, decision-making is guided by the best interests of the child framework, as enshrined in the 1989 international Convention on the Rights of the Child. According to this Convention, rights and responsibilities are shared between children, parents, researchers, and the state. These "relational" obligations are further complicated in the context of genetic research.

ABSTRACT Purpose To explore parental perceptions and experiences regarding the return of genomic incidental research findings in children with rare diseases. Methods Parents of children affected by various rare diseases were invited to participate in focus groups or individual telephone interviews in Montreal and Ottawa. Fifteen participants were interviewed and transcriptions were analysed using thematic analysis. Results Four emergent themes underscored parental enthusiasm for receiving incidental findings concerning their child’s health: (1) right to information; (2) perceived benefits and risks; (3) communication practicalities: who, when, and how; and (4) service needs to promote the communication of incidental findings. Parents believed they should be made aware of all results pertaining to their child’s health status, and that they are responsible for transmitting this information to their child, irrespective of disease severity. Despite potential negative consequences, respondents generally perceived a favourable risk-benefit ratio in receiving all incidental findings. Conclusions Understanding how parents assess the risks and benefits of returning incidental findings is essential to genomic research applications in paediatric medicine. The authors believe the study findings will contribute to establishing future best practices, although further research is needed to evaluate the impact of parental decisions on themselves and their child.

Data sharing models designed to facilitate global business provide insights for improving transborder genomic data sharing. We argue that a flexible, externally endorsed, multilateral arrangement, combined with an objective third-party assurance mechanism, can effectively balance privacy with the need to share genomic data globally.

Fostering data sharing is a scientific and ethical imperative. Health gains can be achieved more comprehensively and quickly by combining large, information-rich datasets from across conventionally siloed disciplines and geographic areas. While collaboration for data sharing is increasingly embraced by policymakers and the international biomedical community, we lack a common ethical and legal framework to connect regulators, funders, consortia, and research projects so as to facilitate genomic and clinical data linkage, global science collaboration, and responsible research conduct. Governance tools can be used to responsibly steer the sharing of data for proper stewardship of research discovery, genomics research resources, and their clinical applications. In this article, we propose that an international code of conduct be designed to enable global genomic and clinical data sharing for biomedical research. To give this proposed code universal application and accountability, however, we propose to position it within a human rights framework. This proposition is not without precedent: international treaties have long recognized that everyone has a right to the benefits of scientific progress and its applications, and a right to the protection of the moral and material interests resulting from scientific productions. It is time to apply these twin rights to internationally collaborative genomic and clinical data sharing.

Inherited monogenic disease has an enormous impact on the well-being of children and their families. Over half of the children living with one of these conditions are without a molecular diagnosis because of the rarity of the disease, the marked clinical heterogeneity, and the reality that there are thousands of rare diseases for which causative mutations have yet to be identified. It is in this context that in 2010 a Canadian consortium was formed to rapidly identify mutations causing a wide spectrum of pediatric-onset rare diseases by using whole-exome sequencing. The FORGE (Finding of Rare Disease Genes) Canada Consortium brought together clinicians and scientists from 21 genetics centers and three science and technology innovation centers from across Canada. From nation-wide requests for proposals, 264 disorders were selected for study from the 371 submitted; disease-causing variants (including in 67 genes not previously associated with human disease; 41 of these have been genetically or functionally validated, and 26 are currently under study) were identified for 146 disorders over a 2-year period. Here, we present our experience with four strategies employed for gene discovery and discuss FORGE’s impact in a number of realms, from clinical diagnostics to the broadening of the phenotypic spectrum of many diseases to the biological insight gained into both disease states and normal human development. Lastly, on the basis of this experience, we discuss the way forward for rare-disease genetic discovery both in Canada and internationally.

With the development and increasing accessibility of new genomic tools such as next-generation sequencing, genome-wide association studies, and genomic stratification models, the debate on genetic discrimination in the context of life insurance became even more complex, requiring a review of current practices and the exploration of new scenarios. In this perspective, a multidisciplinary group of international experts representing different interests revisited the genetics and life insurance debate during a 2-day symposium ‘Life insurance: breast cancer research and genetic risk prediction seminar’ held in Quebec City, Canada on 24 and 25 September 2012. Having reviewed the current legal, social, and ethical issues on the use of genomic information in the context of life insurance, the Expert Group identified four main questions: (1) Have recent developments in genomics and related sciences changed the contours of the genetics and life insurance debate? (2) Are genomic results obtained in a research context relevant for life insurance underwriting? (3) Should predictive risk assessment and risk stratification models based on genomic data also be used for life insurance underwriting? (4) What positive actions could stakeholders in the debate take to alleviate concerns over the use of genomic information by life insurance underwriters? This paper presents a summary of the discussions and the specific action items recommended by the Expert Group.

Genomic researchers increasingly are faced with difficult decisions about whether, under what circumstances, and how to return research results and significant incidental findings to study participants. Many have argued that there is an ethical-maybe even a legal-obligation to disclose significant findings under some circumstances. At the international level, over the last decade there has begun to emerge a clear legal obligation to return significant findings discovered during the course of research. However, there is no explicit legal duty to disclose in the United States. This creates legal uncertainty that may lead to unmanaged variation in practice and poor quality care. This article discusses liability risks associated with the disclosure of significant research findings for investigators in the United States.

Purpose This article proposes recommendations for the use of whole-genome and whole-exome (WGS/WES) sequencing in clinical practice, endorsed by the board of directors of the Canadian College of Medical Geneticists. The publication of statements and recommendations by several international and national organisations on clinical WGS/WES has prompted a need for Canadianspecific guidance. Methods A multi-disciplinary group consisting of lawyers, ethicists, genetic researchers, and clinical geneticists was assembled to review existing guidelines on WGS/WES and identify provisions relevant to the Canadian context. Results Definitions were provided to orient the recommendations and to minimize confusion with other recommendations. Recommendations include the following: WGS/WES should be used in a judicious and cost-efficient manner; WGS/WES should be used to answer a clinical question; and physicians need to explain to adult patients the nature of the results that could arise, so as to allow them to make informed choices over whether to take the test and which results they wish to receive. Recommendations are also provided for WGS/WES in the pediatric context, and for when results implicate patients’ family members. Conclusion These recommendations are only a proposal to be developed into comprehensive Canadianbased guidelines. They aim to promote discussion about the reporting of WGS/WES results, and to encourage the ethical implementation of these new technologies in the clinical setting.

While the realm of bioethics has traditionally focused on the rights of the individual and held autonomy as a defining principle, public health ethics has at its core a commitment to the promotion of the common good. While these two domains may at times conflict, concepts arising in one may also be informative for concepts arising in the other. One example of this is the concept of a “right not to know.” Recent debate suggests that just as there is a “right to know” information about one's genetic status, there is a parallel “right not to know” when it comes to genetic information that if communicated, could be detrimental to an individual's social or psychological well-being. As new genetic technologies continue to change the nature of genetic testing and screening, it is crucial that normative frameworks to guide and assess genetic public health initiatives be developed. In this context, the question of whether a “right not to know” may also be said to exist for populations on a public health level merits attention.

Large-scale sequencing tests, including whole-exome and whole-genome sequencing (WES/WGS), are rapidly moving into clinical use. Sequencing is already being used clinically to identify therapeutic opportunities for cancer patients who have run out of conventional treatment options, to help diagnose children with puzzling neurodevelopmental conditions, and to clarify appropriate drug choices and dosing in individuals. To evaluate and support clinical applications of these technologies, the National Human Genome Research Institute (NHGRI) and National Cancer Institute (NCI) have funded studies on clinical and research sequencing under the Clinical Sequencing Exploratory Research (CSER) program as well as studies on return of results (RoR). Most of these studies use sequencing in real-world clinical settings and collect data on both the application of sequencing and the impact of receiving genomic findings on study participants. They are occurring in the context of controversy over how to obtain consent for exome and genome sequencing.

Genomics research is becoming increasingly globally connected and collaborative, contesting traditional ethical and legal boundaries between global and local research practice. As well, global data-driven genomics research holds great promise for health discoveries. Yet, paradoxically, current research ethics review systems around the world challenge potential improvements in human health from such research and thus undermine respect for research participants. Case reports illustrate that the current system is costly, fragmented, inefficient, inadequate, and inconsistent. There is an urgent need to improve the governance system of ethics review to enable secure and seamless genomic and clinical data sharing across jurisdictions.

With the costs of genomic and genetic testing rapidly decreasing, private companies have begun to offer consumers, including minors, the opportunity to receive a genetic analysis of their DNA. The availability of direct-to-consumer genetic testing (DTC-GT) will inevitably result in patients approaching their healthcare providers for interpretation of results, referrals for follow-up tests or provision of personalized medicine. As most healthcare systems require a referral for access to a specialist, the patients are likely to approach primary care providers. The issue of what the professional obligations are for the primary care physician in the case where they did not order the test is not new. The growing DTC-GT movement will add a ‘new twist to an old problem.‘ Best practice recommendations regarding the value of DTC-GT, as well as the identification of current ethical, legal and social implications are urgently needed.

Summary Human somatic cell reprogramming is a leading technology for accelerating disease modeling and drug discovery. Research organizations are sponsoring initiatives to create libraries of induced pluripotent stem cell (iPSC) lines for broad distribution and application. Donor informed consent plays a critical role in supporting the ethical conduct of iPSC research. To date, our organizations have focused on informed consent considerations for somatic cell collection intended specifically for iPSC derivation and distribution. This article considers how somatic cells obtained under general (biomedical) research protocols can be used for iPSC derivation. We present draft Points to Consider regarding the use of human somatic cells for iPSC research. Our goal is to initiate a process designed to develop consensus for the use of previously collected specimens for iPSC research. We anticipate publishing final considerations in early 2014.

While the importance of intrafamilial communication of hereditary cancer risk has been acknowledged, the factors that promote and act as barriers to patients disclosing their information to their families are complex and emerging. This raises the question: How are patients guided in practice to contemplate intrafamilial communication? Focusing on breast cancer, we conducted an exploratory study examining current resources supporting patients and health-care professionals, and isolated the messages surrounding intrafamilial communication of cancer risk. We find the duty for health-care professionals to counsel patients regarding intrafamilial communication is acknowledged to varying degrees by multiple actors in the cancer care delivery landscape, including health-care professional associations, health service organizations, and patient groups. A range of medical, psychosocial, and other factors underlying intrafamilial communication are acknowledged in messages to patients. Patients, however, are often referred to a single group of health-care professionals to discuss their diverse and complex needs. At the same time, messages aimed at patients appear to place the emphasis on barriers that could exist for patients contemplating intrafamilial communication, while highlighting the benefits families derive from such communication. Taken together, this points to a lack of coherence within materials directed to patients and suggests the need to do coordinated research among stakeholders to address two related issues: (1) determining who are the actors best positioned to send messages surrounding intrafamilial communication to patients and (2) addressing the content of messages conveyed in patient materials.

The purpose of this study was to explore the attitudes of genomics researchers in a pediatric setting in the context of regulatory guidance recommending the disclosure of clinically significant research findings.

Rare disease research is threatened by proposed changes to European privacy laws.

Genotype-Driven Recruitment (GDR) is a research design that recruits research participants based on genotype rather than based on the presence or absence of a particular condition or clinical outcome. Analyses of the ethical issues of GDR studies, and the recommendations derived from these analyses, are based on GDR research designs that make use of genetic information already collected in previous studies. However, as genotyping becomes more affordable, it is expected that genotypic information will become a common part of the information stored in biobanks and held in health care records. Furthermore, individuals will increasingly gain knowledge of their own genotypes through Direct-to-Consumer services. One can therefore foresee that individuals will be invited to participate not only in follow-up GDR studies but also in original GDR studies because genetic information about them is available. These individuals may or may have not participated in research before and may or may not be aware that their genetic information is available for research.

There has been much investment in research on the ethical, legal and social issues (ELSI) associated with genetic and genomic research. This research should inform the development of the relevant policy. So far, much of the relevant policy - such as in the areas of patents, genetic testing and genetic discrimination - seems to be informed more by speculation of harm and anecdote than by available evidence. Although a quest for evidence cannot always be allowed to delay policy choice, it seems axiomatic to us that policy options are improved by the incorporation of evidence.

Since the late 1980s, genetic discrimination has remained one of the major concerns associated with genetic research and clinical genetics. Europe has adopted a plethora of laws and policies, both at the regional and national levels, to prevent insurers from having access to genetic information for underwriting. Legislators from the United States and the United Kingdom have also felt compelled to adopt protective measures specifically addressing genetics and insurance. But does the available evidence really confirm the popular apprehension about genetic discrimination and the subsequent genetic exceptionalism?

Clinical trial samples collected for pharmacogenomic and future research are vital resources for the development of safe and effective drugs, yet collecting adequate, representative sample sets in global trials is challenging. The Drug Information Association (DIA) sponsored a workshop on future use sampling in September 2011, bringing together experts from regulatory agencies, academia and industry to discuss challenges to future use sample collection and identify actions to improve collection. Several common themes and associated action items emerged, including the need for international guidance on the collection of samples for future research; additional discussion related to coding, scope of research, and return of research results; and additional education about pharmacogenomic/future research and the importance of long-term storage of specimens.

Decision-making dynamics in pediatric research have their foundation in the principle of the ‘best interests of the child’. The introduction of new sequencing technologies and the concomitant debate surrounding the return of research results and incidental findings are, however, challenging the interpretation of this principle. A comparative analysis of international and national approaches to the issue (USA, Canada, France, Spain and the UK) reveals not only the emergence of context-specific pediatric policy in this regard, but one that is ‘personalized’ to the child – that is, what is clinically significant and actionable during childhood.

Clarissa Allen, Yann Joly, Palmira Granados Moreno, 2013 7-1 McGill Journal of Law and Health 85, 2013 CanLIIDocs 35

Pharmacogenomics has been described as one of the most promis-ing research areas to stem from the genetic revolution [24].Proponents proclaim it has the potential to transform health careand pharmaceutical development, leading the way toward a new eraof personalizedmedicine whereby the right amount of the right kindof drug would be provided to the right patient. Pharmacogenomicstratification is becoming more frequent in clinical drug trials, andalready a handful of pharmacogenomic tests have been approvedby regulators and are now included as part of drug labels in manydeveloped countries.

Non-therapeutic trials in which terminally ill cancer patients are asked to undergo procedures such as biopsies or venipunctures for research purposes, have become increasingly important to learn more about how cancer cells work and to realize the full potential of clinical research. Considering that implementing non-therapeutic studies is not likely to result in direct benefits for the patient, some authors are concerned that involving patients in such research may be exploitive of vulnerable patients and should not occur at all, or should be greatly restricted, while some proponents doubt whether such restrictions are appropriate. Our objective was to explore clinician-researcher attitudes and concerns when recruiting patients who are in advanced stages of cancer into non-therapeutic research.

There is a noticeable lack of international regulation on personal data exchange and management in research. This article sheds light in this area by describing how the International Cancer Genome Consortium is developing policies and procedures to address the ethical and legal issues raised by the international transfer of data and results. These policies and procedures aim, first and most importantly, to safeguard the interests of the research participants and other involved stakeholders and, secondly, to facilitate the sharing of data and results to realize greater benefits from this kind of internationally collaborative genetic research.

Translation of pharmacogenomics to public health action is at the epicenter of the life sciences agenda. Post-genomics knowledge is simultaneously co-produced at multiple scales and locales by scientists, crowd-sourcing and biological citizens. The latter are entrepreneurial citizens who are autonomous, self-governing and increasingly conceptualizing themselves in biological terms, ostensibly taking responsibility for their own health, and engaging in patient advocacy and health activism. By studying these heterogeneous 'scientific cultures', we can locate innovative parameters of collective action to move pharmacogenomics to practice (personalized therapeutics). To this end, we reconceptualize knowledge-based innovation as a complex ecosystem comprising 'actors' and 'narrators'. For robust knowledge translation, we require a nested post-genomics technology governance system composed of first-order narrators (for example, social scientists, philosophers, bioethicists) situated at arm's length from innovation actors (for example, pharmacogenomics scientists). Yet, second-order narrators (for example, an independent and possibly crowd-funded think-tank of citizen scholars, marginalized groups and knowledge end-users) are crucial to prevent first-order narrators from gaining excessive power that can be misused in the course of steering innovations. To operate such 'self-calibrating' and nested innovation ecosystems, we introduce the concept of 'wiki-governance' to enable mutual and iterative learning among innovation actors and first- and second-order narrators.

By characterizing the geographic and functional spectrum of human genetic variation, the 1000 Genomes Project aims to build a resource to help to understand the genetic contribution to disease. Here we describe the genomes of 1,092 individuals from 14 populations, constructed using a combination of low-coverage whole-genome and exome sequencing. By developing methods to integrate information across several algorithms and diverse data sources, we provide a validated haplotype map of 38 million single nucleotide polymorphisms, 1.4 million short insertions and deletions, and more than 14,000 larger deletions. We show that individuals from different populations carry different profiles of rare and common variants, and that low-frequency variants show substantial geographic differentiation, which is further increased by the action of purifying selection. We show that evolutionary conservation and coding consequence are key determinants of the strength of purifying selection, that rare-variant load varies substantially across biological pathways, and that each individual contains hundreds of rare non-coding variants at conserved sites, such as motif-disrupting changes in transcription-factor-binding sites. This resource, which captures up to 98% of accessible single nucleotide polymorphisms at a frequency of 1% in related populations, enables analysis of common and low-frequency variants in individuals from diverse, including admixed, populations.

It can be asserted that the stem cell field be classified as a global enterprise [1] , as evidenced by the proliferation of transnational stem cell initiatives, alliances, networks and institutions. Moreover, the sustainability of the field is – to a great extent – dependent on the ability of such actors to enable cross-jurisdictional collaboration by fostering the sharing of stem cell-related resources and data [1] . Kofi Annan’s statement that “arguing against globalization is like arguing against the law of gravity” [101] could not be more true when applied to the context of stem cells.

There are an increasing number of population studies collecting data and samples to illuminate gene-environment contributions to disease risk and health. The rising affordability of innovative technologies capable of generating large amounts of data helps achieve statistical power and has paved the way for new international research collaborations. Most data and sample collections can be grouped into longitudinal, disease-specific, or residual tissue biobanks, with accompanying ethical, legal, and social issues (ELSI). Issues pertaining to consent, confidentiality, and oversight cannot be examined using a one-size-fits-all approach—the particularities of each biobank must be taken into account. It remains to be seen whether current governance approaches will be adequate to handle the impact of next-generation sequencing technologies on communication with participants in population biobanking studies.

While modern genomics research often adheres to community norms emphasizing open data sharing, many genomics institutes and projects have recently nuanced such norms with a corpus of data release policies. In particular, publication moratoria and data retention policies have been enacted to ‘reward’ data producers and ensure data quality control. Given the novelty of these policies, this article seeks to identify and analyse the main features of data retention and publication moratoria policies of major genomics institutes and projects around the world. We find that as more collaborative genomics projects are created, and further genomic research discoveries are announced, the need for more sophisticated yet practical and effective policies will increase. Reward systems should be implemented that recognize contributions from data producers and acknowledge the need to remain dedicated to the goals of open data sharing. To this end, in addition to the current choices of employing data retention or publication moratoria policies, alternative models that would be easier to implement or less demanding on open science should also be considered.

Biobanks are adopting various modes of public engagement to close the agency gap between participants and biobank builders. We propose a wiki-governance model for biobanks that harnesses Web 2.0, and which gives citizens the ability to collaborate in biobank governance and policymaking.

We need an international infrastructure for the ethical, legal, and social implications of genomic research. , Anticipating and addressing the ethical, legal, and social implications (ELSI) of scientific developments has been a key feature of the genomic research agenda ( 1 – 4 ). Research in genomics is advancing by developing common infrastructures and research platforms, open-access and sharing policies, and new forms of international collaborations ( 5 – 12 ). In this paper, we outline a proposal to establish a “collaboratory” ( 13 ) for ELSI research to enable it to become more coordinated, responsive to societal needs, and better able to apply the research knowledge it generates at the global level. Current ELSI research is generally nationally focused, with investigator-initiated approaches that are not always aligned with the developments in international genomics research. This makes it difficult to efficiently leverage findings that impact global practice and policy. Moreover, as translational genomic research design challenges become more pressing ( 14 ), ELSI research will need to develop greater capacity to respond rapidly to new developments. The ELSI 2.0 Initiative is designed to catalyze international collaboration in ELSI genomics and to enable those in the field to better assess the impact and dynamics of global genome research.

The 1000 Genomes Project was launched as one of the largest distributed data collection and analysis projects ever undertaken in biology. In addition to the primary scientific goals of creating both a deep catalog of human genetic variation and extensive methods to accurately discover and characterize variation using new sequencing technologies, the project makes all of its data publicly available. Members of the project data coordination center have developed and deployed several tools to enable widespread data access.

Prompted by an increased interest of both research participants and the patient advocacy community in obtaining information about research outcomes and on the use of their biological samples; the international community has begun to debate the emergence of an ethical ‘duty’ to return research results to participants. Furthermore, the use of new technologies (e.g., whole-genome and -exome sequencing) has revealed both genetic data and incidental findings with possible clinical significance. These technologies together with the proliferation of biorepositories, provide a compelling rationale for governments and scientific institutions to adopt prospective policies. Given the scarcity of policies in the context of stem cell research, a discussion on the scientific, ethical and legal implications of disclosing research results for research participants is needed. We present the International Stem Forum Ethics Working Party’s Policy Statement and trust that it will stimulate debate and meet the concerns of researchers and research participants alike.

Bioscience has recently undergone a series of knowledge-based and technological revolutions. A critical consequence has been increasing recognition of the need to invest in infrastructure. Good access to data (and samples) from multiple studies is axiomatic to the value of this infrastructure. Access must be streamlined, secure, and based upon transparent and ‘fair’ decision making. It must be clear who has created and who has used which data. Ethico-legal policies and guidelines, which reflect dominant local cultural and societal norms, must take account of the increasingly global nature of bioscience research. A robust data infrastructure must also be attentive to the translational aims and social impact of its knowledge generation. In order to maintain the trust of its constituency – the general public as well as professional, political, commercial stakeholders – it must develop mechanisms to take account of all of these perspectives. These considerations form the basis of an emerging data economy. Building on extant achievements and pursuing the ideas outlined here could revolutionise the way we use and manage large-scale data. They have critical implications for biomedical and public health research communities and will be of central relevance for healthcare managers and policy makers, governments and industry. However, if the major challenges are to be met we must continue to invest,both nationally and internationally, in developing the cooperative infrastructures that provide a complementary foil to competitive resourcing mechanisms that drive hypothesis-driven science.

National biobank infrastructures are now being implemented in several European countries. Individually, biobanks are invaluable as national research resources; collectively, they are the critical elements needed for the actualization of the pan-European biobank infrastructure. The national biobank infrastructures are confronted with a number of challenges of legal, ethical, political, societal, financial and educational nature which must be articulated and addressed in order to optimize the use of the biobanks in national and international research. The community of researchers involved with these biobanks has charted the most pressing issues experienced by the national biobanks in their nascent stages of development. Our findings reveal great commonalities in the nature of the challenges that the national hubs are facing. These challen ges and the strategies developed to address them are described in this paper

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Managers of genomic biobanks constantly face ethical and legal challenges ranging from issues associated with the informed consent process to procedural concerns related to access by researchers. Yet, with the availability of next-generation sequencing technologies, one topic is emerging as the focus of ongoing debate: the return of individual research results and incidental findings to participants. This article examines this topic from an international perspective, where policies and guidelines discussing the matter in the context of genomic biobanks and genomic research are analyzed and commented. This approach aims to highlight the shortcomings of these international norms, mainly the danger arising from both the therapeutic misconception and the conflation of research results with incidental findings. This article suggests some elements to consider in order to complement available guidance at the international level.

Efforts to improve research outcomes have resulted in genomic researchers being confronted with complex and seemingly contradictory instructions about how to perform their tasks. For example, increasing pressure to commercialise (academic) research is paralleled by pressure to collaborate, share data, and disseminate knowledge quickly so as to encourage scientific progress, maximise research impact, and meet humanitarian goals. This article briefly explores some of the relevant instructions in Canada and the United Kingdom and concludes that commercialisation and more open collaborative practices are not necessarily irreconcilable. They should be viewed as complementary elements of an innovation framework for which more evidence must be gathered with respect to the impact of this coexistence.

Biobanks are promising instruments of biomedical research and of transnational medicine in particular. Ethical, legal and social issues associated with biobanking, however, have recently led to a more critical view on this concept. All efforts addressing these concerns have been grounded on well-established standards of biomedical ethics such as informed consent procedures, protection of individual autonomy, benefit sharing etc. By additionally highlighting the widely neglected aspect of trust, this book aims at broadening the horizon of the ELSI-debate and thus filling a gap in current research on biobanking. The contributions of leading experts and junior researchers cover a wide field of disciplines relevant for biobanking including law, ethics, medicine, public health, social sciences, philosophy and theology.

OBJECTIVES: Newborn screening (NBS) programs may store bloodspot samples and use them for secondary purposes. Recent public controversies and lawsuits over storage and secondary uses underscore the need to engage the public on these issues. We explored Canadian values regarding storage and use of NBS samples for various purposes and the forms of parental choice for anonymous research with NBS samples. METHODS: We conducted a mixed-methods, public engagement study comprising 8 focus groups (n = 60), an educational component, deliberative discussion, and pre- and post-questionnaires assessing knowledge and values toward storage and parental choice. RESULTS: Canadian citizens supported the storage of NBS samples for quality control, confirmatory diagnosis, and future anonymous research (>90%). There was broad support for use of NBS samples for anonymous research; however, opinions were split about the extent of parental decision-making. Support for a “routinized” approach rested on trust in authorities, lack of concern for harms, and an assertion that the population’s interest took priority over the interests of individuals. Discomfort stemmed from distrust in authorities, concern for harms, and prioritizing individual interests, which supported more substantive parental choice. Consensus emerged regarding the need for greater transparency about the storage and secondary use of samples. CONCLUSIONS: Our study provides novel insights into the values that underpin citizens’ acceptance and discomfort with routine storage of NBS samples for research, and supports the need to develop well-designed methods of public education and civic discourse on the risks and benefits of the retention and secondary use of NBS samples.

Membrane transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are efflux pumps that remove drugs from the brain back to the peripheral blood compartment, serving as a functional component of the blood-brain barrier (BBB). We report here that coadministration of the P-gp and BCRP inhibitor ketoconazole with risperidone may preferentially increase D2 receptor occupancy in the striatum compared to pituitary. Four male patients with schizophrenia or schizoaffective disorder who had received at least 4 prior injections of the long-acting risperidone at a stable dose of 25 to 50 mg participated in this positron emission tomography study. Multiple-dose ketoconazole coadministration reduced the P-gp activity as shown by fexofenadine oral challenge. Importantly, we found a strong statistical trend in this sample of 4 subjects who consistently showed a decrease in striatal fluorine 18 (F)-fallypride binding (an indication of increased D2 receptor occupancy) after ketoconazole coadministration (P = 0.057), whereas the pituitary (a region that lies outside the BBB) F-fallypride binding did not change (P = 0.99). These observations warrant further research with selective drug transporter inhibitors. We suggest that in neuroimaging studies, the pituitary drug occupancy can serve as a useful new "positive control" to evaluate whether drug occupancy is preferentially increased in brain regions that fall inside the BBB after cotreatment with P-gp and BCRP inhibitors. This is a noteworthy study design consideration regarding the future clinical testing of novel adjunct interventions aimed at modulating membrane transporter function at the BBB, with the goal of augmenting drug access into the brain compartment, particularly in treatment-resistant psychiatric illness.

Ma’n H Zawati, 2012 6-1 Revue de droit et santé de McGill 137, 2012 CanLIIDocs 24

The past year has been one of great change and achievement for the Canadian stem cell community.

Stem cell repositories, similar to many areas in human scientific research, must balance the interests of the individuals who donate their time and samples to science with the interests of scientific progress. This article seeks to explore how sustained interaction with stem cell donors can advance key donor interests (autonomy and privacy) while also increasing the scientific utility of stem cell lines. The ability to trace stem cell lines to their respective donors – underpinned by robust informed consent – enables donors to gain access to information regarding research outcomes and the uses of their biological samples, while also supporting basic and clinical research by providing a means for quality and safety controls. Measures to recontact donors and also to enable donors to withdraw from research should be well designed to ensure donors’ preferences are respected while mitigating negative consequences resulting from limited data availability or compromised sample quality. To guarantee the integrity of research while respecting donors’ autonomy and preferences, stem cell repositories require a prospective approach to informed consent.

The ability to share human biological samples, associated data and results across disease-specific and population-based human research biobanks is becoming increasingly important for research into disease development and translation. Although informed consent often does not anticipate such cross-domain sharing, it is important to examine its plausibility. The purpose of this study was to explore the feasibility of bridging consent between disease-specific and population-based research. Comparative analyses of 1) current ethical and legal frameworks governing consent and 2) informed consent models found in disease-specific and population-based research were conducted.

Large-scale, public genomic databases have greatly improved the capacity of researchers to do genomic research. In order to ensure that the scientific community uses data from these public resources properly, data access agreements have been developed to complement already existing legal and ethical norms. Sanctions to address cases of data misuse constitute an essential part of this compliance framework meant to protect stakeholders in genomic research. Yet very little research and community debate has been done on this most important topic. This paper presents a review of different sanctions that could be invoked in cases of non-compliance from data users. They have been identified through comprehensive research and analysis of over 450 documents (journal articles, policy, guidelines, access policies, etc.) related to this topic. Given the considerable impact on users of even the milder sanctions considered in our paper, it is essential that stakeholders strive to achieve the highest degree of standardization and transparency when designing controlled-access agreements. It is only fair, after all, that users be able to expect that the border between acceptable and unacceptable conduct is clearly delineated and predictable in controlled-access policies. This suggests the importance for researchers to undertake additional empirical studies on the clarity and accessibility of existing database access agreements and related policies in the near future.

High-throughput sequencing technology enables population-level surveys of human genomic variation. Here, we examine the joint allele frequency distributions across continental human populations and present an approach for combining complementary aspects of whole-genome, low-coverage data and targeted high-coverage data. We apply this approach to data generated by the pilot phase of the Thousand Genomes Project, including whole-genome 2–4× coverage data for 179 samples from HapMap European, Asian, and African panels as well as high-coverage target sequencing of the exons of 800 genes from 697 individuals in seven populations. We use the site frequency spectra obtained from these data to infer demographic parameters for an Out-of-Africa model for populations of African, European, and Asian descent and to predict, by a jackknife-based approach, the amount of genetic diversity that will be discovered as sample sizes are increased. We predict that the number of discovered nonsynonymous coding variants will reach 100,000 in each population after ∼1,000 sequenced chromosomes per population, whereas ∼2,500 chromosomes will be needed for the same number of synonymous variants. Beyond this point, the number of segregating sites in the European and Asian panel populations is expected to overcome that of the African panel because of faster recent population growth. Overall, we find that the majority of human genomic variable sites are rare and exhibit little sharing among diverged populations. Our results emphasize that replication of disease association for specific rare genetic variants across diverged populations must overcome both reduced statistical power because of rarity and higher population divergence.

Data sharing is increasingly regarded as an ethical and scientific imperative that advances knowledge and thereby respects the contributions of the participants. Because of this and the ever-increasing amount of data access requests currently filed around the world, three groups have decided to develop data sharing principles specific to the context of collaborative international genomics research. These groups are: the international Public Population Project in Genomics (P3G), an international consortium of projects partaking in large-scale genetic epidemiological studies and biobanks; the European Network for Genetic and Genomic Epidemiology (ENGAGE), a research project aiming to translate data from large-scale epidemiological research initiatives into relevant clinical information; and the Centre for Health, Law and Emerging Technologies (HeLEX). We propose seven different principles and a preliminary international data sharing Code of Conduct for ongoing discussion.

Matthew Hurles and colleagues report the first direct comparative analysis of male and female germline mutation rates from whole-genome sequences of two parent-offspring trios sequenced as part of the 1000 Genomes Project. They identify variation in paternal and maternal mutation rates between these two families.

Although the scientific research surrounding pharmacogenomics (PGx) has been relatively plentiful, the ethical research concerning this discipline has developed rather conservatively. Following investigation of the ethical, legal and social issues (ELSI) of PGx research, as well as consulting with key stakeholders, we identified six outstanding ethical issues raised by the informed consent process in PGx research: (1) scope of consent; (2) consent to ‘add-on’ studies; (3) protection of personal information; (4) commercialization; (5) data sharing; and (6) potential risks stemming from population-based research. In discussing these six areas as well as offering specific considerations, this article offers a solid base from which future practical guidelines for informed consent in PGx research can be constructed. As such, this effort works toward filling the ELSI gap and provides ethical support to the numerous PGx projects undertaken by researchers every year.

If the 2010 CPHA conference is a bellwether of mainstream Canadian public and global health practice, its dearth of human rights papers suggests that, outside a small scholarly cohort, human rights remain marginal therein. This potential ‘rights gap’ conflicts with growing recognition of the relationship between health and human rights and ergo, the importance of human rights education for health professionals. This gap not only places Canadian health research outside the growing vanguard of academic research on health and human rights, but also ignores a potentially influential tool for achieving health equity. I suggest that human rights make a distinctive contribution to such efforts not replicated within other social justice and equity approaches, making human rights education a crucial complement to other ethical training. These contributions are evident in the normative specificity of the right to health in international law and its legally binding nature, in the success of litigation, the successful advocacy for AIDS treatment and the growing adoption of rights-based approaches to health. Canadian academic and research institutions should take up their rightful place within health and human rights research, education and practice globally, including by ramping up human rights-oriented education for health professionals within Canadian universities.

In 2009, Time magazine named “biobanks” as one of the 10 ideas changing the world. These organized collections of human biological material and associated data have been identified as “vital research tools in the drive to uncover the consequences of human health and disease.” Since their inception, however, biobanks have faced ethical and legal challenges. Whether these pertain to informed consent, access by researchers, commercialization, confidentiality, or governance, biobanks must continue to address jurisdictional matters, operational difficulties, and normative frameworks that strive to stay abreast of current scientific innovation. Yet, with some biobanks now having completed their recruitment objectives and with research currently being performed on their data and samples, one topic has become the focus of ongoing debates: the return of research results to participants.

Until the mid-20th century, biomedical research centered on the study of specific diseases, concerned with short periods of time and small groups of living research participants. However, the growth of longitudinal population studies and long-term biobanking now forces the research community to examine the possibility of the death of their research participants. The death of a research participant raises numerous ethical and legal issues, including the return of deceased individuals’ research results to related family members. As with the return of individual research results for living research participants, the question of the obligation to return a deceased person’s research results to family members has yet to be settled. This question is particularly acute in the context of genetic research since the research results from one individual may have health implications for all biological relatives.

Stem cell banks are increasingly recognized as an essential resource of biological materials for both basic and translational stem cell research. By providing transnational access to quality controlled and ethically sourced stem cell lines, stem cell banks seek to foster international collaboration and innovation. However, given that national stem cell banks operate under different policy, regulatory and commercial frameworks, the transnational sharing of stem cell materials and data can be complicating. This paper will provide an overview of the most pressing challenges regarding the governance of stem cell banks, and the difficulties in designing regulatory and commercial frameworks that foster stem cell research. Moreover, the paper will shed light on the numerous international initiatives that have arisen to help harmonize and standardize stem cell banking and research processes to overcome such challenges.

As a matter of respect for the person, it is considered an ethical duty to offer to return research results to participants where appropriate. Nevertheless, the return of individual research results to participants raises many socio-ethical issues and greater challenges when the participant is a child. This discrepancy arises partly because the return of individual pediatric research results entails a tripartite relationship between researcher, child, and parent(s) and is embroiled in numerous considerations (e.g., acting in the best interest of the child, respect for the person, and respect for the autonomy of the parents/child). Extra caution is required in the pediatric research context because children cannot generally decide (consent) whether they want to be informed of their own research results or whether the results should be disclosed to parents. Children have long been considered a special and vulnerable group, and their parents, as guardians, play a critical role in the consent process. However, with regards to the return of individual research results, this might pose a potential conflict of interest between the current or future desires of the child and those of the parents.

Emmanuelle Lévesque, Bartha Maria Knoppers, 2011 5-2 Revue de droit et santé de McGill 163, 2011 CanLIIDocs 7

Five years ago, an article co-written by some of us (Joly and Simard) presented an emerging trend to disclose some individual genetic results to research participants within the international research community. At the time, ethical norms and scholarly publications on the return of results often did not distinguish between the return of research results in general and the return of unexpected results (also called incidental findings). Both technologies and research practices have evolved significantly. Today whole genome and exome sequencing are increasingly affordable and frequently used in genetic research. Because these techniques produce a vast amount of interpretable and non-interpretable data (i.e., data of unproven significance) about an individual, the issue of how to manage information generated by such technologies needs to be considered. However, the development of international ethical guidelines has not kept up with the rapid pace of technological progress. Indeed developments in genomic biobanking also challenge the duty to disclose research results.

The last few years have witnessed the growth of large-scale, population genomics biobanks, which serve as longitudinal, gene-environment databases for future yet unspecified research. An international consortium, the Public Population Project in Genomics (P3G), builds harmonization tools for such biobanks and has catalogued numerous studies — at least 139 with over 10,000 banked participants and 34 with over 100,000. As their potential use for translational, clinical research draws near, it is opportune to clarify the duties of such biobanks to communicate results to participants. To identify the potential obligations, some demystification of the terminology surrounding the return of results as found in international and national norms on biobanking generally is essential. On the whole, our proposed lexicon is based on a study of norms as found in national and international policies but excludes debates found in the literature.

In recent years, the research participant’s family’s need, if not right, to know their disease risk has comprised a great deal of the genetic testing discourse. This most often arises in the context of clinical genetic tests for hereditary cancers, especially colorectal and breast cancer, and other genetic disorders where the presence of a genetic mutation greatly increases the likelihood of the disease’s manifestation (such as Huntington’s Disease). However, this discussion has not led to comprehensive or cohesive guidance for health care professionals or patients. Indeed, various governmental and professional bodies run the gamut of possibilities, from no disclosure to family without the consent of the patient, to recognition that genetic risk information is important enough to the family to allow exception to traditional notions of confidentiality.

In this brief investigation, the informational needs of research participants [n = 62; mothers who had breastfed, taken codeine, and participated in a pharmacogenetic study] were probed during a counselling session in which they received their CYP2D6 pharmacogenetic research results and overall study results. In addition to the standard information, developed by a multidisciplinary team and provided to the participants, 38% of individuals had further questions related to potential adverse effects in babies, future codeine or medication use, heredity, and consequences for policies and programmes. The diversity and complexity of the questions raised support the need to communicate the results in the context of personalized genetic counselling information sessions.

Pharmacogenomics is the study of how genetic variants affect the way in which an individual or subgroup responds to drugs. This developing field aims to inform individual drug therapy and to minimize adverse drug reactions (ADRs). It also promises great benefits in the drug development process. Innovation in pharmacogenomics and its translation into clinical practice is desirable, but appropriate regulation of the safety and effectiveness of pharmacogenomics testing is necessary. This article will describe the current regulatory framework applicable to pharmacogenomic tests in Canada, the United States and Europe. In particular, it will examine the different regulatory pathways for pharmacogenomic tests marketed as test kits and for laboratory-developed tests (LDTs). Recent and upcoming changes to the regulation of pharmacogenomic tests will also be discussed. For example, FDA's proposal to regulate LDTs could have a major impact on the development and availability of pharmacogenomic tests. This review will lead to an evaluation of the issues raised by the regulatory framework and the impact of regulatory changes in relation to meeting the goals of ensuring public safety and promoting the advancement of pharmacogenomics. Regulatory policies which successfully achieve the dual objectives of ensuring public safety and promoting innovation in health technology are imperative in order to reap the benefits of this emerging field.

Discussion and output from the US FDA and the pharmaceutical industry from the Drug Information Association/FDA 5th Workshop in a series on pharmacogenomics entitled: ‘Generating and Weighing Evidence in Drug Development and Regulatory Decision Making’. A major topic area at the 5th FDA/Industry Workshop on Pharmacogenomics, February 2–4, 2010 in Bethseda (MD, USA), was enabling pharmacogenomic clinical trials through collection of future use samples. The importance of the collection of samples with permission for future analyses was affirmed by both industry and the FDA. In addition, current barriers for the collection of such samples were detailed and possible solutions for overcoming barriers at sites, as well as globally within countries, were discussed. The importance of international concordance on collection of these samples was emphasized, and potential areas for industry to harmonize sample collection practices. A standalone workshop on issues related to sampling was determined to be a key step for solving issues related to future use sample collection during drug development.

The commercialization of academic research has been promoted by North American policy makers for over 30 years as a means of increasing university financing and to ensure that promising research would eventually find its way to the marketplace. The following issues paper constitutes a reflection on the impact of the Canadian commercialization framework on academic research in the field of genomics. It was written following two workshops and two independent studies organized by academic groups in Quebec (Centre of Genomics and Policy) and Alberta (Health Law Institute). The full sets of recommendations are available upon request to the authors.

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother–father–child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10−8 per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

Open biotechnology may be the ideal solution to ensure scientific progress and the realization of the common good, but it has yet to deliver on its promises.

Hundreds of individual human cancer genome sequences are expected to be published in 2010, and thousands per year after that. The International Cancer Genome Consortium (ICGC) was launched with the aim of keeping track of the data relating to large-scale cancer genome studies of all major cancers in adults and children — a total of 50 different cancer types and/or subtypes. In this issue the ICGC team (http://www.icgc.org) spells out the policies and planning for the project.

More and more companies are advertising and selling genetic tests directly to consumers. Considering the ethical, legal, and psychological concerns surrounding genetic testing in minors, a study of companies’ websites was performed in order to describe and analyze their policies with respect to this issue. Of the 29 companies analyzed, 13 did not provide any information about this matter, eight companies allowed genetic testing upon parental request, four companies stated that their website is not directed to children under 18 years, and four companies suggested that in order to be tested, applicants should have reached the age of legal majority. If private companies offer genetic tests which are also offered in a clinical setting, can they be expected to adhere to the existing clinical guidelines with regard to these tests? If so, a certain ambiguity exists. Many companies are emphasizing in their disclaimers that their services are not medical services and should not be used as a basis for making medical decisions. Nonetheless, it remains debatable whether genetic testing in minors would be appropriate in this context. In line with the Advisory Committee on Genetic Testing, the Human Genetics Commission addressed the problem of non-consensual testing and recommended not to supply genetic testing services directly to those under the age of 16 or to those not able to make a competent decision regarding testing.

The advent of both population genomic studies and direct-to-consumer personal genetic testing raises ethical challenges for researchers and physicians alike. Quality and solidarity can now be added to traditional ethical principles, such as autonomy and privacy. There is no doubt that genetic information is going 'public'. Informatic technologies allow for greater accessibility and integration, but can researchers and physicians handle the challenges? Are ethics committees equipped to handle this shift towards greater openness and towards a conflation of research and traditional medical ethics?

De plus en plus, la recherche en génétique s’attarde à identifier les mutations de gènes qui prédisposent les porteurs de ces mutations à des maladies complexes. La recherche tente également d’établir un lien entre le développement de la maladie pour certains porteurs en fonction de leur contexte socio-économique et de leur interaction avec l’environnement. Compte tenu de ces nombreux facteurs d’analyse, l’interprétation des caractéristiques génétiques d’un individu et du risque qui en découle s’avère particulièrement complexe. Or, cette complexité croissante se produit alors même que l’accès aux données génétiques se banalise et qu’il est maintenant possible pour quiconque d’obtenir une analyse personnalisée de son génome via l’internet. La discrimination génétique n’est pas définie en droit canadien ; il est généralement acquis que, dans le contexte de l’assurance-vie, celle-ci est susceptible d’avoir des conséquences désastreuses. Cependant, nous ne croyons pas que l’information d’ordre génétique doive être l’objet d’une approche exceptionnelle causant accrocs au droit général des assurances. D’autant plus, les conséquences du risque de discrimination génétique semblent davantage relevées de la crainte que de l’exercice d’une discrimination réelle. Dans ce contexte, il s’avère nécessaire d’évaluer les mesures de protection contre la discrimination génétique dans le contexte de l’assurance-vie. Pour ce faire, nous abordons, d’une part, les normes d’application générale en matière de protection contre la discrimination; normes parmi lesquelles la Charte des droits et libertés de la personne offre une protection intéressante. D’autre part, nous nous intéressons aux normes visant la discrimination spécifiquement génétique, notamment le nouvel Genetic Information Nondiscrimination Act et l’affaire Audet c. Industrielle-Alliance. Enfin, nous proposons des mesures minimales qui sauraient s’avérer utile pour préserver un juste équilibre.

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Rapid release of prepublication data has served the field of genomics well. Attendees at a workshop in Toronto recommend extending the practice to other biological data sets.

Access to samples and individual DNA sequence data from children included in population biobanks should, when feasible, await their consent as adults. , Population biobanks, which store and distribute human DNA, cell lines, and tissue samples collected from large cohorts, are being established and are growing in size ( 1 ). These population biobanks are often funded wholly or in part by governments and are envisaged as novel resources for national and international biomedical research programs. Such programs include studies on associations between genotypes, environmental exposure measures, socioeconomic parameters, and phenotypes of human health and disease.