Challenges of Genetic Data Sharing in African Studies.

Data sharing is a valuable aspect of science and required by most funding bodies and journals. However, the national regulatory guidelines of many African nations do not explicitly allow for broad genetic data sharing. Given these restrictions, there is a need to reconsider these policies and propose creative solutions.

Comparative Approaches to Genetic Discrimination: Chasing Shadows?

Genetic discrimination (GD) is one of the most pervasive issues associated with genetic research and its large-scale implementation. An increasing number of countries have adopted public policies to address this issue. Our research presents a worldwide comparative review and typology of these approaches. We conclude with suggestions for public policy development.

Do patients and research subjects have a right to receive their genomic raw data? An ethical and legal analysis.

BACKGROUND: As Next Generation Sequencing technologies are increasingly implemented in biomedical research and (translational) care, the number of study participants and patients who ask for release of their genomic raw data is set to increase. This raises the question whether research participants and patients have a legal and moral right to receive their genomic raw data and, if so, how this right should be implemented into practice. METHODS: In a first step we clarify some central concepts such as "raw data"; in a second step we sketch the international legal framework. The third step provides an extensive ethical analysis which comprehends two parts: an evaluation of whether there is a prima facie moral right to receive one's raw data, and a contextualization and discussion of the right in light of potentially conflicting interests and rights of the data subject herself and third parties; in a last fourth step we emphasize the main practical consequences of the ethical analyses and propose recommendations for the release of raw data. RESULTS: In several legislations like the new European General Data Protection Regulation, patients do in principle have the right to receive their raw data. However, the procedural implementation of this right and whether it involves genetic counselling is at the discretion of the Member States. Even more questions remain with respect to the research context. The ethical analysis suggests that patients and research subjects have a moral right to receive their genomic raw data and addresses aspects which are also of relevance for the legal discussion such as the costs of release of raw data and its impact on academic freedom. CONCLUSION: Taking into account the specific nature and implications of genomic raw data and the contexts of research and health care, several concerns and potentially conflicting interests of the data subjects themselves and involved researchers, physicians, biomedical institutions and relatives arise. Instead of using them to argue in favor of restrictions of the data subjects' legal and moral right to genomic raw data, the concerns should be addressed through provision of information and other measures. To this end, we propose relevant recommendations.

Genetic research and consent: On the crossroads of human and data research.

This paper explores the legal and ethical concept of human subject research in order to determine whether genetic research with already available biosamples and data falls within this concept. Although the ethical concept seems to have evolved to recognize research based on data as human research, from a supranational legal perspective this form of research is not considered human subject research. Thus human subject research regulations do not apply and therefore do not invoke the requirement of obtaining consent prior to using an individual's biosample or genetic data in research. Furthermore, it remains ambiguous in both the legal and ethical realm whether the use of biosamples or genetic data without additional links to the individual would invoke the same safeguards as research involving additional or specific identifiers. Seeing that research based on already available biosamples and genetic data is not governed by rules concerning human subject research, the second part of the paper analyses whether any consent requirements apply for the further use of already available bio-samples or genetic data in research. Whereas further use of biosamples is subject to considerably lax consent requirements under Article 22 of the Oviedo Convention, under the General Data Protection Regulation further use of genetic data might not be subject to a prior consent requirement at all, unless it is stipulated in national laws. When it comes to clinical trials, however, sponsors will have the possibility under Article 28(2) of Regulation 536/2014 to obtain open consent for further use of data in any kind of future research.

Germany: a fair balance between scientific freedom and data subjects' rights?

With the German Bundestag's adoption of the Data Protection Adaptation and Implementation Act EU (DSAnpUG-EU) on 30 June 2017, the adaptation of German law to the General Data Protection Regulation (GDPR) has begun (Gesetz zur Anpassung des Datenschutzrechts an die Verordnung (EU) 2016/679 und zur Umsetzung der Richtlinie (EU) 2016/680 (Datenschutz-Anpassungs- und -Umsetzungsgesetz-DSAnpUG-EU) v. 30. Juni 2017, BGBl. 2017 I p. 2097 et seq.). Despite being directly binding on all EU member states, the GDPR does not render national data protection provision obsolete-they are covered by the GDPR's opening clauses which include regulatory mandates and room for derogation. This creates considerable need for national legislative adaptation. Art. 1 DSAnpUG-EU contains the necessary amendments to the Federal Data Protection Law (BDSG(neu)), thus creating the second major building block of future German data protection alongside the GDPR itself. Nevertheless, there are still numerous sector-specific regulations in other federal laws and the data protection laws of the 16 states also need amendments. Adjustment in Germany is well on its way, but implementation in general is still ongoing, with further consequences for data processing and sharing.

Australia: regulating genomic data sharing to promote public trust.

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

United Kingdom: transfers of genomic data to third countries.

In the United Kingdom (UK), transfer of genomic data to third countries is regulated by data protection legislation. This is a composite of domestic and European Union (EU) law, with EU law to be adopted as domestic law when Brexit takes place. In this paper we consider the content of data protection legislation and the likely impact of Brexit on transfers of genomic data from the UK to other countries. We examine the advice by regulators not to rely upon consent as a lawful basis for processing under data protection law, at least not when personal data are used for research purposes, and consider some of the other ways in which the research context can qualify an individual's ability to exercise control over processing operations. We explain how the process of pseudonymization is to be understood in the context of transfer of genomic data to third parties, as well as how adequacy of data protection in a third country is to be determined in general terms. We conclude with reflections on the future direction of UK data protection law post Brexit with the reclassification of the UK itself as a third country.

China: concurring regulation of cross-border genomic data sharing for statist control and individual protection.

This paper reviews the major legal instruments and self-regulations that bear heavily on the cross-border sharing of genomic data in China. It first maps out three overlapping frameworks on genomic data and analyzes their underpinning policy goals. Subsequent sections examine the regulatory approaches with respect to five aspects of responsible use and sharing of genomic data, namely, consent, privacy, security, compatible processing, and oversight. It argues that substantial centralised control exerted by the state is, and would probably remain, the dominant feature of genomic data governance in China, though concerns of individual protection are gaining momentum. Rather than revolving around a simplistic antinomy between privacy preservation and open science, the regulatory landscape is mainly shaped by the tension between government desires for national security, state competitiveness, and public health benefits.

Canada: will privacy rules continue to favour open science?

Canada's regulatory frameworks governing privacy and research are generally permissive of genomic data sharing, though they may soon be tightened in response to public concerns over commercial data handling practices and the strengthening of influential European privacy laws. Regulation can seem complex and uncertain, in part because of the constitutional division of power between federal and provincial governments over both privacy and health care. Broad consent is commonly practiced in genomic research, but without explicit regulatory recognition, it is often scrutinized by research or privacy oversight bodies. Secondary use of health-care data is legally permissible under limited circumstances. A new federal law prohibits genetic discrimination, but is subject to a constitutional challenge. Privacy laws require security safeguards proportionate to the data sensitivity, including breach notification. Special categories of data are not defined a priori. With some exceptions, Canadian researchers are permitted to share personal information internationally but are held accountable for safeguarding the privacy and security of these data. Cloud computing to store and share large scale data sets is permitted, if shared responsibilities for access, responsible use, and security are carefully articulated. For the moment, Canada's commercial sector is recognized as "adequate" by Europe, facilitating import of European data. Maintaining adequacy status under the new European General Data Protection Regulation (GDPR) is a concern because of Canada's weaker individual rights, privacy protections, and regulatory enforcement. Researchers must stay attuned to shifting international and national regulations to ensure a sustainable future for responsible genomic data sharing.

Authorization of tissues from deceased patients for genetic research.

Tissues from deceased donors provide important data for genomic research and Organ Procurement Organizations (OPOs) play a significant role. To understand the decisions of families who donated for transplantation and made decisions about donation to the Genotype-Tissue Expression Project (GTEx), we examined donation decisions of family decision makers (FDMs). 413 families were interviewed by telephone. The OPO staff who made the transplant and research requests completed self-administered surveys; a total of 309 matching surveys from 99 OPO staff were obtained. 76.8% of families donated to the GTEx project. Logistic regression analysis found that FDM consent to GTEx donation was associated with endorsement of policies to promote biobanking (OR = 1.35), positive attitudes about medical research (OR = 1.1), lack of concern regarding a breach of confidentiality (OR = 1.54), comfort with tissue donation (OR = 1.24), and prior authorization to solid organ donation (OR = 3.17). OPO staff characteristics associated with GTEx donation included being female (OR = 3.57), White (OR = 4.97), comfort with hospital staff role in donation (OR = 1.61), and number of topics discussed with families (OR = 57.9). Donor type, FDM attitudes, OPO staff sociodemographics, OPO comfort with the GTEx authorization process, and intensity of discussing research-specific issues were significantly associated with GTEx donation decisions.

Conclusion: harmonisation in genomic and health data sharing for research: an impossible dream?

There are clear benefits from genomics and health data sharing in research and in therapy for individuals across societies. At the same time, citizens have different expectations and fears about that data sharing. International legislation in relation with research ethics and practice and, particularly, data protection create a particular environment that, as is seen in the articles in part two of this special issue, are crying out for harmonisation both at a procedural but at fundamental conceptual levels. The law of data sharing is pulling in different directions. This paper poses the question, 'harmonisation, an impossible dream?' and the answer is a qualified 'no'. The paper reflects on what can be seen in the papers in part two of the special issue. It then identifies three major areas of conceptual uncertainty in the new EU General Data Protection Regulation (not because it has superiority over other jurisdictions, but because it is a recent revision of data protection law that leaves universal conceptual questions unclear). Thereafter, the potential for Artificial Intelligence to meet some of the shortcomings is discussed. The paper ends with a consideration of the conditions under which data sharing harmonisation might be achieved: an understanding of a human rights approach and citizen sensitivities in considering the 'public interest'; social liberalism as a basis of solidarity; and the profession of 'researcher'.

United States: law and policy concerning transfer of genomic data to third countries.

This paper provides an overview of US laws and related guidance documents affecting transfer of genomic data to third countries, addressing the domains of consent, privacy, security, compatible processing/adequacy, and oversight. In general, US laws governing research and disclosure and use of data generated within the health care system do not impose different requirements on transfers to researchers and service providers based in third countries compared with US-based researchers or service providers. Of note, the US lacks a comprehensive data protection regime. Data protections are piecemeal, spread across bodies of law that target specific kinds of research or data generated or held by specific kinds of actors involved in the delivery of health care. Oversight is also distributed across a range of bodies, including institutional review boards and data access committees. The conclusion to this paper examines future directions in US law and policy, including proposals for more comprehensive protections for personal data.

Patenting Foundational Technologies: Lessons From CRISPR and Other Core Biotechnologies.

In 2012, a new and promising gene manipulation technique, CRISPR-Cas9, was announced that seems likely to be a foundational technique in health care and agriculture. However, patents have been granted. As with other technological developments, there are concerns of social justice regarding inequalities in access. Given the technologies' "foundational" nature and societal impact, it is vital for such concerns to be translated into workable recommendations for policymakers and legislators. Colin Farrelly has proposed a moral justification for the use of patents to speed up the arrival of technology by encouraging innovation and investment. While sympathetic to his argument, this article highlights a number of problems. By examining the role of patents in CRISPR and in two previous foundational technologies, we make some recommendations for realistic and workable guidelines for patenting and licensing.

Returning Results to Family Members: Professional Duties in Genomics Research in the United States.

 This article critically appraises the ethical and legal duties to disclose findings to the family members of research participants. These family members stand to benefit in important ways from discoveries that can inform their own health and reproductive risks. However, careful appreciation of how medical research differs from clinical practice and of the uncertainties at stake in genomic research complicates any warning to relatives. Research laboratories should generally be immune from liability for failing to diagnose or disclose a genetic disorder in time to prevent adverse outcomes for a participant's family members or to return properly interpreted test results for even direct findings under investigation, let alone incidental ones. The only exception is where warning relatives of medical risks is very likely to prevent imminent harm and would not override known participant wishes. Genomic autopsy studies for sudden death satisfy these conditions of life-saving potential for relatives without disrespect to subjects. These are among the rare instances in which we conclude that offering results to family members is not just permissible but obligatory, not just as a moral matter but as a legal one.

Explanation of the Nagoya Protocol on Access and Benefit Sharing and its implication for microbiology.

Working with genetic resources and associated data requires greater attention since the Nagoya Protocol on Access and Benefit Sharing (ABS) came into force in October 2014. Biologists must ensure that they have legal clarity in how they can and cannot use the genetic resources on which they carry out research. Not only must they work within the spirit in the Convention on Biological Diversity (https://www.cbd.int/convention/articles/default.shtml?a=cbd-02) but also they may have regulatory requirements to meet. Although the Nagoya Protocol was negotiated and agreed globally, it is the responsibility of each country that ratifies it to introduce their individual implementing procedures and practices. Many countries in Europe, such as the UK, have chosen not to put access controls in place at this time, but others already have laws enacted providing ABS measures under the Convention on Biological Diversity or specifically to implement the Nagoya Protocol. Access legislation is in place in many countries and information on this can be found at the ABS Clearing House (https://absch.cbd.int/). For example, Brazil, although not a Party to the Nagoya Protocol at the time of writing, has Law 13.123 which entered into force on 17 November 2015, regulated by Decree 8.772 which was published on 11 May 2016. In this case, export of Brazilian genetic resources is not allowed unless the collector is registered in the National System for Genetic Heritage and Associated Traditional Knowledge Management (SisGen). The process entails that a foreign scientist must first of all be registered working with someone in Brazil and have authorization to collect. The enactment of European Union Regulation po. 511/2014 implements Nagoya Protocol elements that govern compliance measures for users and offers the opportunity to demonstrate due diligence in sourcing their organisms by selecting from holdings of 'registered collections'. The UK has introduced a Statutory Instrument that puts in place enforcement measures within the UK to implement this European Union Regulation; this is regulated by Regulatory Delivery, Department for Business, Energy and Industrial Strategies. Scientific communities, including the private sector, individual institutions and organizations, have begun to design policy and best practices for compliance. Microbiologists and culture collections alike need to be aware of the legislation of the source country of the materials they use and put in place best practices for compliance; such best practice has been drafted by the Microbial Resource Research Infrastructure, and other research communities such as the Consortium of European Taxonomic Facilities, the Global Genome Biodiversity Network and the International Organisation for Biological Control have published best practice and/or codes of conduct to ensure legitimate exchange and use of genetic resources.

Pathogenic variants in the healthy elderly: unique ethical and practical challenges.

: Genetic research into ageing, longevity and late-onset disease is becoming increasingly common. Yet, there is a paucity of knowledge related to clinical actionability and the return of pathogenic variants to otherwise healthy elderly individuals. Whether or not genetic research in the elderly should be managed differently from standard practices adapted for younger populations has not yet been defined. In this article, we provide an overview of ethical and practical challenges in preparing for a genetic study of over 14 000 healthy Australians aged 70 years or older enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) Healthy Ageing Biobank. At the time of consent, all participants in this study were free of life-threatening illness, cardiovascular disease or cognitive impairment. ASPREE is thus a cohort of healthy elderly individuals with seemingly minimal burden of genetic disease recruited without ascertainment bias. The cohort presents a unique opportunity to address the penetrance of known pathogenic variants in a population without disease symptoms; however, it also raises a number of ethical concerns regarding the interpretation and disclosure of variants with known clinical actionability. Some of the challenges include (a) how to manage the interpretation, disclosure and actioning of pathogenic variants found in otherwise healthy elderly adults without disease symptoms, (b) whether or not to disclose findings for the benefit of family members rather than elderly consented donors themselves, (c) how to manage the return of genetic findings to the elderly individuals who are now in severe cognitive decline or terminal illness, (d) how to ensure quality of information and clinical service upon disclosure of results to this demographic and (e) how to prepare for the insurance implications of disclosing genetic information under Australian law. We discuss these and other dilemmas and propose a defensible plan of management. TRIAL REGISTRATION NUMBER: ISRCTN83772183.

Obtaining informed consent for genomics research in Africa: analysis of H3Africa consent documents.

BACKGROUND: The rise in genomic and biobanking research worldwide has led to the development of different informed consent models for use in such research. This study analyses consent documents used by investigators in the H3Africa (Human Heredity and Health in Africa) Consortium. METHODS: A qualitative method for text analysis was used to analyse consent documents used in the collection of samples and data in H3Africa projects. Thematic domains included type of consent model, explanations of genetics/genomics, data sharing and feedback of test results. RESULTS: Informed consent documents for 13 of the 19 H3Africa projects were analysed. Seven projects used broad consent, five projects used tiered consent and one used specific consent. Genetics was mostly explained in terms of inherited characteristics, heredity and health, genes and disease causation, or disease susceptibility. Only one project made provisions for the feedback of individual genetic results. CONCLUSION: H3Africa research makes use of three consent models-specific, tiered and broad consent. We outlined different strategies used by H3Africa investigators to explain concepts in genomics to potential research participants. To further ensure that the decision to participate in genomic research is informed and meaningful, we recommend that innovative approaches to the informed consent process be developed, preferably in consultation with research participants, research ethics committees and researchers in Africa.

Potential International Approaches to Ownership/Control of Human Genetic Resources.

In its governance activities for genetic resources, the international community has adopted various approaches to their ownership, including: free access; common heritage of mankind; intellectual property rights; and state sovereign rights. They have also created systems which combine elements of these approaches. While governance of plant and animal genetic resources is well-established internationally, there has not yet been a clear approach selected for human genetic resources. Based on assessment of the goals which international governance of human genetic resources ought to serve, and the implications for how they will be accessed and utilised, it is argued that common heritage of mankind will be the most appropriate approach to adopt to their ownership/control. It does this with the aim of stimulating discussion in this area and providing a starting point for deeper consideration of how a common heritage of mankind, or similar, regime for human genetic resources would function and be implemented.