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A collegial procedure refers to the fact that, before making a delicate medical decision, the opinion of the entire care team responsible for the patient is sought, including nurses and orderlies, among others. The Claeys-Leonetti end-of-life law (2016) enshrines this in French law as mandatory when implementing deep and continuous sedation until death (DCSD). The aim of the study was to take stock of the awareness of this aspect of the law among all the healthcare staff of a cancer institute and to identify how collegiality was established for a DCSD decision, depending on the department. We administered an anonymous online questionnaire to all those involved in healthcare (knowledge of the Claeys-Leonetti Act), and then met healthcare workers from the various departments in discussion groups (managers, nursing staff and orderlies) or in individual interviews (doctors). The results show that young healthcare staff (with less than 5 years’ experience) are more familiar with the law, across all professions, and that nurses and orderlies are more likely to assert their rights than doctors. We report on the diversity of the implementation of collegiality for sedation decisions, in terms of formalisation, standardisation and inter-professionalisation. We conclude that the implementation of collegiality in advance of a decision broadens the methods of multi/inter-professional communication and helps to alleviate the suffering of patients, doctors and care givers., Une procédure collégiale désigne le fait de recueillir, avant de prendre une décision médicale délicate, l’avis de l’ensemble de l’équipe de soins responsable du patient, incluant le personnel infirmier et aide-soignant, entre autres. La loi Claeys-Leonetti relative à la fin de vie (2016) l’inscrit dans le droit français comme étant obligatoire lors de la mise en place d’une sédation profonde et continue maintenue jusqu’au décès (SPCMD). L’objectif de l’étude est de faire un état des lieux de la connaissance de cet aspect de loi par le personnel soignant d’un institut de cancérologie et d’identifier comment la collégialité se met en place pour une décision de SPCMD selon les services. Nous avons proposé un questionnaire en ligne et anonyme à l’ensemble des acteurs du soin (connaissance de la loi Claeys-Leonetti) puis nous avons rencontré les soignants des différents services en groupes de discussion (cadres, personnel infirmier et aides-soignants) ou en entretiens individuels (médecins). Les résultats montrent que la loi est mieux connue, toutes professions confondues, des jeunes soignants (moins de 5 ans d’expérience) et surtout mieux revendiquée par les infirmières et aides-soignantes que par les médecins. Nous rapportons la diversité de la mise en œuvre de la collégialité pour une décision de sédation, en termes de formalisation, de standardisation et d’interprofessionnalisation. Nous concluons que la mise en place de la collégialité de façon anticipée pour une décision élargit les modes de communication pluri/inter professionnelle et permet d’apaiser la souffrance des patients, des médecins et des soignants.

Health data collected in cohort studies are valuable sources for knowledge generation and the advance of biomedical research. However, the use of these data for research projects beyond the initial purpose raises several ethical, legal, and societal questions regarding the sensitivity of genomic data sourced from vulnerable and ethnic groups, such as African genetic data and material. Federated data infrastructures have become a key approach to make population-scale genomic and biomolecular data accessible across international borders. While the FAIR principles have become a guiding technical resource for data sharing, legal and socio-ethical considerations are equally important for a fair data ecosystem for further uses of genomic data. The Horizon 2020 project CINECA aims to provide a federated cloud-based infrastructure for the discovery, access, and analysis of human genetic and phenotypic data, based on a virtual cohort of 1.4 million individuals from 10 cohorts in Europe, Canada, and Africa. Beside technical solutions, CINECA addresses and provides valuable experience and input on essential ethical, legal, and societal implications and requirements for transnational health data access, sharing and secondary processing for research purposes.

Health data collected in cohort studies are valuable sources for knowledge generation and the advance of biomedical research. However, the use of these data for research projects beyond the initial purpose raises several ethical, legal, technical, and societal questions. This deliverable addresses these challenges regarding reuse of health/genomic data in CINECA from the ethical, legal, and societal issues (ELSI) perspective and in the light of Open Science and FAIR principles. In responding to the requirements for an appropriate IT and governance framework for CINECA and beyond, the research presented in this document builds on a review of GDPR provisions and their institutional sources of interpretation as well as national laws, the corresponding legal, ethical, and social science literature, as well as stakeholder engagement workshops with patient representatives, African researchers, and co-creative exercises with CINECA technical experts. The core of this deliverable are the ethical and legal recommendations that take societal implications into account for data access to European, Canadian, and African cohorts. The recommendations address four key areas: (1) Engagement and benefit sharing as prerequisites for data sharing, (2) Informed consent and reuse of data, (3) Safeguards and respect for privacy, and (4) Further uses and data-access. The deliverable concludes with an outlook on relevant projects such as the European Health Data Space (EHDS) and upcoming ELSI developments regarding data reuse and artificial intelligence (AI).

Health data collected in cohort studies are valuable sources for knowledge generation and the advance of biomedical research. However, the use of these data for research projects beyond the initial purpose raises several ethical, legal, technical, and societal questions. This deliverable addresses these challenges regarding reuse of health/genomic data in CINECA from the ethical, legal, and societal issues (ELSI) perspective and in the light of Open Science and FAIR principles. In responding to the requirements for an appropriate IT and governance framework for CINECA and beyond, the research presented in this document builds on a review of GDPR provisions and their institutional sources of interpretation as well as national laws, the corresponding legal, ethical, and social science literature, as well as stakeholder engagement workshops with patient representatives, African researchers, and co-creative exercises with CINECA technical experts. The core of this deliverable are the ethical and legal recommendations that take societal implications into account for data access to European, Canadian, and African cohorts. The recommendations address four key areas: (1) Engagement and benefit sharing as prerequisites for data sharing, (2) Informed consent and reuse of data, (3) Safeguards and respect for privacy, and (4) Further uses and data-access. The deliverable concludes with an outlook on relevant projects such as the European Health Data Space (EHDS) and upcoming ELSI developments regarding data reuse and artificial intelligence (AI).

Resume L’action medicale humanitaire, au sens large, englobant les missions d’entraide globale entre medecins ORL, est effective depuis de nombreuses annees. Ces missions, qui reposent sur la volonte propre des participants, n’ont pas ete encadrees par des regles specifiques, sur le plan medical, social, ni ethique. Le temoignage de medecins de certains pays « receveurs » de missions, notamment lors du dernier congres de l’IFOS (International Federation of Otorhinolaryngological Societies), en 2017 a Paris, a mis en exergue l’importance de la bonne coordination des missions entre les equipes fournissant de l’aide et les equipes receveuses. Plusieurs reflexions ethiques ont ete publiees sur le sujet, mais peu concernent les missions d’entraide humanitaire en ORL. Nous presentons une mise au point sur ce sujet, a partir de reflexions menees au sein de la SFORL (Societe francaise d’oto-rhino-laryngologie et de chirurgie de la face et du cou) et de l’IFOS, de l’experience de nombreuses missions et d’une revue de la litterature. Une charte specifique de missions d’entraide medicale et humanitaire en ORL a ete elaboree. Cette mise au point est essentielle pour ameliorer la diffusion des connaissances et la formation en ORL a travers le monde en respectant les regles ethiques et socioculturelles indispensables.

Humanitarian action, in the broad sense, including global outreach missions by ENT physicians, has been effective for many years. These volunteer missions have not had any specific regulatory framework, be it medical, social or above all ethical. The testimony of ENT physicians in certain "recipient" countries, in particular during the 2017 Paris Congress of the International Federation of Otorhinolaryngological Societies (IFOS), revealed the importance of adequate coordination between "provider" and "recipient" teams. Several ethical reports have been made, but few specifically focused on ENT outreach. The present review is based on feedback from several missions given to the French Society of OtoRhinoLaryngology and Head and Neck Surgery (SFORL) and IFOS, and on a review of the literature. A specific charter of global outreach and humanitarian missions in ENT has been drawn up. This review is essential for optimizing the sharing of knowledge and training in otorhinolaryngology across the world while respecting mandatory sociocultural and ethical rules.

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.

Genome editing techniques have generated a growing interest following the discovery of the so-called CRISPR-Cas technique. It has raised a global uproar as regards its use in humans, especially after the 2018 announcement of a Chinese scientist who had successfully used CRISPR to edit the genes of twin embryos. Indeed, one of the greatest concerns, although not the only one, has been the use of genome editing technologies to modify the human germline. In such scientific and technological context, the law plays a key role in framing what should be allowed or prohibited, and under which conditions, to find a balance between safe and accessible innovative treatments and respect of fundamental rights in accordance with the societal values and choices. Within the European Union, several institutions have considered the issues raised by human genome editing and several legal texts participate in the establishment of the European regulatory framework applicable to human genome editing. Yet we argue in this paper that the established regulatory landscape is fragmented in the sense of being divided, split or segmented. Such fragmentation, which may have been inevitable for historical and technico-legal reasons, produces effects regarding the role of the current regulatory frameworks applicable to human genome editing. Focusing on the European Union and on the French levels of governance, we discuss how such fragmentation takes place through the identification of determinants of the human genome editing fragmented regulatory landscape. We argue that it should be seen as a process providing more contingent responses to human genome editing reflecting changing political and legal contexts.

Aim To describe the methods and feasibility of the nutritional intervention carried out within the SPRINTT Randomized cotrolled trial. We also illustrate how nutrition interventionists identified participants at risk of malnutrition and the lessons learnt from the nutrition intervention. Findings SPRINTT nutrition intervention was well-received by the majority of the participants. It was mainly carried out using tailored nutrition counselling, but also other means of delivering the intervention were successfully used. Compared with a standard nutrition prescription, an individualized protocol to diagnose malnutrition and follow-up by tailored nutrition counselling helped achieve nutritional targets more effectively in spite of diversity of population in nutritional habits and in some cases reluctance to accept changes. Message The SPRINTT nutrition intervention was feasible and allowed flexibility to the varying needs and cultural differences of this heterogeneous population of frail, older Europeans. It may serve as a model to educate and improve nutrition among community-dwelling older people at risk of mobility limitations. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-020-00438-4., Background The “Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies” (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. Methods SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3–9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0–1.2 g/kg body weight, energy intake of 25–30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. Results Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. Conclusion The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations. Supplementary Information The online version contains supplementary material available at 10.1007/s41999-020-00438-4.

Le séquençage du génome humain est de plus en plus utilisé en oncologie pédiatrique afin de diagnostiquer, de sélectionner un traitement ciblé ou un suivi adapté ou d’identifier une transmission héréditaire. Les investigations génétiques soulèvent des enjeux éthiques et juridiques qui se cristallisent autour du consentement des enfants, mais aussi de leurs parents. Il s’agirait notamment de s’assurer que la décision est prise en connaissance de cause, c’est-à-dire en ayant compris les résultats attendus et les incidences pour soi-même et pour ses proches. Dresser un état des lieux du contexte légal et interroger les enfants et leurs parents permet de préciser dans quelle mesure et dans quelles conditions la parole de l’enfant devrait et pourrait être recherchée et entendue lorsqu’un test génétique est envisagé. Human genome sequencing is increasingly used in pediatric oncology to diagnose, to select targeted treatment or appropriate follow-up, or to identify hereditary transmission. Genetic investigations raise ethical and legal issues, and crystallize around the consent of the individuals concerned, in this case children but also their parents. For any consent, it is necessary in particular to ensure that the decision be taken in full knowledge of the facts, i.e. having understood the expected results or not and the implications for oneself and one’s relatives. Drawing up an inventory of the legal context and interviewing children and their parents make it possible to specify to what extent and under what conditions the child’s voice should and could be sought and heard when a genetic test is envisaged.

BioLaw Journal - Rivista di BioDiritto, N. 1S (2021): Special Issue 1/2021

International audience

This chapter seeks to provide an insight into how the regulatory discretion the GDPR has left to the Member States has been used. It reviews the biobank regulatory environment; whether and how derogations under Article 89(2) GDPR are enabled; the legal basis for scientifc research and role of consent in biobanking post-GDPR; the balance between individual rights and public interest in national law; and fnally, the GDPR’s impact and future possibilities for biobanking. While in exercising their national self-determination the Member States have some possibility to tailor data protection requirements corresponding to their values and aspirations, it risks coming with implications, jeopardizing collaborative research. At this point, it could be argued that Research Ethics Committees (RECs) may have a considerable role to play in navigating the gap between the legal and ethical requirements in both a national as well as a cross-border context.

Since 1978 and the initial French data protection law (Loi n°78-17 du 6 Janvier 1978), consecutive modifications regarding the protection of personal health data, especially in 2004, 2016 and 2018, set up a strict legal regime for processing sensitive personal data, including for research purposes. In recent years, French law has evolved proactively and in parallel with the work of the European Union (EU) on the preparation of what became the General Data Protection Regulation (GDPR), which has been in force since May 2018. This Chapter performs a state-of-art analysis (as of 1 July 2019) of the French legal framework for research biobanks and data protection rules applying to biobanking, in particular those related to data subjects’ rights and Article 89 of the GDPR. Firstly, it provides updated information about the national landscape of active research biobanks in France (Sect. 1). Secondly, it explores how the French law embodies the developments brought by the GDPR and how it envisages individuals’ rights in the context of research biobanking (Sects. 2 and 3). Thirdly, this Chapter analyses existing and potential national exemptions to individuals’ rights, including with regard to Article 89 GDPR, and how France conceives of processing activities of ‘public interest’ (Sect. 4). Finally, the authors address ongoing debates around bioethics law in France and argue for the creation of a specific Act focused on biobanking as a means of integrating, clarifying and developing not only data protection rules but also other activities related to samples, human or not, in a unique, operational and compact act (Sect. 5).

Technological advances have increased the availability of genomic data in research and the clinic. If, over time, interpretation of the significance of the data changes, or new information becomes available, the question arises as to whether recontacting the patient and/or family is indicated. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with research groups from the UK and the Netherlands, developed recommendations on recontacting which, after public consultation, have been endorsed by ESHG Board. In clinical genetics, recontacting for updating patients with new, clinically significant information related to their diagnosis or previous genetic testing may be justifiable and, where possible, desirable. Consensus about the type of information that should trigger recontacting converges around its clinical and personal utility. The organization of recontacting procedures and policies in current health care systems is challenging. It should be sustainable, commensurate with previously obtained consent, and a shared responsibility between healthcare providers, laboratories, patients, and other stakeholders. Optimal use of the limited clinical resources currently available is needed. Allocation of dedicated resources for recontacting should be considered. Finally, there is a need for more evidence, including economic and utility of information for people, to inform which strategies provide the most cost-effective use of healthcare resources for recontacting., NA

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation., NA

Remaining liberties that GDPR provides to EU Member States, as well as remaining ambiguities on GDPR interpretation, continue to feed debates in the ethical and legal literature. Projects like CINECA, which is seeking to facilitate health data exchanges between cohorts in Europe, Canada and Africa, offer valuable experience and input on essential ethical and legal gaps between countries and cohorts on questions such as the ethical lawful basis for international health data sharing and secondary processing for research purposes. The focus of this deliverable will be on answering, both from a legal and an ethical point of view, two priority questions: How to choose a legal basis for CINECA’s data processing? And how should CINECA apprehend broad consent to further data processing? The goal will be to study how the CINECA project could be efficiently conducted (especially data sharing) while being legally compliant with relevant laws and regulations across all member states, and most of all, being compliant with established ethical guidelines and practices across three continents. To answer these questions we have conducted research which has consisted in reviewing GDPR provisions and their institutional sources of interpretation; the corresponding legal and ethical literature; the National laws relevant for the cohorts involved in CINECA as well as cohorts’ internal governance frameworks and privacy policies when available. We present the arguments surrounding the use of GDPR legal exemptions for data processing for scientific research purposes, why researchers are wary to use it for ethical reasons related to the absence of consent, and the practicalities of the use of broad consent for secondary data processing. We recommend using the research exemption as a lawful basis for secondary data processing; Add broad consent as an appropriate safeguard for data subjects’ rights; Restrict the use of the research exemption to research conducted in the “public interest” as defined by National laws.

Remaining liberties that GDPR provides to EU Member States as well as remaining ambiguities on GDPR interpretation keep feeding the debates in the ethical and legal literature. Projects like CINECA, seeking to facilitate health data exchanges between cohorts in Europe, Canada and Africa, offer valuable experience and input on essential ethical and legal gaps between countries and cohorts on questions such as the choice of theethical lawful basis for international health data sharing and secondary processing for research purposes.

Remaining liberties that GDPR provides to EU Member States as well as remaining ambiguities on GDPR interpretation keep feeding the debates in the ethical and legal literature. Projects like CINECA, seeking to facilitate health data exchanges between cohorts in Europe, Canada and Africa, offer valuable experience and input on essential ethical and legal gaps between countries and cohorts on questions such as the choice of the ethical lawful basis for international health data sharing and secondary processing for research purposes. The focus of this deliverable will be on answering, both from a legal and an ethical point of view, two priority questions: How to choose a legal basis for CINECA’s data processing? And how should CINECA apprehend broad consent to further data processing? The goal will be to study how the CINECA project could be efficiently conducted (especially data sharing) while being legally compliant with relevant laws and regulations and most of all, being compliant with established ethical guidelines and practices across three continents.

International audience

International audience

Resume La genetique et, de facon plus precise, l’analyse des caracteristiques genetiques d’une personne, est un des domaines scientifiques qui evolue le plus rapidement avec les neurosciences en ce debut de XXIe siecle. Les diagnostics genetiques et/ou les analyses de predisposition deviennent de plus en plus courants dans nos hopitaux. Ils apportent une aide precieuse a la fois pour la prescription de therapies dites ciblees (notamment en cancerologie) ou pour la mise en place de procedures therapeutiques visant a prevenir ou du moins retarder l’apparition des premiers signes cliniques d’une pathologie. Toutefois, les analyses des caracteristiques genetiques restent generatrices de croyances et de fantasmes dans le grand public amenant a des demandes societales d’utilisation de ces analyses dans des domaines varies depourvus d’interet therapeutique (embauche, compatibilite dans un couple, amities, choix professionnels). Ces demandes surviennent suite aux annonces dans la presse ecrite ou televisee de « decouvertes » la plupart du temps sans fondement scientifique sur l’identification de genes qui seraient non seulement impliques, mais reellement determinants dans des traits humains (empathie, colere, aptitude aux mathematiques, gout pour les voyages…). Devant l’avancee rapide de la genetique et la perception du public, generalement avec peu de culture scientifique philosophique et juridique, Il est necessaire que des enseignements scolaires, des formations universitaires et des conferences destinees au grand public soient organisees afin de sensibiliser la population francaise aux derives eugeniques et societales de la banalisation des analyses de caracteristiques genetiques.

International audience; Following the spectacular rise of epigenetics since the early 2000s, an increasing number of social scientists have called for it to be recognized as an 'interdiscipline', at the crossroads of the life sciences and the social sciences. The aim of this special issue is to advance our knowledge of epigenetics and to address three main issues: the epistemological, conceptual and empirical transformations induced by epigenetic research, the public dissemination of epigenetic knowledge, and finally the normative and sociopolitical implications of epigenetics.; Suite à l’essor spectaculaire de l’épigénétique depuis le début des années 2000, un nombre croissant de chercheurs en sciences sociales demandent à ce qu’elle soit reconnue comme une ‘interdiscipline’, au carrefour des sciences de la vie et des sciences sociales. Ce numéro spécial a pour but de faire progresser notre connaissance de l’épigénétique et d’aborder trois questions principales : les transformations épistémologiques, conceptuelles et empiriques induites par la recherche épigénétique, la diffusion publique des connaissances épigénétiques, et enfin les implications normatives et sociopolitiques de l’épigénétique.

Objectives Pharmacogenetic panel-based testing represents a new model for precision medicine. A sufficiently powered prospective study assessing the (cost-)effectiveness of a panel-based pharmacogenomics approach to guide pharmacotherapy is lacking. Therefore, the Ubiquitous Pharmacogenomics Consortium initiated the PREemptive Pharmacogenomic testing for prevention of Adverse drug Reactions (PREPARE) study. Here, we provide an overview of considerations made to mitigate multiple methodological challenges that emerged during the design. Methods An evaluation of considerations made when designing the PREPARE study across six domains: study aims and design, primary endpoint definition and collection of adverse drug events, inclusion and exclusion criteria, target population, pharmacogenomics intervention strategy, and statistical analyses. Results Challenges and respective solutions included: (1) defining and operationalizing a composite primary endpoint enabling measurement of the anticipated effect, by including only severe, causal, and drug genotype-associated adverse drug reactions; (2) avoiding overrepresentation of frequently prescribed drugs within the patient sample while maintaining external validity, by capping drugs of enrolment; (3) designing the pharmacogenomics intervention strategy to be applicable across ethnicities and healthcare settings; and (4) designing a statistical analysis plan to avoid dilution of effect by initially excluding patients without a gene–drug interaction in a gatekeeping analysis. Conclusion Our design considerations will enable quantification of the collective clinical utility of a panel of pharmacogenomics-markers within one trial as a proof-of-concept for pharmacogenomics-guided pharmacotherapy across multiple actionable gene–drug interactions. These considerations may prove useful to other investigators aiming to generate evidence for precision medicine.

Sudden cardiac death (SCD) accounts for 10-20% of total mortality, i.e., one in five individuals will eventually die suddenly. Given the substantial genetic component of SCD in younger cases, postmortem genetic testing may be particularly useful in elucidating etiological factors in the cause of death in this subset. The identification of genes responsible for inherited cardiac diseases have led to the organization of cardiogenetic consultations in many countries worldwide. Expert recommendations are available, emphasizing the importance of genetic testing and appropriate information provision of affected individuals, as well as their relatives. However, the context of postmortem genetic testing raises some particular ethical, legal, and practical (including economic or financial) challenges. The Public and Professional Policy Committee of the European Society of Human Genetics (ESHG), together with international experts, developed recommendations on management of SCD after a workshop sponsored by the Brocher Foundation and ESHG in November 2016. These recommendations have been endorsed by the ESHG Board, the European Council of Legal Medicine, the European Society of Cardiology working group on myocardial and pericardial diseases, the ERN GUARD-HEART, and the Association for European Cardiovascular Pathology. They emphasize the importance of increasing the proportion of both medical and medicolegal autopsies and educating the professionals. Multidisciplinary collaboration is of utmost importance. Public funding should be allocated to reach these goals and allow public health evaluation.

It is increasingly common in oncology practice to perform tumour sequencing using large cancer panels. For pathogenic sequence variants in cancer susceptibility genes identified on tumour-only sequencing, it is often unclear whether they are of somatic or constitutional (germline) origin. There is wide-spread disparity regarding both the extent to which systematic ‘germline-focussed analysis’ is carried out upon tumour sequencing data and for which variants follow-up analysis of a germline sample is carried out. Here we present analyses of paired sequencing data from 17 152 cancer samples, in which 1494 pathogenic sequence variants were identified across 65 cancer susceptibility genes. From these analyses, the European Society of Medical Oncology Precision Medicine Working Group Germline Subgroup has generated (i) recommendations regarding germline-focussed analyses of tumour-only sequencing data, (ii) indications for germline follow-up testing and (iii) guidance on patient information-giving and consent.

CRISPR Cas9 technique has questioned worldwide its implementation with regards to the existing ethical and legal frameworks. In France, strong debates have occurred in several arenas from professionals to ethicists and lawyers as well as politicians. If all of them acknowledge the scientific progress brought by the discovery of these “molecular scissors” and their abilities to constitute a new pathway for the treatment of genetic diseases in the future, they all agree on the need for an agenda setting in order to evaluate the capacity of the technique to reach the clinic embedded in an agreed ethical and legal framework. The main argument for using CRISPR (clustered regularly interspaced short palindromic repeat) Cas9 with caution was based on the legal impossibility to modify the genome of a human being to be transmitted to the next generation. Germ line editing can be used in the future for treating somatic diseases (in one single person) or on embryos or gametes. The main difference between the two approaches is constituted by the level of the intervention. In the first approach, the therapy will only be used for one person targeting its own cells which can be legally qualified as a human intervention. In the second case, the rationale is to modify one DNA sequence (and/or to replace it) in germ-line. In that case the modification will be transmitted to future generation. From a legal perspective the emergence of CRISPR Cas9 interrogates its qualification and its legal regime. In order to classify this innovation among the legal categories already adopted in the French legal framework, we must investigate the current legal principles stated in the French laws and then the criteria to be applied to this new kind of gene intervention.

International audience; no abstract

Car-T Cells are autologous or allogeneic lymphocytes cells, genetically engineered to express a transmembrane receptor called ?chimeric? because it consists of the assembly of different parts of molecules. These new techniques using biotechnologies (cellular engineering and genetic modifications) are developing in a complex legal context integrating the rules of the European Union (EU) and national rules, aiming to guarantee a high level of security for products and techniques but also for patients. This framework can be either considered as a guaranty for the use of new molecules in a highly secure environment or as an impediment, on the one hand regarding those who want to develop them because of a great complexity in identifying the adequate procedures and regarding the scientific prerequisites expected by the control agencies, and on the other hand by patients who have to wait many years for these innovations to be made available. The development of these innovative therapies will thus question first, the way care and healthcare system should be organised (including for their accessibility) and second, the legal regime and the bioethical principles to be applied for their implementation in the market.

MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda.

Advances in stem cell biology and immunology raise hopes for new developments in regenerative medicine as well as cell-based immune intervention, with potential applications in many medical disciplines. Emerging from the medical practices of organ, tissue and cell transplantations over several decades, the development of cellular therapies nowadays enter a new era in which the industry may take cell manufacturing activities away from academic facilities, using complex procedures for cell engineering and large-scale production at centralized facilities. Recent changes in regulations push towards this historical transition; however, a pragmatic analysis of met and unmet clinical needs, as well as of specific procedural and organizational aspects that govern human cell procurement and processing suggest that a significant role will remain for academic facilities in the near future. Taking advantage of the large experience in the field of haematopoietic stem cell transplantation, we here review actual and potential consequences of regulatory changes in these medical practices, with a focus on the unique system for quality management that has been established in Europe and the United States of America to address specific risks associated with these therapeutic procedures.

The concept of the developmental origins of health and disease (DOHaD) alters our understanding of what constitutes "health" or "disease" intended as chronic, non-communicable diseases, which develop over the life course in high income and emerging countries. It implies a change in paradigm forming a basis for prevention policies across the globe. It also impacts psychological, social, economic, ethical and legal sciences. In line with the unanticipated underpinning epigenetic mechanisms are also the social issues (including public policies) that could be produced by the knowledge related to DOHaD that opens a wide field of inquiry. The information unveiled by epigenetics coupled with information on lifestyle including during the development phase, is of unforeseen nature, raising issues of different nature. Therefore it requires specific attention and research, and a specific support by a pluridisciplinary reflection since the very beginning of its production, to anticipate the questions that might be raised in the future., Le concept de l’origine développementale de la santé et des maladies (« DOHaD », pour developmental origins of health and disease) modifie notre compréhension de ce qui fait qu’un individu développe, au cours de sa vie, les principales maladies chroniques qui affectent les pays riches ou émergents, ou reste en bonne santé. Il implique une évolution du paradigme sur lequel peuvent s’appuyer les politiques de prévention à l’échelle de la planète, dans le champ majeur de l’épidémiologie et des mécanismes des maladies non transmissibles selon la classification de l’Organisation mondiale de la santé. Ce concept ouvre une vision nouvelle également dans les sciences psychologiques, sociales, économiques, éthiques et juridiques. Ce ne sont pas uniquement les aspects épigénétiques qui sont appréhendés par les sciences humaines et sociales mais également les conséquences sociales produites par le développement des connaissances liées à la DOHaD et notamment les politiques publiques qui pourraient être mises en œuvre. Les informations révélées par l’épigénétique, couplées aux informations sur le style de vie et à celles recueillies durant le développement, sont d’un genre nouveau, proche mais différent des informations génomiques, faisant dès lors apparaître des enjeux de nature différente. Elles méritent, de ce fait, d’être accompagnées par une réflexion pluridisciplinaire dès l’origine de leur production afin d’anticiper les questionnements qui pourraient être soulevés dans le futur.

Direct-to-consumer genetic testing: definition & concerns For half a decade now, various companies have started to advertise and/or sell genetic tests directly to consumers. The most popular advertised tests are those that genotype hundreds of thousands of SNPs across the genome and that provide individuals with information about their genetic predisposition for a variety of common disorders (such as Type 2 diabetes), as well as for metabolic reactions (e.g., to food or drugs) and for certain traits (such as baldness). In addition, carrier status information or ancestry information is also often being provided. Although most of these direct-to-consumer (DTC) companies started to provide genetic tests without the intermediate of a medical doctor or other healthcare professional, some companies have started to include healthcare professionals in the provision and/or follow-up of tests [1]. Making reference to individuals’ fundamental right to access genetic information about themselves [2], to better guarantee control over their own genetic information; and to increased prevention and empowerment [3], companies have defended their services [4]. The activities of DTC genetic testing companies have been challenged for many reasons. Major concerns revolve around the limited predictive value, clinical validity and clinical utility of most DTC genetic tests that are being sold [5–7]. Further concerns include the absence and/or dubious quality of pretest and post-test information provision and genetic counseling [8]. DTC companies also lack individualized medical supervision. Although some companies involve physicians, these may function as a way to ‘formally’ sign-off genetic tests in order to circumvent legal issues. Finally, critical comments have been advanced with regard to the inappropriate

Despite the increasing availability of direct-to-c onsumer (DTC)genetic testing, it is currently unclear how such services are regulated in Europe, due to the lack of EU or national legislation specifically addressing this issue. In this article, we provide an overview of laws that could potentially impact the regulation of DTC genetic testing in 26 European countries, namely Austria, Belgium, Cyprus, the Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, the Netherlands and the United Kingdom. Emphasis is placed on provisions relating to medical supervision, genetic counselling and informed consent. Our results indicate that currently there is a wide spectrum of laws regarding genetic testing in Europe. There are countries (e.g. France and Germany) which essentially ban DTC genetic testing, while in others (e.g. Luxembourg and Poland) DTC genetic testing may only be restricted by general laws, usually regarding health care services and patients' rights. This study has not received any funding, but has benefited from interactions within the COST Action IS1303 'Citizen's Health through public-private Initiatives: Public health, Market and Ethical perspectives', supported by COST (European Cooperation in Science and Technology) (http://www.cost.eu).

Technological developments in gene editing raise high expectations for clinical applications, first of all for somatic gene editing but in theory also for germline gene editing (GLGE). GLGE is currently not allowed in many countries. This makes clinical applications in these countries impossible now, even if GLGE would become safe and effective. What were the arguments behind this legislation, and are they still convincing? If a technique can help to avoid serious genetic disorders, in a safe and effective way, would this be a reason to reconsider earlier standpoints? The European Society of Human Reproduction and Embryology (ESHRE) and the European Society of Human Genetics (ESHG) together developed a Background document and Recommendations to inform and stimulate ongoing societal debates. After consulting its membership and experts, this final version of the Recommendations was endorsed by the Executive Committee and the Board of the respective Societies in May 2017. Taking account of ethical arguments, we argue that both basic and pre-clinical research regarding human GLGE can be justified, with conditions. Furthermore, while clinical GLGE would be totally premature, it might become a responsible intervention in the future, but only after adequate pre-clinical research. Safety of the child and future generations is a major concern. Future discussions must also address priorities among reproductive and potential non-reproductive alternatives, such as PGD and somatic editing, if that would be safe and successful. The prohibition of human germline modification, however, needs renewed discussion among relevant stakeholders, including the general public and legislators.

The bioethics laws since their first adoption in 1994 until the latest proposals, have been widely commented and analyzed, regarding the provisions related to the legal qualification and the legal status of the embryo and of the embryonic stem cells. The legal issues raised by these hesitations imply instability for both researchers and health professionals about what they can and cannot do when it comes to the embryo and its cells. Thus, while the protection of the embryo was the subject of a consensus until the end of the 2000s, it now appears as the object of a political will, from researchers and state agencies, to support this research. The legal frameworks have been modified step by step leading to an administrative police that reconciles freedom of research and ethical issues whose legal enforcement remains weak and uncertain. It will therefore be important to highlight the legal and institutional milestones that led to the acceptance of embryo research and to the liberalization of the legal framework. Some doubts will then be expressed about the benefits of this liberalization notably because cases law on the patentability of inventions resulting from this research are a bit of a threat to encourage development perspectives and because embryonic stem cells could remain marginal because of the economic and scientific contexts.

The use of health data is increasingly seen as a central issue for research and also for care. The generation of these data is an added value for the conduct of large-scale studies, it is even considered as an (r) evolution in the methodology of research or even for personalized medicine. Several factors have influenced the acceleration in the use of health data (advances in genetics, technology and diversification of sources) leading to a re-questioning of the legal principles for the protection of health data in both French law and European law. Indeed, first, the massive production of data (Big Data) in the field of health affects the quantity and the quality of the data which consequently reconfigure the tools of protection of private life and on the informational risk. Second, the use of these data is based on existing fundamental principles while raising new challenges for their governance.

Background Governments, funding bodies, institutions, and publishers have developed a number of strategies to encourage researchers to facilitate access to datasets. The rationale behind this approach is that this will bring a number of benefits and enable advances in healthcare and medicine by allowing the maximum returns from the investment in research, as well as reducing waste and promoting transparency. As this approach gains momentum, these data-sharing practices have implications for many kinds of research as they become standard practice across the world. Main text The governance frameworks that have been developed to support biomedical research are not well equipped to deal with the complexities of international data sharing. This system is nationally based and is dependent upon expert committees for oversight and compliance, which has often led to piece-meal decisionmaking. This system tends to perpetuate inequalities by obscuring the contributions and the important role of different data providers along the data stream, whether they be low- or middle-income country researchers, patients, research participants, groups, or communities. As research and data-sharing activities are largely publicly funded, there is a strong moral argument for including the people who provide the data in decision-making and to develop governance systems for their continued participation. Conclusions We recommend that governance of science becomes more transparent, representative, and responsive to the voices of many constituencies by conducting public consultations about data-sharing addressing issues of access and use; including all data providers in decision-making about the use and sharing of data along the whole of the data stream; and using digital technologies to encourage accessibility, transparency, and accountability. We anticipate that this approach could enhance the legitimacy of the research process, generate insights that may otherwise be overlooked or ignored, and help to bring valuable perspectives into the decision-making around international data sharing.

Tumor banks are at the heart of many expectations, hopes, and objectives, and must consider the often-contradictory interests of the different actors wishing to ensure best use is made of collections of human biological material. These actors include: People who want to know their medical status (patients and their families) but who want to be sure medical practitioners and researchers respect their informed consent when accessing their sample and information stored in tumor banks; People who produce and use medical information (medical practitioners, researchers, professional societies), who question how this information is produced and provided; People who finance research and development, who want optimal use to be made of these resources, or even to make a profit from them; People who supply biological samples and associated data (managers of collections or biological resource centers), who want to maximize the use and development of their resources; People who control biological resources (public control structures, public health decision-makers), for whom assessing the risks associated with using samples is paramount; Civil society, which influences the acceptability of the development of biobanks.

International audience; This article highlights the regulatory challenges of the assessment process of Gene Therapy Medicinal Products. It also addresses the puzzling institutional maze that influences the regulatory path for the marketing of these products as shown through various examples in the European Union and in China.