[Suspicion of constitutional abnormality at diagnosis of childhood leukemia: Update of the leukemia committee of the French Society of Childhood Cancers]. / Suspicion d'anomalie constitutionnelle au diagnostic de leucémie chez l'enfant : mise au point du comité leucémies de la Société française des cancers de l'enfant.

The spectrum of childhood leukemia predisposition syndromes has grown significantly over last decades. These predisposition syndromes mainly involve CEBPA, ETV6, GATA2, IKZF1, PAX5, RUNX1, SAMD9/SAMD9L, TP53, RAS-MAPK pathway, DNA mismatch repair system genes, genes associated with Fanconi anemia, and trisomy 21. The clinico-biological features leading to the suspicion of a leukemia predisposition are highly heterogeneous and require varied exploration strategies. The study of the initial characteristics of childhood leukemias includes high-throughput sequencing techniques, which have increased the frequency of situations where a leukemia predisposing syndrome is suspected. Identification of a leukemia predisposition syndrome can have a major impact on the choice of chemotherapy, the indication for hematopoietic stem cell transplantation, and screening for associated malformations and pathologies. The diagnosis of a predisposition syndrome can also lead to the exploration of family members and genetic counseling. Diagnosis and management should be based on dedicated and multidisciplinary care networks.

[Towards more informed consent: Making information understandable]. / Vers un consentement plus éclairé - Rendre l'information accessible.

In clinical research and care, information notices are too often reduced to complicated and hard-to-understand mandatory documents. However, every person has the right to transparent and truthful information. These considerations prompted the creation of a multidisciplinary working group in the fall of 2020, headed by the College des relecteurs de l'Inserm. This group associates the different actors involved in the development, evaluation and use of information notices: Health and research professionals, representatives of patient associations or research foundations, ethicists, jurists, scientific educators and communicators. This group has created a set of texts, pictograms and illustrations, adapted to the people concerned and accepted by all actors. These contents will be easily used by professionals through the app Noticeinfobox©. A pilot phase was conducted to generate the notices of the France Genomic Medicine Plan 2025, used for genetic examinations. This app Noticeinfobox© is a response to society's request to be an actor in its own healthcare and to adopt more ethical and responsible research.

Title: Vers un consentement plus éclairé - Rendre l'information accessible. Abstract: Trop souvent, les notices d'information proposées dans le cadre de recherches cliniques se réduisent à des documents réglementaires difficilement compréhensibles. Pourtant, les personnes concernées doivent avoir accès à une information transparente et loyale. Ces considérations ont motivé la création d'un groupe de travail pluridisciplinaire, piloté par le Collège des relecteurs de l'Inserm, associant les acteurs impliqués dans l'élaboration, l'évaluation et l'utilisation de ces notices d'information. Un ensemble de textes, pictogrammes et illustrations, adaptés aux personnes concernées, validés et facilement utilisables via une application a été créé. Une phase pilote, dans le cadre du plan France médecine génomique 2025, a permis de générer des notices simplifiées pour les examens génétiques. Dans cet article, nous présentons le travail réalisé par le groupe de travail « Notices d'information ¼ afin de répondre à la demande sociétale d'être acteur de son parcours de soin et de contribuer à une recherche plus éthique et responsable.

Study protocol comparing the ethical, psychological and socio-economic impact of personalised breast cancer screening to that of standard screening in the "My Personal Breast Screening" (MyPeBS) randomised clinical trial.

BACKGROUND: The MyPeBS study is an ongoing randomised controlled trial testing whether a risk-stratified breast cancer screening strategy is non-inferior, or eventually superior, to standard age-based screening at reducing incidence of stage 2 or more cancers. This large European Commission-funded initiative aims to include 85,000 women aged 40 to 70 years, without prior breast cancer and not previously identified at high risk in six countries (Belgium, France, Italy, Israel, Spain, UK). A specific work package within MyPeBS examines psychological, socio-economic and ethical aspects of this new screening strategy. It compares women's reported data and outcomes in both trial arms on the following issues: general anxiety, cancer-related worry, understanding of breast cancer screening strategy and information-seeking behaviour, socio-demographic and economic characteristics, quality of life, risk perception, intention to change health-related behaviours, satisfaction with the trial. METHODS: At inclusion, 3-months, 1-year and 4-years, each woman participating in MyPeBS is asked to fill online questionnaires. Descriptive statistics, bivariate analyses, subgroup comparisons and analysis of variations over time will be performed with appropriate tests to assess differences between arms. Multivariate regression models will allow modelling of different patient reported data and outcomes such as comprehension of the information provided, general anxiety or cancer worry, and information seeking behaviour. In addition, a qualitative study (48 semi-structured interviews conducted in France and in the UK with women randomised in the risk-stratified arm), will help further understand participants' acceptability and comprehension of the trial, and their experience of risk assessment. DISCUSSION: Beyond the scientific and medical objectives of this clinical study, it is critical to acknowledge the consequences of such a paradigm shift for women. Indeed, introducing a risk-based screening relying on individual biological differences also implies addressing non-biological differences (e.g. social status or health literacy) from an ethical perspective, to ensure equal access to healthcare. The results of the present study will facilitate making recommendations on implementation at the end of the trial to accompany any potential change in screening strategy. TRIAL REGISTRATION: Study sponsor: UNICANCER. My personalised breast screening (MyPeBS). CLINICALTRIALS: gov (2018) available at: https://clinicaltrials.gov/ct2/show/NCT03672331 Contact: Cécile VISSAC SABATIER, PhD, + 33 (0)1 73 79 77 58 ext + 330,142,114,293, contact@mypebs.eu.

Publisher Correction: Personalized early detection and prevention of breast cancer: ENVISION consensus statement.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Personalized early detection and prevention of breast cancer: ENVISION consensus statement.

The European Collaborative on Personalized Early Detection and Prevention of Breast Cancer (ENVISION) brings together several international research consortia working on different aspects of the personalized early detection and prevention of breast cancer. In a consensus conference held in 2019, the members of this network identified research areas requiring development to enable evidence-based personalized interventions that might improve the benefits and reduce the harms of existing breast cancer screening and prevention programmes. The priority areas identified were: 1) breast cancer subtype-specific risk assessment tools applicable to women of all ancestries; 2) intermediate surrogate markers of response to preventive measures; 3) novel non-surgical preventive measures to reduce the incidence of breast cancer of poor prognosis; and 4) hybrid effectiveness-implementation research combined with modelling studies to evaluate the long-term population outcomes of risk-based early detection strategies. The implementation of such programmes would require health-care systems to be open to learning and adapting, the engagement of a diverse range of stakeholders and tailoring to societal norms and values, while also addressing the ethical and legal issues. In this Consensus Statement, we discuss the current state of breast cancer risk prediction, risk-stratified prevention and early detection strategies, and their implementation. Throughout, we highlight priorities for advancing each of these areas.

Démocratie participative et évolution d'une politique de santé publique ?

This article provides a dual perspective, both academic and operational, on the 2016 scientific and citizen consultation on breast cancer screening and the public health actions being developed. METHOD: In view of controversies around breast cancer screening, the Ministry of Health asked the French National Cancer Institute to organize this consultation to clarify the benefits and limitations of breast cancer screening, health objectives, organizing and tackling the health inequalities of this program. It has combined the setting up of an independent and multidisciplinary steering committee, a conference of citizens and professionals. It relied on the hearing of experts representing the trends of the controversy, on a technical and prospective report and on the analysis of nearly 500 online contributions. At the end of this process, the policy committee produced a report. RESULTS: In the end, two scenarios were presented, leading to a complete overhaul of the current screening process. As a result of this report, the Ministry announced the action plan for the renovation of organized breast cancer screening in 12 measures in April 2017. DISCUSSION: The discussion focuses on the consultation methodology as a tool for health democracy and on the levels of arbitration that led to the action plan. The objective is to reflect on the possible interactions between consultation and decision-making and to propose benchmarks for the development and improvement of this consultation.

Familial disclosure by genetic healthcare professionals: a useful but sparingly used legal provision in France.

Familial disclosure of genetic information is an important, long-standing ethical issue that still gives rise to much debate. In France, recent legislation has created an innovative and unprecedented procedure that allows healthcare professionals (HCPs), under certain conditions, to disclose relevant information to relatives of a person carrying a deleterious genetic mutation. This article will analyse how HCPs in two medical genetics clinics have reacted to these new legal provisions and show how their reticence to inform the patients' relatives on their behalf leads them to use this option sparingly.

[Participatory democracy and development of a public health policy?] / Démocratie participative et évolution d'une politique de santé publique ?

This article provides a dual perspective, both academic and operational, on the 2016 scientific and citizen consultation on breast cancer screening and the public health actions being developed. METHOD: In view of controversies around breast cancer screening, the Ministry of Health asked the French National Cancer Institute to organize this consultation to clarify the benefits and limitations of breast cancer screening, health objectives, organizing and tackling the health inequalities of this program. It has combined the setting up of an independent and multidisciplinary steering committee, a conference of citizens and professionals. It relied on the hearing of experts representing the trends of the controversy, on a technical and prospective report and on the analysis of nearly 500 online contributions. At the end of this process, the policy committee produced a report. RESULTS: In the end, two scenarios were presented, leading to a complete overhaul of the current screening process. As a result of this report, the Ministry announced the action plan for the renovation of organized breast cancer screening in 12 measures in April 2017. DISCUSSION: The discussion focuses on the consultation methodology as a tool for health democracy and on the levels of arbitration that led to the action plan. The objective is to reflect on the possible interactions between consultation and decision-making and to propose benchmarks for the development and improvement of this consultation.

Genetic diseases and information to relatives: practical and ethical issues for professionals after introduction of a legal framework in France.

Health professionals have a role to play in assisting patients to communicate genetic information to their relatives. In France, a specific unique legal framework has been implemented concerning this issue. We questioned professionals about their practice and how it has evolved in this new frame. The French law has opted to lay responsibility for disclosure on the person concerned by a positive test result, without totally excluding some responsibility on the part of the professionals involved, in the information to be disclosed and in the transmission of the information if a patient refuses to do it themselves (indirect disclosure). We designed and validated an online survey to be sent out to healthcare professionals to explore their practice and how they went about implementing the legal provisions. We also sought to determine how healthcare professionals dealt with a patient's refusal to disclose information to their relatives, and whether the legal framework was helpful. We carried out a statistical analysis of the responses to questionnaires to interpret the results by professional category, field of medicine and genetic disorder. The results show that professionals agreed on the relevance of disclosure to relatives. However, they show a range of practices and varying representations of the genetic issue in the framework of disclosure to relatives according to their medical field, their role in the health system and their own interpretations. They indicated a lack of resources, raised some ethical issues and put forward some arguments against contacting relatives themselves.

[Enseignement des sciences et questionnement éthique.] / Enseignement des sciences et questionnement éthique.

Considering the importance of socio-scientific-issues, it has become a necessity to associate teaching sciences and ethics. So, it is relevant to identify tracks which could make this link possible and efficient. This must be done to meet a social expectation which requires that every citizen should be able to take decisions in a complex environment associating scientific knowledge with history, philosophy, economy. The following text relies on conferences and discussions which occured in 2014 on the relation between science education and ethical issues in the secondary school. It's purpose was to present the necessity of this link while giving some practical references and guidelines.

Supporting disclosure of genetic information to family members: professional practice and timelines in cancer genetics.

Disclosure of genetic information within families is one of the longstanding questions under scrutiny in the field of genetics. Most of the probands entrusted with family disclosure succeed in this task, but there are still many problematic cases where it proves difficult. How can professionals help probands disclose this information? What levers can they activate to foster the diffusion of genetic information within families? In the context of a new legal framework concerning this question in France, this paper offers a comprehensive view of the process of genetic counselling in a cancer genetics department. Based on an ethnographic study, it focuses on the interactions between professionals and probands during each step of the testing procedures in order to identify key times when the issue can be addressed. The results show that the question of family disclosure needs to be addressed before, during and after the test. Greater awareness of this continuum among professionals could help them foster family disclosure by supporting the probands at each stage of the testing procedure.

Genetic Test Results and Disclosure to Family Members: Qualitative Interviews of Healthcare Professionals' Perceptions of Ethical and Professional Issues in France.

The benefit of disclosing test results to next of kin is to improve prognosis and-in some cases-even prevent death though earlier monitoring or preventive therapies. Research on this subject has explored the question of intra-familial communication from the standpoint of patients and relatives but rarely, from the standpoint of healthcare professionals. The purpose of this study was to interview relevant healthcare professionals in France, where legislation framing the issue was recently passed. A qualitative study consisting of semi-structured interviews was set up to get a clearer picture of the challenges arising from this issue, its consequences in terms of medical care-service practices, and the positions that frontline professionals have taken in response to this new legal framework. The findings from eight interviews with 7 clinical geneticists and 1 genetic counselor highlight very different patterns of practices among care services and among the genetic diseases involved. It is equally crucial to investigate other issues such as the nature of genetic testing and its consequences in terms of disclosing results to kin, the question of the role of genetic counseling in the disclosure process, the question of prescription by non-geneticist clinicians, and practical questions linked to information content, consent and medical follow-up for patients and their relatives.

Women's participation in breast cancer screening in France--an ethical approach.

BACKGROUND: Breast cancer is a major public health challenge. Organized mammography screening (OS) is considered one way to reduce breast cancer mortality. EU recommendations prone mass deployment of OS, and back in 2004, France introduced a national OS programme for women aged 50-74 years. However, in 2012, participation rate was still just 52.7%, well short of the targeted 70% objective. In an effort to re-address the (in) efficiency of the programme, the French National Cancer Institute has drafted an expert-group review of the ethical issues surrounding breast cancer mammography screening. DISCUSSION: Prompted by emerging debate over the efficiency of the screening scheme and its allied public information provision, we keynote the experts' report based on analysis of epidemiological data and participation rate from the public health authorities. The low coverage of the OS scheme may be partly explained by the fact that a significant number of women undergo mammography outside OS and thus outside OS criteria. These findings call for further thinking on (i) the ethical principles of beneficence and non-malfeasance underpinning this public health initiative, (ii) the reasons behind women's and professionals' behavior, and (iii) the need to analyze how information provision to women and the doctor-patient relationship need to evolve in response to scientific controversy over the risks and benefits of conducting mammographic screening. SUMMARY: This work calls for a reappraisal of the provision of screening programme information. We advocate a move to integrate the points sparking debate over the efficiency of the screening scheme to guarantee full transparency. The perspective is to strengthen the respect for autonomy allowing women to make an informed choice in their decision on whether or not to participate.

[Maternity for others: from desiring a child to desiring a child at any price]. / Maternité pour autrui : du désir d'enfant à l'enfant à tout prix.

Surrogacy is prohibited by French law. On December 17th 2008 the French Court of Cassation has refused the transcription on the French register of civil status of U.S. birth certificates of children born to a surrogate mother in California. Some have been requesting that legislators amend current laws so as to legalize the practice. Such a claim is far from unanimous. Two successive reports of the French Parliament have underlined their opposition to such modifications: the first report has been delivered by a working group of the Senate and the second by the Parliamentary Office for Scientific and Technological Choices. We propose to analyze the elements that are opposed to the legalization of the practice. We do not underestimate the suffering of couples without children or the love they want to give but if surrogacy is forbidden it is because of the numerous difficulties it entails and that can not be bypassed by sentimental considerations.

Evaluation of biobank constitution and use: multicentre analysis in France and propositions for formalising the activities of research ethics committees.

Biobanks are collections of biological material and related files gathered and stored for clinical or research purposes. Here, we investigated the questions raised during the evaluation of biobanks by biomedical Research Ethics Committees (RECs), particularly in the context of genetic research. We sent a questionnaire to all RECs in France to survey their concerns and the ethical criteria used when evaluating research involving the storage of biological samples. Most of the RECs think that they should be consulted to evaluate the constitution of biobanks. The proportion of RECs of this opinion depended on whether the biobank is being constituted in the absence of an associated research project (initially created for clinical purposes or for undefined research) (14/28), whether the biobank is being constituted for research use (21/28) or whether an existing research biobank is being re-used (19/28). Views diverged concerning the way ethics principles are applied, showing that REC evaluations of biobanks might be formalised at each of the following steps: constitution, use and re-use. In this paper, we suggest concrete elements that could be integrated into the application of the new French law concerning the protection of the human beings participating in research as well as into international recommendations.

Communication of pharmacogenetic research results to HIV-infected treated patients: standpoints of professionals and patients.

The aim of pharmacogenetic studies is to adapt therapeutic strategies to individual genetic profiles, thus maximising their efficacy and minimising the likelihood of adverse side effects. Since the advent of personalised medicine, the issue of communicating research results to participants has become increasingly important. We addressed this question in the context of HIV infection, as patients and associations are particularly concerned by research and therapeutic advances. We explored the standpoints of both research professionals and participants involved in a pharmacogenetic study conducted in a cohort of HIV-infected patients. The setting of the research protocol was followed over a 2-year period. Participants' standpoints were collected through a questionnaire and interviews were conducted with research professionals. Of 125 participants, 76% wished to receive individual results and 71% wished to receive collective results; 39% did not know when results might be expected. Communication of global research results is a principle that is generally accepted by professionals. Concerning individual feedback, the professionals felt that it was necessary if it could be of direct benefit to the participant, but they expressed doubts for situations with no recognised benefit. Our results highlight the necessity to consider this issue in greater detail. We suggest the need to anticipate the debates concerning individual feedback, to differentiate between situations and the importance of further investigations on the opportunities and modalities of communication. Finally, our work emphasised the opposite pressures between the pursuit of scientific knowledge and the therapeutic orientation of clinical trials.

Study of the involvement of research ethics committees in the constitution and use of biobanks in France.

Concerns are emerging about the protection of individuals who take part in genetic research involving biobanks. We used several items of a questionnaire sent to 48 French research ethics committees (RECs) to investigate the means by which they evaluate the constitution and use of biobanks, and the elements on which conclusions were based. Most RECs felt they should evaluate the constitution of biobanks in protocols, but not all did so in practice. Harmonization of the competence of RECs for evaluating biobanks is required, particularly concerning information, consent, the duration of sample conservation and the communication of research results. Our results, together with those of others, demonstrate the need to develop rules and guidelines based on common ethical approaches, particularly in the European environment.