Germline-focussed analysis of tumour-only sequencing: recommendations from the ESMO Precision Medicine Working Group.

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.

The humanitarian and outreach ethics charter in ENT. Ethics at the heart of missions.

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.

Legislation of direct-to-consumer genetic testing in Europe: a fragmented regulatory landscape.

Despite the increasing availability of direct-to-consumer (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.

[Legal aspects of biological sample banks]. / Aspects juridiques des banques d'échantillons biologiques.

In order to frame the research on the human biological products, the French legislator has chosen an option consisting in several laws. This situation represents serious difficulties for the researcher. In the first way he will have to apply various general principles corresponding to the protection of persons since the sampling. To these general principles it has to be add more specific rules related to sampling organisation. The complexicity of this system being the references to be taken by the researcher following the organisation level of the samplings. Consequently legislation has to be adapted at this particular subject: human research.

[Ethical aspects of biological sample banks]. / Aspects éthiques des banques d'échantillons biologiques.

Numerous activities in the domain of epidemiology require the constitution or the use of biological sample banks. Such biobanks raise ethical issues. A number of recommendations are applicable to this field, in France and elsewhere. Major principles applicable to biobanks include the respect of person's autonomy, the respect of human body, the respect of confidentiality. These principles are translated into practices through the following procedures: relevant information to the persons regarding their sample management prior to informed consent, opinion of an independent ethics committee, actual implementation of conditions for protecting samples and data. However, although those principles may appear quite simple and obvious, in the context of a largely international practice of research and given the large variety of biobanks, it is not always obvious for researchers to find their way. The attitudes vary between countries, there are numerous texts for various types of biobanks, the same texts raise different interpretations in different institutions, there are new ethical opinions expressed, and mainly the novelty of questions raised by the uses of samples that are possible today, especially in genetics, and were not foreseeable at the time of sampling make the field difficult in practice. This article reviews the types of biobanks, the relevant ethical issues. It also underlines the still unclear or ambiguous situations using some examples of practical situations.

[Ethical and legal aspects of biological sample banks: synthesis, practical questions and proposals]. / Aspects éthiques et réglementaires des collections d'échantillons biologiques: synthèse, questions pratiques et propositions.

The overview of the numerous ethical questions and complex legal framework regarding biological sample collections leads to present in this synthesis 1) tables of the principal ethical recommendations and French or supranational reglementary texts in this domain, with their internet access; 2) to detail the procedures to follow in some practical situations; 3) to underline the still open questions and current debates, as the ethical and legal framework of human biobanks is in deep evolution.

Trends in ethical and legal frameworks for the use of human biobanks.

Numerous studies of genetic epidemiology and post-genomics in respiratory diseases rely on the use of biobanks, defined as organised biological sample collections with associated personal and clinical data. The use of biobanks is increasing and raises several ethical issues. What are the ethical trends and legal frameworks in the post-genomic era? Are there new issues in relation to the developments of techniques and new study designs? How does this affect the clinician's attitudes and relationship with the patients? The main ethical issues encountered are: informed consent; confidentiality; secondary use of samples and data over time; return of results; and data sharing. Different levels and modalities of dealing with such issues are identified and vary from legally binding measures to "soft" regulations, such as ethical recommendations by various committees or professional organisations. A further level of complexity appears with the increasing international dimension of such activities in a context in which national positions vary on those topics. There is a tension between a necessary level of diversity in ethical positions and an indispensable common pedestal of principles and procedures to manage these issues in order to foster research. Current legal and ethical trends favour the facilitation of secondary use of samples, more biobank openness, balanced with a growing attention to dialogue and public/stakeholder consultation, an increased role for research ethics committees and more sophisticated data protection and governance structures.