La légitimité d'une éventuelle application de la thérapie germinale humaine : les aspects juridiques et éthiques

La thérapie germinale est une avenue médicale qui est loin de pouvoir être appliquée de manière sécuritaire et responsable car les connaissances médicales actuelles sont insuffisantes. De surcroît, l'encadrement normatif qui l'entoure est unanime et clame la non-acceptabilité de son application humaine. Certains instruments adoptent une approche rigide en la prohibant formellement, d'autres adoptent une approche flexible en demeurant ouverts à une éventuelle application. Il y a donc divergence quant à la légitimité de cette technique. La médecine moderne doit reposer sur des principes directeurs issus de diverses sources, empruntées au droit et à l'éthique. Les principes retenus pour examiner la légitimité de la thérapie germinale sont tirés, d'une part, des droits et libertés fondamentales: ce sont les principes fondamentaux de dignité, de liberté, d'égalité. D'autre part, ils sont issus des règles d'éthique de la recherche: plus particulièrement le principe de bienfaisance (nonmalfaisance) et celui du respect de la personne. La perspective d'une éventuelle application humaine de la thérapie germinale ne porte pas nécessairement atteinte aux principes fondamentaux, dépendamment du genre d'application qui est envisagé. Une application restreinte, appliquée dans des circonstances particulières et en vue de soulager ou d'éliminer certaines formes de détresses et de souffrances, pourrait être conforme aux principes qui soutiennent les droits et libertés fondamentales. La thérapie germinale soulève des questions éthiques difficiles et parfois inédites, notamment l'extension des risques aux générations futures et l'obligation d'un suivi à long terme pour des descendants qui n'auront pas eux-mêmes donné leur consentement à cette «thérapie». La thérapie germinale est présentement non acceptable mais ne devrait pas faire l'objet d'une prohibition totale.Germ-line therapy is far from being applied in a secure and responsible way because of insufficient medical knowledge. The unanimity against its human application is manifest in the normative frameworks which universally reject it as unacceptable. Certain instruments adopt a rigid approach and formally prohibit it, while others adopt a flexible approach by remaining open to possible applications. There is significant divergence on the legitimacy of this technique. Modem medicine must rest on guiding principles stemming from various sources borrowed from law and from ethics. Framing principles are derived, on one hand, from fundamental rights and freedoms such as the principles of dignity, liberty, and equality, and on the other hand, from the rules of research ethics based on principles such as beneficence and the respect for persons. The prospect of human applications of germ-line therapy does not inevitably infringe on fundamental principles. It depends the application envisaged. A restricted application, used in specific circumstances to relieve or eliminate certain forms of suffering, could respect the principles endorse fundamental rights and freedoms. Germ-line therapy raises difficult and sometimes new ethical questions: notable examples include the extension of the risks to persons other than the treated subject and the obligation of long-term follow-up for the descendants who did not consent to the research. Germ-line therapy is presently unacceptable given the current state ofknowledge; however, it should not be the object of a total prohibition

Whither Pediatric Research and Predisposition Genetic Testing?

[À l'origine dans / Was originally part of : CRDP - Droit, biotechnologie et rapport au milieu]Research in which children undergo genetic testing for predisposition to adult-onset diseases or disorders can lead to a better understanding of these conditions. It can possibly also help encourage early detection and the development of clinical and preventive interventions for those found to be at increased hereditary risk. Increasingly, predisposition testing is becoming part of pediatric genetic research. However, the paucity of normative texts about the conduct of pediatric research using predisposition genetic testing generates complex legal and ethical issues. Drawing on the current texts that govern predisposition genetic testing in research and the norms of pediatric research, we outline points of consensus and divergence as well as recommendations regarding predisposition genetic testing in pediatric research

La recherche pédiatrique et l’utilisation des tests génétiques de prédisposition : où en sommes-nous ?

[À l'origine dans / Was originally part of : CRDP - Droit, biotechnologie et rapport au milieu]Utiliser des tests génétiques de prédisposition en recherche pédiatrique pourrait aider à parvenir à une meilleure compréhension des maladies ou désordres affectant les adultes. Cela pourrait aussi possiblement aider à la détection précoce et au développement de soins préventifs ou cliniques pour les personnes héréditairement plus à risque. De plus en plus, les tests génétiques de prédisposition deviennent un élément de la recherche génétique pédiatrique. Or, la rareté des textes normatifs encadrant l’utilisation des tests génétiques de prédisposition en recherche pédiatrique soulève plusieurs enjeux éthiques et légaux complexes. Après avoir exposé l’encadrement normatif entourant l’utilisation des tests génétiques de prédisposition en recherche ainsi que celui de la recherche pédiatrique, nous présenterons les éléments de consensus ou de divergence ainsi que nos recommandations ayant trait à l’utilisation des tests génétiques de prédisposition en recherche pédiatrique

Parental Access to Children's Raw Genomic Data in Canada: Legal Rights and Professional Responsibility

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

Legal approaches regarding health-care decisions involving minors: implications for next-generation sequencing

The development of next-generation sequencing (NGS) technologies are revolutionizing medical practice, facilitating more accurate, sophisticated and cost-effective genetic testing. NGS is already being implemented in the clinic assisting diagnosis and management of disorders with a strong heritable component. Although considerable attention has been paid to issues regarding return of incidental or secondary findings, matters of consent are less well explored. This is particularly important for the use of NGS in minors. Recent guidelines addressing genomic testing and screening of children and adolescents have suggested that as ‘young children' lack decision-making capacity, decisions about testing must be conducted by a surrogate, namely their parents. This prompts consideration of the age at which minors can provide lawful consent to health-care interventions, and consequently NGS performed for diagnostic purposes. Here, we describe the existing legal approaches regarding the rights of minors to consent to health-care interventions, including how laws in the 28 Member States of the European Union and in Canada consider competent minors, and then apply this to the context of NGS. There is considerable variation in the rights afforded to minors across countries. Many legal systems determine that minors would be allowed, or may even be required, to make decisions about interventions such as NGS. However, minors are often considered as one single homogeneous population who always require parental consent, rather than recognizing there are different categories of ‘minors' and that capacity to consent or to be involved in discussions and decision-making process is a spectrum rather than a hurdle

Reporting practices for unsolicited and secondary findings from next-generation sequencing technologies: Perspectives of laboratory personnel

While next-generation sequencing (NGS) has enormous potential to identify genetic causes of disease, the nature of the technology means that it can also identify additional information about the individual receiving sequencing that is unrelated to the original rationale for testing. Reporting these unsolicited findings (UF) to clinicians, and subsequently to patients, could lead to potentially lifesaving interventions. Most international guidelines provide limited specific recommendations as to whether these UF should be reported. Little research has been conducted exploring which of these variants are reported in practice. Twenty-six interviews were conducted with 27 laboratory personnel, representing 24 laboratories in Europe (12), Canada (five), and Australasia (Seven) to explore their reporting practices. There is considerable variation between laboratories in the reporting of UF. While some limit their reporting to findings that are relevant to the clinical question, others report UF to varying degrees. In addition, most laboratory personnel interviewed said that their laboratories do not actively search for secondary findings in disease-causing genes unrelated to the clinical question, such as those suggested by the American College of Medical Genetics and Genomics. Our study highlights that laboratories are still grappling with decisions about which UF to report from NGS and are calling for more guidance.status: publishe

Reporting practices for variants of uncertain significance from next generation sequencing technologies

The nature of next generation sequencing technologies (NGS) results in the generation of large amounts of data and the identification of numerous variants, for some of which the clinical significance may be difficult to ascertain based on our current knowledge. These Variants of Uncertain Significance (VUS) may be identified in genes in which the function is known or unknown and which may or may not be related to the original rationale for sequencing the patient. Little is known about whether laboratories report VUS to clinicians and current guidelines issued by some of the most notable professional bodies do not provide specific recommendations on this point. To address this, 26 interviews were conducted with 27 laboratory personnel, representing 24 laboratories in Europe (12), Canada (5) and Australasia (7) in order to explore their reporting practices. Participants highlighted that the classification of variants is a real challenge despite the presence of classification guidelines. We identified variation in the reporting practices of VUS across the laboratories within the study. While some laboratories limit their reporting to variants that are pathogenic and thought to be causative of the phenotype, more commonly laboratories report VUS when they are identified in genes related to the clinical question. Some laboratories will also report VUS in candidate genes. VUS that are secondary findings are generally not reported. While it is unclear whether uniformity in reporting is desirable, exploring the perspectives of laboratory personnel undertaking these analyses are critical to ensure the feasibility of any future reporting recommendations.status: publishe

Reporting practices for next generation sequencing technologies: A qualitative study with laboratory personnel

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Do It Yourself Newborn Screening

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