Genetic Screening-Emerging Issues.

In many countries, some form of genetic screening is offered to all or part of the population, either in the form of well-organized screening programs or in a less formalized way. Screening can be offered at different phases of life, such as preconception, prenatal, neonatal and later in life. Screening should only be offered if the advantages outweigh the disadvantages. Technical innovations in testing and treatment are driving changes in the field of prenatal and neonatal screening, where many jurisdictions have organized population-based screening programs. As a result, a greater number and wider range of conditions are being added to the programs, which can benefit couples' reproductive autonomy (preconception and prenatal screening) and improve early diagnosis to prevent irreversible health damage in children (neonatal screening) and in adults (cancer and cascade screening). While many developments in screening are technology-driven, citizens may also express a demand for innovation in screening, as was the case with non-invasive prenatal testing. Relatively new emerging issues for genetic screening, especially if testing is performed using DNA sequencing, relate to organization, data storage and interpretation, benefit-harm ratio and distributive justice, information provision and follow-up, all connected to acceptability in current healthcare systems.

Dynamics of reproductive genetic technologies: Perspectives of professional stakeholders.

Reproductive and genetic medicine are evolving rapidly, and new technologies are already impacting current practices. This includes technologies that can identify a couples' risk of having a child with a genetic disorder. Responsible implementation of new technologies requires evaluation of safety and ethics. Valuable insights for shaping governance processes are provided by various stakeholders involved, including healthcare professionals. Their willingness to adopt these technologies and guide the necessary systemic changes is required for the successful implementation of these technologies. In this study, twenty-one semi-structured interviews were conducted with professionals from different disciplines in the field of reproductive and genetic healthcare in the Netherlands. Three emerging technologies were discussed: expanded carrier screening (ECS), non-invasive prenatal diagnosis (NIPD) and germline genome editing (GGE). By probing stakeholders' views, we explored how culture, structure and practice in healthcare is being shaped by innovations and changing dynamics in genetic and reproductive medicine. The general consensus was that the implementation of reproductive genetic technologies nationwide is a slow process in Dutch healthcare. A "typical Dutch approach" emerged that is characterized by restrictive legislation, broad support for people living with disabilities, values of an egalitarian society and limited commercialisation. Different scenarios for embedding ECS in future practice were envisioned, while implementation of NIPD in clinical practice was considered obvious. Views on GGE varied among stakeholders. Previous implementation examples in the Netherlands suggest introduction of new technology involves an organized collective learning process, with pilot studies and stepwise implementation. In addition, introducing and scaling up new technologies is complex due to perceived barriers from the legislative framework and the complex relationship between the government and stakeholders in this area. This paper describes how the international trends and advances of technologies are expected to manifest itself in a national setting.

How to Integrate Personalized Medicine into Prevention? Recommendations from the Personalized Prevention of Chronic Diseases (PRECeDI) Consortium.

Medical practitioners are increasingly adopting a personalized medicine (PM) approach involving individually tailored patient care. The Personalized Prevention of Chronic Diseases (PRECeDI) consortium project, funded within the Marie Sklodowska Curie Action (MSCA) Research and Innovation Staff Exchange (RISE) scheme, had fostered collaboration on PM research and training with special emphasis on the prevention of chronic diseases. From 2014 to 2018, the PRECeDI consortium trained 50 staff members on personalized prevention of chronic diseases through training and research. The acquisition of skills from researchers came from dedicated secondments from academic and nonacademic institutions aimed at training on several research topics related to personalized prevention of cancer and cardiovascular and neurodegenerative diseases. In detail, 5 research domains were addressed: (1) identification and validation of biomarkers for the primary prevention of cardiovascular diseases, secondary prevention of Alzheimer disease, and tertiary prevention of head and neck cancer; (2) economic evaluation of genomic applications; (3) ethical-legal and policy issues surrounding PM; (4) sociotechnical analysis of the pros and cons of informing healthy individuals on their genome; and (5) identification of organizational models for the provision of predictive genetic testing. Based on the results of the research carried out by the PRECeDI consortium, in November 2018, a set of recommendations for policy makers, scientists, and industry has been issued, with the main goal to foster the integration of PM approaches in the field of chronic disease prevention.

Value-based genomic screening: exploring genomic screening for chronic diseases using triple value principles.

BACKGROUND: Genomic screening has unique challenges which makes it difficult to easily implement on a wide scale. If the costs, benefits and tradeoffs of investing in genomic screening are not evaluated properly, there is a risk of wasting finite healthcare resources and also causing avoidable harm. MAIN TEXT: If healthcare professionals - including policy makers, payers and providers - wish to incorporate genomic screening into healthcare while minimizing waste, maximizing benefits, and considering results that matter to patients, using the principles of triple value (allocative, technical, and personal value) could help them to evaluate tough decisions and tradeoffs. Allocative value focuses on the optimal distribution of limited healthcare resources to maximize the health benefits to the entire population while also accounting for all the costs of care delivery. Technical value ensures that for any given condition, the right intervention is chosen and delivered in the right way. Various methods (e.g. ACCE, HTA, and Wilson and Jungner screening criteria) exist that can help identify appropriate genomic applications. Personal value incorporates preference based informed decision making to ensure that patients are informed about the benefits and harms of the choices available to them and to ensure they make choices based on their values and preferences. CONCLUSIONS: Using triple value principles can help healthcare professionals make reasoned and tough judgements about benefits and tradeoffs when they are exploring the role genomic screening for chronic diseases could play in improving the health of their patients and populations.

Barriers and Facilitating Factors for Implementation of Genetic Services: A Public Health Perspective.

More than 15 years after the publication of the sequence of the human genome, the resulting changes in health care have been modest. At the same time, some promising examples in genetic services become visible, which contribute to the prevention of chronic disease such as cancer. These are discussed to identify barriers and facilitating factors for the implementation of genetic services. Examples from oncogenetics illustrate a high risk of serious disease where prevention is possible, especially in relatives. Some 5% of breast cancers and colorectal cancers are attributable to an inherited predisposition. These cancers occur at a relatively young age. DNA testing of relatives of affected patients may facilitate primary and secondary prevention. Training of non-genetic health care workers and health technology assessment are needed, as is translational research in terms of bringing genomics to health care practice while monitoring and evaluating. Stratified screening programs could include cascade screening and risk assessment based on family history. New roles and responsibilities will emerge. A clear assessment of the values implied is needed allowing to balance the pros and cons of interventions to further the responsible innovation of genetic services.

Public attitudes towards preventive genomics and personal interest in genetic testing to prevent disease: a survey study.

BACKGROUND: Genetic testing and family history assessment can be used as an aid in the prevention of common chronic diseases. The aim of this study was to determine public attitudes and interests towards offering genetic testing and family history-based risk assessment for common chronic disease prevention. METHODS: Cross-sectional questionnaire survey of a consumer panel representative for the Dutch population. The questionnaire was sent to 1399 panel members, aged ≥ 18 years. RESULTS: The response was 70% (978/1399). About half of the respondents expressed an interest in genetic testing to prevent specific diseases (cancer, cardiovascular disease, diabetes or dementia), with lower-educated respondents showing more interest than higher-educated respondents. Few respondents (24%) agreed that people should be preventively tested for all kinds of diseases. According to the respondents, genetic testing should be performed in the hospital (66%) and be directed to curable (57%) or preventable diseases (69%). Half of the respondents believed that family history assessment could help prevent disease, but only 21% thought it should be offered to everyone, as this could cause people to be worried. A minority (12%) reported that their family history had been assessed, whereas 59% did not have it assessed and did not think this would be necessary. Respondents have differentiated interests in preventive genomics, which varies depending on sex, age and level of education. CONCLUSIONS: Members of the public are interested in genetic testing for preventable and curable diseases, but they are ambivalent about family history risk assessment to prevent disease.

The challenge of implementing genetic tests with clinical utility while avoiding unsound applications.

Genetics and genomics have developed fast in the last decade, but have not revolutionized medicine, as some had expected. While translation of research findings to public health applications is lagging behind, direct-to-consumer (DTC) offers of genetic testing have become available, both for monogenic and severe genetic disorders and for genetic variants possibly associated with common complex diseases (susceptibility variants). The European Society of Human Genetics is concerned about the way in which commercial companies are currently introducing genetic tests into the market outside of the scope of the traditional health-care system. There is a sort of a paradox between the lagging implementation in health care of the few genetic tests with proven clinical utility, on the one hand, and the speedy DTC offer of tests, with or without clinical utility. To translate research findings into appropriate clinical applications, assessment of the clinical validity and utility is needed. Many of the parameters needed in assessment frameworks are not available yet. Clinically relevant associations between genetic variants and disease risks have been established, e.g., in oncogenetics and cardiogenetics, and can be used to reflect on the possibilities and obstacles in using the new genetics in public health. In the absence of sufficient information on clinical validity and clinical utility, introduction of genetic tests in common complex disorders is often premature. Priority should be given to settings where clinical utility is proven or likely, to gain additional information concerning diagnosis, prognosis, and disease management. Monitoring and evaluation are essential.