Polygenic risk scores in healthcare contexts: what's the scope? An interview study of European healthcare providers and researchers' perspectives on ethical challenges.

Abstract

In the last decade, substantial research efforts have started worldwide to foster the clinical translation of Polygenic Risk Scores (PRS). Understanding the views of key relevant groups becomes timely to critically inform the socio-ethical debate, impact future health policy, and support the development of guidelines for best practices in healthcare contexts. We performed 26 in-depth semi-structured interviews to investigate the perspectives of European researchers and healthcare providers from different specialties (clinical genetics, oncology, cardiology, psychiatry) on the ethical and social implications of PRS uses in healthcare contexts. Findings were conceptualized in four main themes: 1) appropriate clinical use, highlights that PRS should be considered complementary tools aimed at informing a clinical intervention, with notions of appropriateness differing according to clinical goals and condition-type; 2) clinical utility: what's the evidence? captures participants' orientations towards the capability of PRS to improve health outcomes compared to standard care, as well as the barriers, limitations, or emerging areas of utility; 3) balancing risk and responsibility: navigating ethical questions in patient care, addresses classical issues in clinical genetics, including communication and counselling, potential patient harms, relevance of PRS information to family members, and the use of PRS in pediatric settings; 4) searching for standards: clinical guidelines, gathers perspectives on the potential format and content of future clinical guidelines, relevant parties, and contexts of applicability. In conclusion, the present study outlines a framework to define the range of responsible uses in healthcare contexts; however, societal and public health considerations, including priority-setting in national healthcare systems, need to follow for a comprehensive, and contextual, evaluation of PRS.