G006 Predicting age of onset and progression of disease in late-onset neurodegenerative genetic diseases: an ethics review and research agenda

<h3>Background</h3> Prognostic biomarker-based models are currently being developed to predict the onset and progression of Huntington’s Disease and Spinocerebellar Ataxia types 1&amp;3. These predictions are invaluable in clinical trials for studying the effectiveness and optimal timing of potential treatments and may offer significant personal utility to mutation carriers. However, the development of these models also raises important ethical questions. <h3>Aims</h3> This study aims to identify the ethical issues raised by these prognostic models and to formulate a research agenda that ensures a responsible implementation. <h3>Methods</h3> We conducted an ethical literature review on presymptomatic genetic testing for HD and a critical interpretative review of biomarker testing in other late-onset, inactionable neurodegenerative diseases. Based on these reviews, we formulated an ethical research agenda for the (near) future. <h3>Results</h3> Key ethical issues include: Benefits and risks: do benefits of biomarker collection outweigh the risks, including potential harms of UF and VUS? Accuracy of such a model: what is a sufficient accuracy level for onset and progression predictions in clinical trials and practice, and who should decide this? Artificial Intelligence: how to avoid biases in data, and should self-learning prediction models be transparent and explainable? Informed consent: should onset and progression predictions be disclosed to research participants, and if so, when and how? <h3>Conclusions</h3> The development of prognostic models involves making decisions with significant ethical implications for their (future) use in research and clinical practice. Anticipating these ethical issues early is crucial for ensuring these models’ justified implementation.