Implicit ethical choices in ultra-rare therapy development: researchers’ perspectives on patient selection and communication, therapy value, and accessibility

BACKGROUND: The development of new highly technological and highly personalized therapies for ultra-rare diseases is one of the fast-advancing areas in biomedicine. Yet such an approach is experimental, resource-intensive, and accessible mostly in affluent countries, thereby provoking ethical concerns. From a constructivist perspective, those therapies are not neutral tools, and ethical concerns are not merely added to science but embedded in the very choices researchers and technology developers make. Early research decisions about how therapy goals are defined, which patients are included, and which diseases are prioritized already include implicit normative decisions that set the further therapy development trajectory. Nonetheless, the perspectives of researchers working on these individualized therapies remain underinvestigated. In this study, we aim to address this gap and explore how researchers developing such therapies understand and enact ethically loaded choices in early therapy development in practice. METHODS: We conducted 15 semi-structured interviews with researchers developing a standardized platform for discovering personalized ASOs for ultra-rare neurodevelopmental disorders. Interviews were subjected to inductive thematic analysis, focusing on semantic themes. We report this study according to the Consolidated Criteria for Reporting Qualitative Research. RESULTS: From the analysis, four main semantic themes were developed inductively. Researchers described patient and disease selection as a matter of feasibility, focusing mainly on the technical aspects of therapy development. They saw emotions as a potential source of bias in the selection process and thus advocate for selection committees and decision-making algorithms that reduce personal involvement. Communication with patients and their families was perceived as an ethically fragile area due to false hope phenomena and the emotional pressure of personal communication. Perceptions of therapy's value varied, ranging from symptom relief and reduced family burden to doubts about whether the intervention was justified given the high translational uncertainty. Finally, researchers identified various barriers to therapy accessibility, yet described them as parts of the landscape rather than as sites for personal actions. CONCLUSIONS: The early stages of individualized therapy development for ultra-rare diseases include implicit ethical choices that are often seen as purely technical. Explicating the ethical component of these choices can help make the process of therapy development more transparent and fair.