In this position paper of the International Society of CNS Clinical Trials and Methodology (ISCTM), the Orphan Diseases Working Group examines key ethical considerations specific to rare disease neuroscience clinical trials. We address the challenges of maintaining clinical equipoise in small, often heterogenous populations; the justification and limitations of placebo-controlled designs; the ethical complexities introduced by gene therapies and other biologics, including consent, assent, and participation of vulnerable populations; the imperative for responsible data sharing and transparent communication with patient advocacy organizations; and best practices for compassionate use programs. Drawing on existing regulatory frameworks, published literature, and the collective experience of the working group, we offer recommendations intended to guide sponsors, investigators, regulators, and ethics committees in the ethical design and conduct of these critical trials.
Monday, October 19, 2026
Ethical considerations in the conduct of rare disease neuroscience clinical trials
Olugemo, K., Horrigan, J., Busner, J. et al. Ethical considerations in the conduct of rare disease neuroscience clinical trials. Orphanet J Rare Dis (2026). doi:10.1186/s13023-026-04635-5
