Neuroprosthetics research has entered a stage in which animal models and proof-of-concept studies are translated into clinical applications, often combining implants with artificial intelligence techniques. This new phase raises the question of how clinical trials should be designed to scientifically and ethically address the unique features of neural prostheses. Neural prostheses are complex cyberbiological devices able to acquire and process data; hence, their assessment is not reducible to only third-party safety and efficacy evaluations as in pharmacological research. In addition, assessment of neural prostheses requires a causal understanding of their mechanisms, and scrutiny of their information security and legal liability standards. Some neural prostheses affect not only human behaviour, but also psychological faculties such as consciousness, cognition, and affective states. In this Viewpoint, we argue that the technological novelty of neural prostheses could generate challenges for technology assessment, clinical validation, and research ethics oversight. To this end, we identify a set of methodological and research ethics challenges specific to this medical technology innovation. We provide insights into relevant ethical guidelines and assess whether oversight mechanisms are well equipped to ensure adequate clinical and ethical use. Finally, we outline patient- centred research ethics requirements for clinical trials involving implantable neural prostheses.