Principles of Physiologic Closed-Loop Controllers in Neuromodulation.

RATIONALE: As neurostimulation devices increasingly incorporate closed-loop functionality, the greater design complexity brings additional requirements for risk management and special considerations to optimize benefit. This manuscript creates a common framework on which all current and planned neuromodulation-based physiologic closed-loop controllers (PCLCs) can be mapped, including integration of the "Technical Considerations of Medical Devices with Physiologic Closed-Loop Control Technology" guidance published in 2023 by the United States Food and Drug Administration, a classification of feedback (reactive) and feedforward (predictive) biomarkers, and control systems theory.

RESULTS AND CONCLUSIONS: We explain risk management in the context of this framework and illustrate its applications for three exemplary technologies. This manuscript serves as guidance to the emerging field of PCLCs in neuromodulation, mitigating risk through standardized nomenclature and a systematic outline for rigorous device development, testing, and implementation.