Objective: The Shannon model is often used to define an expected boundary between non-damaging and damaging modes of electrical neurostimulation. Numerous preclinical studies have been performed by manufacturers of neuromodulation devices using different animal models and a broad range of stimulation parameters while developing devices for clinical use. These studies are mostly absent from peer-reviewed literature, which may lead to this information being overlooked by the scientific community. We aimed to locate summaries of these studies accessible via public regulatory databases and to add them to a body of knowledge available to a broad scientific community. Methods: We employed web search terms describing device type, intended use, neural target, therapeutic application, company name, and submission number to identify summaries for premarket approval (PMA) devices and 510(k) devices. We filtered these records to a subset of entries that have sufficient technical information relevant to safety of neurostimulation. Results: We identified 13 product codes for 8 types of neuromodulation devices. These led us to devices that have 22 PMAs and 154 510(k)s and six transcripts of public panel meetings. We found one PMA for a brain, peripheral nerve, and spinal cord stimulator and five 510(k) spinal cord stimulators with enough information to plot in Shannon coordinates of charge and charge density per phase. Conclusions: Analysis of relevant entries from public regulatory databases reveals use of pig, sheep, monkey, dog, and goat animal models with deep brain, peripheral nerve, muscle and spinal cord electrode placement with a variety of stimulation durations (hours to years); frequencies (10–10,000 Hz) and magnitudes (Shannon k from below zero to 4.47). Data from located entries indicate that a feline cortical model that employs acute stimulation might have limitations for assessing tissue damage in diverse anatomical locations, particularly for peripheral nerve and spinal cord simulation.
Bibliographical noteFunding Information:
Address Correspondence to: Pavel A. Takmakov, Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, White Oak Federal Research Center, Silver Spring, MD, USA. Email: Pavel.Takmakov@fda.hhs.gov * Division of Biology, Chemistry and Materials Science, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, White Oak Federal Research Center, Silver Spring, MD, USA; † Medical Device Innovation Consortium, Minneapolis, MN, USA; ‡ Neuromodulation Division, Boston Scientific Corporation, Valencia, CA, USA; § Department of Neurology, Medical School, University of Minnesota, Minneapolis, MN, USA; ¶ Department of Research & Technology, Advanced Bionics LLC, Valencia, CA, USA; ** Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA; †† Medtronic Plc, Minneapolis, MN, USA; ‡‡ Implantable Electronic Systems Division, St. Jude Medical, Plano, TX, USA; §§ Weldon School of Biomedical Engineering, Birck Nanotechnology Center, Purdue University, West Lafayette, IN, USA; and ¶¶ Division of Biomedical Physics, Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, U.S. Food and Drug Administration, White Oak Federal Research Center, Silver Spring, MD, USA For more information on author guidelines, an explanation of our peer review process, and conflict of interest informed consent policies, please go to http://www.wiley. com/WileyCDA/Section/id-301854.html
This work was sponsored by Medical Device Innovation Consortium (MDIC), a 501(c)3, public-private partnership created to advance regulatory science for patient benefit. The authors would like to thank Dr. Joel Myklebust and Dr. Yunyan Wang (Office of Science and Engineering Laboratories, Center for Devices and Radiological Health, US Food and Drug Administration) for assistance with the manuscript.
- Shannon model
- electrical stimulation
- neural implants
- safety of electrical stimulation