Public Regulatory Databases as a Source of Insight for Neuromodulation Devices Stimulation Parameters

Abstract

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.

Keywords: Electrodes; Shannon model; electrical stimulation; neural implants; safety of electrical stimulation.

Conflict of interest statement

Conflict of Interest: Eric M. Hudak is an employee of Advanced Bionics whose products are mentioned in the manuscript. Shawn C. Kelley, Darrel F. Untereker and Alan Shi are employees of Medtronic whose products are mentioned in the manuscript. G. Karl Steinke and Benjamin P. Hahn are employees of Boston Scientific whose products are mentioned in the manuscript. Chris Condit is an employee of St Jude Medical whose products are mentioned in the manuscript. Gregory F. Molnar and Dawn Bardot are employees of Medical Device Innovation Consortium that provided financial support for this study. Doe Kumsa is associated with Medical Device Innovation Consortium that provided financial support for this study. The remaining authors have no relevant financial relationships to report.

© 2017 International Neuromodulation Society.

Figures

Figure 1

Flow chart of methodology used to obtain PMA summaries of safety and effectiveness data and 510(k) summaries that list neurostimulation parameters. The search yielded 22 PMA devices out of which eight contained information about preclinical animal studies addressing tissue damage from neurostimulation. Three SSEDs contained enough information to calculate charge and charge density per phase and commented on a degree of tissue damage due to stimulation. 154 510(k) devices were identified. Out of those, five summaries for spinal cord stimulators had enough parameters to calculate charge and charge density per phase.

Figure 2

Charge and charge density per phase for neuromodulation devices available from public regulatory databases. Charge and charge density information for approved medical devices obtained from public databases plotted along data from McCreery et al. (9,10) for experiments with acute stimulation in feline cortex. Open rectangles symbols correspond to experiments where no tissue damage was observed. Filled black symbols correspond to data points where tissue damage was observed. Medtronic Activa Summary of Safety and Effectiveness Data (SSED) provides details of an acute stimulation study in pigs with deep brain stimulation leads. For stimulation with k-values from 3.18 to 4.47, mechanical damage could not be reliably distinguished from electrical damage (gray filled circles). The EnteroMedics Maestro SSED for peripheral nerve stimulation (PNS) describes a study in pigs where nerve degeneration was observed after neurostimulation with k =0.58, but according to the summary, it originates from mechanical strain (gray filled stars). The SSED for Nevro Corp Senza spinal cord stimulator (SCS) has details for a study in goats with stimulation at k below zero when no signs of damage were observed (gray filled diamonds). Five 510(k) summaries for SCS devices document that Medtronic Xtrel and Mattrix were cleared to operate with k of 3.23 and 2.99; Renew from ANS was cleared for k of 2.65; Freedom SCSs from Stimwave were cleared for k of 2.61 (2014) and 2.51 (2015) (filled blue semitransparent hexagons, diamonds, circles, triangles and inverted triangles, respectively). It is important to stress that SCSs do not operate in Shannon “near-field” scenario. [Color figure can be viewed at wileyonlinelibrary.com]