Search

Background: Peripheral Nerve Stimulation (PNS) is an established therapy for chronic neuropathic pain of peripheral origin, typically following nerve injury. However, there is a paucity of Randomized Controlled Trials (RCTs) demonstrating the therapeutic benefits of PNS. The goals of the current study (COMFORT Study) are to document the safety and efficacy of the Nalu Neurostimulation in a PNS RCT, compared to conventional medical management (CMM). Methods/Design: This is a prospective, multicenter, RCT evaluating the treatment of neuropathic pain with PNS therapy. One of the following four regions will be targeted for treatment: low back, shoulder, knee or foot/ankle. Consented subjects will undergo a baseline evaluation, after which they are randomized 2:1 (PNS+CMM arm to CMM arm). Subjects randomized to PNS+CMM arm will undergo a trial implant period using best clinical practices. Subjects who pass the trial phase, by showing a ≥ 50% reduction in pain relative to baseline, will receive the permanent implant. All subjects receiving a permanent implant will be followed for a total of 36 months. At the 3-month primary end point, subjects in CMM arm will be given the option to crossover into PNS+CMM arm, beginning with a trial implant. The study duration is expected to be 5.5 years from first enrollment to last follow-up of last subject and subsequent study closure. Adverse events will be captured throughout the study. Discussion: The COMFORT study, described here, has the potential to demonstrate the efficacy and safety of the Nalu Neurostimulation System in the treatment of peripheral neuropathy. Results of this study will be the first Level-I evidence, out to 36 months, validating the use of this PNS system in the treatment of chronic pain. This study is designed to enroll the largest cohort, to date, of subjects comparing PNS+CMM vs CMM alone. Plain Language Summary: Peripheral nerve stimulation (PNS) has been used for decades to treat neuropathic pain of peripheral origin. This therapy typically involves the placement small (~1 mm diameter) cylindrical electrodes (leads) near the nerve(s) in question, which is then followed by the delivery mild electrical pulses to the target, thereby blocking the pain signal from reaching the central nervous system. Despite the clinical success of this approach, there are few randomized controlled trials (RCTs) demonstrating PNS efficacy in the treatment of peripheral neuralgia/neuropathy. This may be, in large part, due to a paucity of PNS devices that are small enough to deliver this therapy at multiple locations in the extremities and the torso. For example, most implantable pulse generators (IPGs) range in size from 14 to 40 cm3 in volume. The purpose of this RCT is to demonstrate the safety and efficacy of an externally powered micro-IPG (< 1.5 cm3 in volume), in the delivery of PNS to treat peripheral neuropathic pain. Active Arm subjects will receive therapy with the micro-IPG and continue to use conventional medical management (CMM); Control Arm subjects will be treated with CMM only. The primary endpoint is the responder rate at 3-months, in both arms, defined as the percentage of subjects with ≥ 50% pain reduction from baseline following implantation of the micro-IPG. Control Arm subjects will be given the option to crossover to the Active Arm at 3-months. Study subjects in both arms are followed out to 36 months. [ABSTRACT FROM AUTHOR]

Many decisions must be made before relevant uncertainties are revealed; hence robustness approaches to decision making are often considered. There are two major approaches to robustness in the literature: (i) maximizing the value of the worst outcome and (ii) minimizing the maximum ex post regret of the decision. While the first approach seeks the best worst‐case outcome, it may result in substantial opportunity losses relative to the ex post optimal decision; this is particularly critical in new product design decisions as it leaves the leading firm exposed to a late entrant who designs its products after uncertainties are resolved. The second approach seeks to minimize these ex post opportunity losses, but it may expose the decision maker to greater downside risk, that is, lower outcome in the worst case. Most studies have examined one of these approaches in isolation; in contrast, in this study, we explore the trade‐offs between protecting upside regret and downside risk with a focus on a product line design (PLD) problem, which relies greatly on conjoint analysis data. The PLD problem may suffer from significant uncertainty in the partworth utilities which define the attribute‐level consumer preferences on a product for different population segments. Our numerical experiments, based on a real conjoint data set, show that neither robustness approaches dominates the other and hence our proposed approach uses both. We construct a Min‐Value vs. Max‐Relative‐Regret efficient frontier to narrow down the PLD choice and propose a metric to quantify the trade‐offs and finalize the selection. [ABSTRACT FROM AUTHOR]

Background: There is paucity of data from randomized controlled trials supporting the use of peripheral nerve stimulation, a well-established therapy for the treatment of chronic pain. This study was undertaken, in part, to provide randomized controlled trial data in support of patient access to appropriate peripheral nerve stimulation therapy. The COMFORT study is the first large, postmarket, multicenter randomized controlled trials investigating the use of a Food and Drug Administration-cleared micro-implantable pulse generator (IPG) for treating chronic pain via peripheral nerve stimulation therapy., Methods: Consented, eligible subjects were randomized to either the active arm, which received peripheral nerve stimulation and conventional medical management, or the control arm, which received conventional medical management alone and were allowed to cross over to the active arm, after 3 months. Pain and patient-reported outcomes were captured. Therapy responders were subjects who achieved at least a 50% reduction in pain scores compared with baseline. We are reporting the 12-month results of this 36-month study., Results: At 12 months, the responder rate was 87% with a 69% average reduction in pain compared with baseline (7.5±1.2 to 2.3±1.7; p<0.001). Statistical significance was achieved for all patient-reported outcomes. There was an excellent safety profile with no serious adverse device effects or reports of pocket pain. A majority of subjects used unique programming options and found this device easy to use and comfortable to wear., Conclusions: These 12-month results are consistent with previously reported 6-month outcomes from this study, showing durability of peripheral nerve stimulation treatment with the micro-IPG system; subjects realized sustained large reduction in pain and improvement in patient-reported outcomes following treatment with this micro-IPG system., Trial Registration Number: NCT05287373., Competing Interests: Competing interests: GH was a consultant at Nalu Medical, Agitated Solutions, and a co-founder of Nesos. PSS is a consultant for Nalu Medical, Saluda, SPR therapeutics, and Medtronic. He is chief medical officer at electroCore. SK is an employee at Nalu Medical. JM is a consultant at Nalu Medical and owns stock in Nalu Medical. JH is a speaker and consultant for Nalu Medical. MJD consults for Medtronic and Nalu; receives research support from Abbott, Avanos, Averitas, Mainstay, Nalu, Nature Cell, Saol, SPR Therapeutics, Vivex; and owns stock options in HyperVention, SPR Therapeutics, SynerFuse, and Virdio., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: We report the results from the first large, postmarket, multicentre, randomised controlled trial (RCT) evaluating peripheral nerve stimulation (PNS) for the treatment of chronic peripheral pain with a micro-implantable pulse generator (micro-IPG)., Methods: Subjects meeting eligibility were randomised (2:1) to either the active arm receiving PNS and conventional medical management (CMM) or the control arm receiving CMM alone. Treatments were limited to the following areas: lower back, shoulder, knee and foot/ankle., Results: At 6 months, the active arm achieved an 88% responder rate with a 70% average reduction in pain. At the 3-month primary endpoint, the active arm achieved an 84% responder rate with an average pain reduction of 67% compared with the control arm, which achieved a 3% responder rate with an average pain reduction of 6%. Both responder rate and pain reduction in the active arm were significantly better than in the control arm (p<0.001). A majority of patient-reported outcomes also reached statistical significance. There have been no reports of pocket pain and no serious adverse device effects. 81% of subjects found the external wearable component of the PNS system to be comfortable., Conclusions: This study successfully reached its primary endpoint-the active arm achieved a statistically significant superior responder rate as compared with the control arm at 3 months. These RCT results demonstrated that PNS, with this micro-IPG, is efficacious and safe. This ongoing study will follow subjects for 3 years, the results of which will be reported as they become available., Competing Interests: Competing interests: GH is a consultant at Nalu Medical, Agitated Solutions, and a co-founder of Nesos. PS is a consultant for Nalu Medical, Saluda, SPR therapeutics and Medtronic. He is the Chief Medical Officer at electroCore. SK is an employee at Nalu Medical. JM is a consultant at Nalu Medical and owns stock in Nalu Medical. JH is a speaker and consultant for Nalu Medical. MJD consults for Avanos, Nalu, SPR Therapeutics; receives research support from Abbott, Avanos, Averitas, Mainstay, Nalu, Nature Cell, Saol, SPR Therapeutics and Vivex; and owns stock options in SPR Therapeutics, SynerFuse and Virdio., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)