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INTRODUCTION: The evidence for spinal cord stimulation (SCS) has been criticized for the absence of blinded, parallel randomized controlled trials (RCTs) and limited evaluations of the long-term effects of SCS in RCTs. The aim of this study was to determine whether evoked compound action potential (ECAP)-controlled, closed-loop SCS (CL-SCS) is associated with better outcomes when compared with fixed-output, open-loop SCS (OL-SCS) 36 months following implant. METHODS: The EVOKE study was a multicenter, participant-blinded, investigator-blinded, and outcome assessor-blinded, randomized, controlled, parallel-arm clinical trial that compared ECAP-controlled CL-SCS with fixed-output OL-SCS. Participants with chronic, intractable back and leg pain refractory to conservative therapy were enrolled between January 2017 and February 2018, with follow-up through 36 months. The primary outcome was a reduction of at least 50% in overall back and leg pain. Holistic treatment response, a composite outcome including pain intensity, physical and emotional functioning, sleep, and health-related quality of life, and objective neural activation was also assessed. RESULTS: At 36 months, more CL-SCS than OL-SCS participants reported ≥50% reduction (CL-SCS=77.6%, OL-SCS=49.3%; difference: 28.4%, 95% CI 12.8% to 43.9%, p

INTRODUCTION: Chronic pain patients may experience impairments in multiple health-related domains. The design and interpretation of clinical trials of chronic pain interventions, however, remains primarily focused on treatment effects on pain intensity. This study investigates a novel, multidimensional holistic treatment response to evoked compound action potential-controlled closed-loop versus open-loop spinal cord stimulation as well as the degree of neural activation that produced that treatment response. METHODS: Outcome data for pain intensity, physical function, health-related quality of life, sleep quality and emotional function were derived from individual patient level data from the EVOKE multicenter, participant, investigator, and outcome assessor-blinded, parallel-arm randomized controlled trial with 24 month follow-up. Evaluation of holistic treatment response considered whether the baseline score was worse than normative values and whether minimal clinical important differences were reached in each of the domains that were impaired at baseline. A cumulative responder score was calculated to reflect the total minimal clinical important differences accumulated across all domains. Objective neurophysiological data, including spinal cord activation were measured. RESULTS: Patients were randomized to closed-loop (n=67) or open-loop (n=67). A greater proportion of patients with closed-loop spinal cord stimulation (49.3% vs 26.9%) were holistic responders at 24-month follow-up, with at least one minimal clinical important difference in all impaired domains (absolute risk difference: 22.4%, 95% CI 6.4% to 38.4%, p=0.012). The cumulative responder score was significantly greater for closed-loop patients at all time points and resulted in the achievement of more than three additional minimal clinical important differences at 24-month follow-up (mean difference 3.4, 95% CI 1.3 to 5.5, p=0.002). Neural activation was three times more accurate in closed-loop spinal cord stimulation (p

BACKGROUND: Spinal cord stimulation (SCS) is an established chronic pain treatment, but the effectiveness of traditional, open-loop paradigms has been plagued by variable sustainability in a real-world setting. A new approach, utilizing evoked compound action potential (ECAP) controlled closed-loop (CL) SCS, continuously monitors spinal cord activation and automatically adjusts the stimulation amplitude of every pulse, maintaining stimulation at the prescribed ECAP level through this continual feedback mechanism. Recent studies demonstrated the long-term safety and efficacy of ECAP-controlled CL-SCS. Here, we report the design of a prospective, multicenter, single-arm feasibility study to characterize clinical outcomes in a real-world chronic pain population utilizing ECAP-controlled CL-SCS. Objective neurophysiological measurements such as device performance and patient therapy compliance, will be analyzed against baseline biopsychosocial assessments, to explore the clinical utility of these objective physiologic biomarkers in patient phenotyping. METHODS: This study will enroll up to 300 subjects with chronic, intractable trunk and/or limb pain in up to 25 United States investigation sites. Subjects meeting eligibility criteria will undergo a trial procedure and a permanent implant following a successful trial. Neurophysiological measurements (measured in-clinic and continuously during home use) and clinical outcomes including pain, quality-of-life, psychological, emotional, and functional assessments will be collected at baseline, trial end, and up to 24-months post-implantation. DISCUSSION: Associations between objective neurophysiological data, clinical evaluation and patient-reported outcomes may have important clinical and scientific implications. They may provide novel insights about the chronic pain pathophysiology, its modulation during CL-SCS, and identification of pain phenotypes and/or mechanisms associated with treatment response during SCS trials and long-term therapy. Data from the ECAP study could lead to improvements in diagnosis, assessment, patient identification and management of chronic pain. It could also provide the foundation for development of a new SCS treatment approach customized by the patients pain phenotype, unique neurophysiology, and disease severity.

Introduction: Chronic pain is a personal experience influenced by multiple biopsychosocial factors. Using a pain intensity measure alone to assess the effectiveness of a chronic pain intervention fails to fully evaluate its impact on the multifaceted chronic pain experience. The holistic minimal clinically important difference (MCID) is a composite outcome developed to provide a comprehensive assessment of chronic pain in response to intervention, across 5 outcome domains: pain intensity, health-related quality of life, sleep quality, physical, and emotional function. To focus on domains where the individual need is greatest, the holistic MCID reflects the cumulative MCID averaged over only the domains where subjects were impaired preintervention., Objectives: To assess the internal and construct validity of the Holistic MCID score to inform its future use as an evidence-based tool., Methods: This validation study was undertaken using data from the EVOKE trial with 111 patients up to 24-month follow-up. Internal consistency of the holistic MCID was assessed using Cronbach alpha statistic and dimensional exploration using principal component analysis., Results: The holistic MCID measure demonstrated strong internal consistency with Cronbach alpha >0.7 at all follow-ups. Principal component analysis showed one overarching holistic dimension to be present in the composite. Construct validity was demonstrated by an increase in the holistic MCID score being associated with both increased Patients' Global Impression of Change, EuroQol visual analogue scale score, and each of the outcome domains in a "leave-one-out" analysis (all P < 0.001)., Conclusion: The holistic MCID provides a valid measure for the comprehensive, personalized assessment of response after a chronic pain intervention. The validity of the holistic MCID requires further confirmation in other chronic pain populations and with different interventions., Competing Interests: R.S.T. reports consultancy fees from Medtronic, Nevro and Saluda Medical outside the submitted work. C.M.M. is employed by NAMSA, a company that provides consulting and testing services to medical device manufacturers. N.A.M. reports receiving grants from Neuros, Mesoblast, and Vivex Biologics, as well as consulting as a medical monitor for Saluda Medical, Nevro, Vivex Biologics, Mainstay, Sollis Therapeutics, and Vertos outside the submitted work. J.W.K. is an advisory board member for Boston Scientific, Medtronic, Abbott, and Saluda Medical. J.E.P. reports research and consulting fees from Saluda Medical during the conduct of the study; consultancy for Abbott, Medtronic, Saluda Medical, Flowonix, SpineThera, Vertos, Vertiflex, SPR Therapeutics, Tersera, Aurora, Spark, Ethos, Biotronik, Mainstay, WISE, Boston Scientific, and Thermaquil outside the submitted work; has received grant and research support from: Abbott, Flowonix, Aurora, Painteq, Ethos, Muse, Boston Scientific, SPR Therapeutics, Mainstay, Vertos, AIS, and Thermaquil outside the submitted work; and is a shareholder of Vertos, SPR Therapeutics, Painteq, Aurora, Spark, Celeri Health, Neural Integrative Solutions, Pacific Research Institute, Thermaquil, and Anesthetic Gas Reclamation. C.W.H. has received consultancy fees from Saluda Medical and Genecentrix outside the submitted work. S.J.C. reports receiving grants from Saluda Medical, Vertos, Mainstay, and Vivex outside the submitted work. L.K. reports receiving grants from Nevro, Neuros, Avanos, Medtronic, Neuralace, and Xalud Therapeutics and financial support from Nevro, Avanos, and Saluda Medical outside the submitted work. C.A.G. reports personal fees and other from SPR, and personal fees from Nevro, Nalu, Biotronik, Boston Scientific and Saluda Medical outside the submitted work. E.A.P. has received research support from Mainstay, Medtronic, Neuros Medical, Nevro Corp, ReNeuron, SPR, and Saluda Medical outside the submitted work, as well as personal fees from Abbott Neuromodulation, Biotronik, Medtronic Neuromodulation, Nalu, Neuros Medical, Nevro, Presidio Medical, Saluda Medical, and Vertos outside the submitted work. She holds stock options from SynerFuse and neuro42. K.V.P. is a consultant and speaker for Abbott. S.E. reports consultancy fees from Medtronic, and Mainstay Medical outside the submitted work. He has received department research funding from the National Institute of Health Research, Saluda Medical and Medtronic. R.M.L. is an uncompensated consultant for Biotronik, Abbott, Nalu, Saluda Medical, and Mainstay Medical and has stock options from Nalu and Saluda Medical. C.G. reports payment to his institution (for part of his salary) and stock options received from Mainstay, personal fees from Mainstay, Saluda Medical, Persica, and Iliad outside the submitted work, research funded by Sollis, expert witness testimony fees, and serves as Editor-in-Chief of Pain Practice. S.D. has received consulting payments from Averitas Pharma and Biotronik outside the submitted work. A.A. reports consultancy for Medtronic, Avanos, and StimWave outside the submitted work. P.B. reports consulting fees from Abbott and PainTEQ outside the submitted work. E.H., A.L., N.S. and R.V.D. are employees of Saluda Medical. R.V.D. has previously received consultancy fees from Mainstay Medical, Medtronic, and Saluda Medical. D.J.C. has consulted for AbbVie, Heron Therapeutics, Aptinyx, Neumentum, Regeneron Pharmaceuticals, Swing Therapeutics, Virios Therapeutics, Allergan Sales, Eli Lilly and Company, H. Lundback A/S, Pfizer, Samumed, Tonix Pharmaceuticals. T.J.N. has received consultancy fees from Saluda Medical outside the submitted work. The remaining authors declare no conflict of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The International Association for the Study of Pain.)