Patterson, Denis G.

Background The efficacy of EVOKE therapy, a closed-loop spinal cord stimulation (SCS) system, has been demonstrated in a double-blinded randomized controlled trial (RCT). RCT evidence, however, may not be generalizable to clinical practice, while limitations of real-world evidence may affect its validity. The aim of this study was to evaluate the effectiveness of EVOKE therapy in routine clinical practice employing a rigorous data collection approach. Methods The ECAP study was a prospective, multicenter, single-arm, pragmatic study that enrolled SCS candidates with chronic, intractable trunk and/or limb pain in 22 US investigational sites. PROMIS-29 questionnaire and objective neurophysiological metrics were collected, and minimal clinically important differences (MCIDs) were used to characterize baseline dysfunction and response to EVOKE therapy both at trial end and maximal analgesic effect post-implant visit. Pre-specified subgroup analyses were conducted based on diagnosis. Results EVOKE therapy observed included a dose ratio of 1.3 and neural dose accuracy of 2.8 μV. Improvements of >1 MCID were observed for all domains and improvements of ≥2 MCIDs were observed for six of the seven domains. Improvements observed at trial end were maintained or improved at post-implant visit, with statistically significant improvement in holistic MCID (MD 0.2, 95% CI 0.1 to 0.4, p=0.004), and a significantly greater proportion of patients considered holistic MCID responders (p=0.047). Subgroup analysis by diagnosis showed similar outcomes. Conclusions EVOKE therapy was associated with clinically meaningful improvements in a real-world chronic pain population across different subgroups and disease pathologies, with effects observed at trial end reproduced at post-implant visit.

Abstract Background Spinal cord stimulation (SCS) is a highly effective therapy for treatment of chronic pain, however due to the complexity of pain, measuring a subject’s long-term response to the therapy remains difficult. Frequent measurement of patient-reported outcomes (PROs) to reflect multiple aspects of subjects’ pain is a crucial step in determining therapy outcomes. However, collecting full-length PROs is burdensome for both patients and clinicians. The objective of this work is to investigate the feasibility of using limited sets of outcomes from multiple PROs to accurately characterize subjects’ response to SCS therapy. Methods Validated PROs were used to capture pain, physical function and disability, as well as psychometric, satisfaction, and global health metrics. PROs were collected from 509 patients implanted with a neurostimulator enrolled in the post-market REALITY study. Combination of Pearson’s correlation and factor analysis was used to eliminate highly correlated questions and find the minimal meaningful set of questions within the predefined domains of each scale. Results The shortened versions of the questionnaires presented almost identical accuracy for classifying SCS therapy outcome as compared to the validated full-length versions. In addition, principal component analysis was performed on all the PROs and showed a robust clustering of pain intensity, psychological factors, physical function, and sleep across multiple PROs. A selected set of questions captured from multiple PROs can provide adequate information for measuring SCS therapy outcomes. Conclusions These shorter and more targeted PROs could result in better patient engagement, enhanced and more frequent data collection processes for digital health platforms, and ultimately increased patient satisfaction with SCS therapy. Trial registration Data for our analysis were extracted from the ongoing prospective, multicenter, international REALITY (Long-Term Real-World Outcomes Study on Patients Implanted with a Neurostimulator) study (NCT03876054).