Durable multimodal and holistic response for physiologic closed-loop spinal cord stimulation supported by objective evidence from the EVOKE double-blind randomized controlled trial.

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<0.001 at all time points). CONCLUSION: The results of this study suggest that closed-loop spinal cord stimulation can provide sustained clinically meaningful improvements in multiple domains and provide holistic improvement in the long-term for patients with chronic refractory pain. TRIAL REGISTRATION NUMBER: NCT02924129.

ECAP-controlled closed-loop versus open-loop SCS for the treatment of chronic pain: 36-month results of the EVOKE blinded randomized clinical trial.

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<0.001) and ≥80% reduction (CL-SCS=49.3%, OL-SCS=31.3%; difference: 17.9, 95% CI 1.6% to 34.2%, p=0.032) in overall back and leg pain intensity. Clinically meaningful improvements from baseline were observed at 36 months in both CL-SCS and OL-SCS groups in all other patient-reported outcomes with greater levels of improvement with CL-SCS. A greater proportion of patients with CL-SCS were holistic treatment responders at 36-month follow-up (44.8% vs 28.4%), with a greater cumulative responder score for CL-SCS patients. Greater neural activation and accuracy were observed with CL-SCS. There were no differences between CL-SCS and OL-SCS groups in adverse events. No explants due to loss of efficacy were observed in the CL-SCS group. CONCLUSION: This long-term evaluation with objective measurement of SCS therapy demonstrated that ECAP-controlled CL-SCS resulted in sustained, durable pain relief and superior holistic treatment response through 36 months. Greater neural activation and increased accuracy of therapy delivery were observed with ECAP-controlled CL-SCS than OL-SCS. TRIAL REGISTRATION NUMBER: NCT02924129.

Holistic Treatment Response: An International Expert Panel Definition and Criteria for a New Paradigm in the Assessment of Clinical Outcomes of Spinal Cord Stimulation.

BACKGROUND: Treatment response to spinal cord stimulation (SCS) is focused on the magnitude of effects on pain intensity. However, chronic pain is a multidimensional condition that may affect individuals in different ways and as such it seems reductionist to evaluate treatment response based solely on a unidimensional measure such as pain intensity. AIM: The aim of this article is to add to a framework started by IMMPACT for assessing the wider health impact of treatment with SCS for people with chronic pain, a "holistic treatment response". DISCUSSION: Several aspects need consideration in the assessment of a holistic treatment response. SCS device data and how it relates to patient outcomes, is essential to improve the understanding of the different types of SCS, improve patient selection, long-term clinical outcomes, and reproducibility of findings. The outcomes to include in the evaluation of a holistic treatment response need to consider clinical relevance for patients and clinicians. Assessment of the holistic response combines two key concepts of patient assessment: (1) patients level of baseline (pre-treatment) unmet need across a range of health domains; (2) demonstration of patient-relevant improvements in these health domains with treatment. The minimal clinical important difference (MCID) is an established approach to reflect changes after a clinical intervention that are meaningful for the patient and can be used to identify treatment response to each individual domain. A holistic treatment response needs to account for MCIDs in all domains of importance for which the patient presents dysfunctional scores pre-treatment. The number of domains included in a holistic treatment response may vary and should be considered on an individual basis. Physiologic confirmation of therapy delivery and utilisation should be included as part of the evaluation of a holistic treatment response and is essential to advance the field of SCS and increase transparency and reproducibility of the findings.

Healthcare Utilization and Costs Associated with New-Onset Pain in a Medicare Population.

BACKGROUND: Chronic pain is a common and growing problem in the United States with variable strategies for its treatment. Surgical interventions are necessary in some cases but not required for all patients with new-onset pain. For some patients, interventional pain management (IPM) techniques can treat chronic pain without the cost or risk associated with surgical intervention. OBJECTIVE: The objective of this study was to compare healthcare utilization and costs for new-onset chronic pain treated by IPM specialists to those treated by providers with surgical specialties (i.e., orthopedists and neurosurgeons). STUDY DESIGN: This was a retrospective observational study of qualifying patients over 36-months (2016-2019). SETTING: This study was conducted using 100% Medicare FFS Parts A, B, and Prescription Drug Event (PDE) Part D data, including enrollment and claims. METHODS: Patients with a diagnosis of pain were identified in the claims data. Twelve months of pre-period claims were examined to ensure the incident diagnosis of pain, and 2 additional pain diagnoses were required after initial diagnosis. Patients were assigned either to the IPM cohort or a Surgical cohort based on the specialty of the provider involved in their first pain-related visit after initial diagnosis. Key outcomes, such as the utilization of healthcare services and cost of care, were evaluated for both cohorts over the 24-months following the index diagnosis of pain. RESULTS: 106,658 beneficiaries were included in the study with roughly 36% in the IPM cohort. Patients in the IPM cohort were less healthy and had lower incomes in the baseline period compared to the Surgical cohort. Fewer members of the IPM cohort had an inpatient stay in the 24-months post index pain diagnosis (40% compared to 43% in the surgery cohort) and the IPM cohort had fewer patients with a post-acute care stay (29% compared to 31% in the inpatient stay cohort). The IPM cohort had lower risk-adjusted total costs of care than the Surgical cohort, driven by lower inpatient, outpatient, and post-acute care costs. LIMITATIONS: Retrospective claims data may not include some factors important to patients with a pain diagnosis (such as over-the-counter medications, holistic treatments, or pain scores). CONCLUSION(S): By shifting patients from higher-cost and more invasive surgical procedures, IPM's multidisciplinary approach to pain treatment can reduce surgical utilization and costs for certain chronic pain patients. This shift away from more expensive surgical treatments fits well with Medicare's move toward value-based care, driven by a focus on patient outcomes including health care utilization and costs.

Trial Design and Endpoint Evaluation in Clinical Studies Addressing Chronic Back Pain.

STUDY DESIGN: A review of the literature evaluating clinical trials of chronic back pain. OBJECTIVE: To assist physicians in assessing the quality of clinical trial data to make the most informed treatment decisions. SUMMARY OF BACKGROUND DATA: Chronic pain is a tremendous public health issue, affecting close to 100 million adults in the United States, and costs the American people billions of dollars. One traditional treatment approach, the long-term use of opiate medications, has recently come under intense scrutiny for problems with complications, diversion, abuse, addiction, and lack of efficacy. In addition, the Centers for Disease Control and Prevention has recognized that overprescribing opiates has enabled an overdose crisis, and written guidelines that are intended to limit their use. It is for this reason that physicians must have a comprehensive understanding of the range of drug-free alternative therapies available and have the tools needed to rigorously evaluate the chronic pain literature so they can make appropriate treatment decisions. METHODS: An evaluation of how clinical trials are designed and ranked, outcome measures, and costs for a variety of therapies is necessary to determine which treatment option is the most efficacious for an individual patient. RESULTS: Clinical trial data demonstrate that spinal cord stimulation (SCS) is a safe and effective treatment option for many types of chronic pain, including back pain. The last 10 years has brought tremendous advances in the field of neuromodulation. Today, several treatment modalities exist for SCS requiring the physician to be able to critically evaluate and interpret the literature and determine which modality has the strongest evidence. When evaluating clinical trial data of patients with chronic back pain, emphasis must be placed on well designed, randomized controlled trials with long-term follow-up producing level I evidence. These data are obtained in a rigorous manner and are likely to have less bias when compared with lower level studies. CONCLUSION: The level I studies performed to date have provided evidence that treatment with SCS results in sustainable pain reduction and improvements in scores measuring quality of life and patient functioning in those patients with chronic intractable back pain. LEVEL OF EVIDENCE: 5.

Review of occupational medicine practice guidelines for interventional pain management and potential implications.

In the modern day environment, workers' compensation costs continue to be a challenge, with a need to balance costs, benefits, and quality of medical care. The cost of workers' compensation care affects all stakeholders including workers, employers, providers, regulators, legislators, and insurers. Consequently, a continued commitment to quality, accessibility to care, and cost containment will help ensure that workers are afforded accessible, high quality, and cost-effective care. In 2004, workers' compensation programs in all 50 states, the District of Columbia, and federal programs in the United States combined received an income of $87.4 billion while paying out only $56 billion in medical and cash benefits with $31.4 billion or 37% in administrative expenses and profit. Occupational diseases represented only 8% of the workers' compensation claims and 29% of the cost. The American College of Occupational and Environmental Medicine (ACOEM) has published several guidelines; though widely adopted by WCPs, these guidelines evaluate the practice of medicine of multiple specialties without adequate expertise and expert input from the concerned specialties, including interventional pain management. An assessment of the ACOEM guidelines utilizing Appraisal of Guidelines for Research and Evaluation (AGREE) criteria, the criteria developed by the American Medical Association (AMA), the Institute of Medicine (IOM), and other significantly accepted criteria, consistently showed very low scores (< 30%) in most aspects of the these guidelines. The ACOEM recommendations do not appear to have been based on a careful review of the literature, overall quality of evidence, standard of care, or expert consensus. Based on the evaluation utilizing appropriate and current evidence-based medicine (EBM) principles, the evidence ratings for diagnostic techniques of lumbar discography; cervical, thoracic, and lumbar facet joint nerve blocks and sacroiliac joint nerve blocks; therapeutic cervical and lumbar medial branch blocks and radiofrequency neurolysis; cervical interlaminar epidural steroid injections, caudal epidural steroid injections, and lumbar transforaminal epidural injections; caudal percutaneous adhesiolysis; abd spinal cord stimulation were found to be moderate with strong recommendation applying for most patients in most circumstances. The evidence ratings for intradiscal electrothermal therapy (IDET), an automated percutaneous disc decompression and also deserve further scrutiny and analysis. In conclusion, these ACOEM guidelines for interventional pain management have no applicability in modern patient care due to lack of expertise by the developing organization (ACOEM), lack of utilization of appropriate and current EBM principles, and lack of significant involvement of experts in these techniques resulting in a lack of clinical relevance. Thus, they may result in reduced medical quality of care; may severely hinder access to appropriate, medically needed and essential medical care; and finally, they may increase costs for injured workers, third party payors, and the government by transferring the injured worker into a non-productive disability system.

The psychological behaviorism theory of pain and the placebo: its principles and results of research application.

The psychological behaviorism theory of pain unifies biological, behavioral, and cognitive-behavioral theories of pain and facilitates development of a common vocabulary for pain research across disciplines. Pain investigation proceeds in seven interacting realms: basic biology, conditioned learning, language cognition, personality differences, pain behavior, the social environment, and emotions. Because pain is an emotional response, examining the bidirectional impact of emotion is pivotal to understanding pain. Emotion influences each of the other areas of interest and causes the impact of each factor to amplify or diminish in an additive fashion. Research based on this theory of pain has revealed the ameliorating impact on pain of (1) improving mood by engaging in pleasant sexual fantasies, (2) reducing anxiety, and (3) reducing anger through various techniques. Application of the theory to therapy improved the results of treatment of osteoarthritic pain. The psychological behaviorism theory of the placebo considers the placebo a stimulus conditioned to elicit a positive emotional response. This response is most powerful if it is elicited by conditioned language. Research based on this theory of the placebo that pain is ameliorated by a placebo suggestion and augmented by a nocebo suggestion and that pain sensitivity and pain anxiety increase susceptibility to a placebo.