Glossary of Neurostimulation Terminology: A Collaborative Neuromodulation Foundation, Institute of Neuromodulation, and International Neuromodulation Society Project.

OBJECTIVE: Consistent terminology is necessary to facilitate communication, but limited efforts have addressed this need in the neurostimulation community. We set out to provide a useful and updated glossary for our colleagues and prospective patients. MATERIALS AND METHODS: This collaborative effort of the Neuromodulation Foundation (NF), the Institute of Neuromodulation (IoN), and the International Neuromodulation Society (INS) expands a glossary first published in 2007 for spinal cord stimulation. Peripheral nerve, dorsal root ganglion, deep brain, and motor cortex stimulation have been added to our scope. Volunteers from the collaborating entities used a nominal group process, consensus development panels, and the Delphi technique to reach consensus on inclusion and definition of terms. We created a glossary suitable for print and for expansion on the websites of the collaborating entities, which will offer the possibility of explaining definitions for a general audience. We excluded proprietary and brand names but included terms that have attracted proprietary interest without becoming brands or trademarks. We made an effort to be inclusive while also being concise and economical with space. RESULTS: We identified and defined 91 terms for this print edition and created an accompanying list of acronyms. As appropriate, we provided figures to illustrate the definitions. CONCLUSIONS: Although we refer to the glossary presented herein as the print edition, it can of course be viewed and searched electronically. NF, IoN, and INS will continue to collaborate on expanded web editions that can include hyperlinks for internal and external navigation. We believe this glossary will benefit our growing field by facilitating communication and mitigating inappropriate use of neurostimulation terms.

Cost-Effectiveness Model Shows Superiority of Wireless Spinal Cord Stimulation Implantation Without a Separate Trial.

OBJECTIVE: We evaluated the cost-effectiveness of wireless spinal cord stimulation (Wireless SCS) with single stage "direct to permanent" implantation vs. screening with temporary electrodes and an external pulse generator followed by implantation of a system for long-term use (IPG SCS). MATERIALS AND METHODS: We created a cost model that takes a 2019 United States (U.S.) payer perspective and is based on IPG SCS cost models for subjects with chronic back and/or leg pain. Our six-month decision tree includes the screening trial period (success ≥50% relief) and leads to various levels of pain relief with or without complications for IPG SCS and Wireless SCS and without complications for conventional medical management (CMM). Every three months in the follow-on 15-year Markov model (with costs and quality-adjusted life years discounted 3.5% annually), subjects remain stable or transition to deteriorated health or death. Subjects who fail SCS receive CMM. After 60 Markov cycles, a 100,000-sample simulation reveals the impact of maximum willingness-to-pay (WTP) from $10,000 to $100,000 per quality-adjusted life year on net monetary benefit (NMB). Sensitivity analyses considered the impact of the Wireless SCS screening success rate, Wireless SCS device cost, and IPG SCS device longevity. RESULTS: Compared with IPG SCS, Wireless SCS offers higher clinical effectiveness at a lower cost and a higher NMB for our WTP thresholds and is, thus, dominant. Wireless SCS is also cost-effective compared with CMM. Results remain robust with 1) Wireless SCS screening success rates as low as 85% (dominant), 2) the cost of the Wireless SCS devices as high as $55,000 (cost-effective), and 3) IPG SCS devices lasting 12 years (dominant). CONCLUSIONS: In this model, compared with IPG SCS or with CMM, Wireless SCS is a superior strategy.

Postoperative Infections Associated With Prolonged Spinal Cord Stimulation Trial Duration (PROMISE RCT).

INTRODUCTION: In the PROMISE study, a multinational randomized controlled trial (RCT) of the effectiveness of spinal cord stimulation (SCS) with multicolumn surgical leads as a treatment of low back pain, clinicians followed their usual practice. An early, unplanned safety analysis revealed that the infection rate in Belgium (5/23), where trial duration was a median 21.5 days, was significantly higher than the 1/64 rate observed in the other study countries (median 5.8 days, p < 0.01). This report reviews infections observed in the PROMISE study after study completion. MATERIALS AND METHODS: For all infections related to SCS, we used descriptive statistics and tests of independent variables to analyze potentially contributing factors (age, sex, coexisting medical conditions, tobacco use, lead type, and trial duration) between subjects with infections versus those without. Cumulative incidence curves were created using the Kaplan-Meier method and compared between the two strata using a log-rank test. RESULTS: Among nine (5.2%) infections in 174 subjects trialed, the only significant contributing factor to infection was trial duration: median 21 days (range 3-56) for those with infection vs. six days (1-41) for those without (p = 0.001; Wilcoxon rank-sum test). The cumulative incidence of infection for subjects trialed >10 days was 24.1% vs. 1.4% for subjects trialed ≤10 days (p < 0.001). After the protocol was amended to limit trial duration to 10 days, 14 infection-free trials were performed in Belgium. CONCLUSIONS: Although not part of the preplanned analysis, our observation supports the hypothesis of a cause-effect relationship between trial duration and the risk of infection and the conclusion that prolonged SCS trials should be avoided.

WIKISTIM.org: An On-Line Database of Published Neurostimulation Studies.

INTRODUCTION: Primary data reported in scientific publications provide guidance for improving patient care, expanding indications, identifying research gaps, educating patients, justifying reimbursement, and gaining regulatory approval. Finding and analyzing pertinent publications among the huge volume noted in databases such as PUBMED, however, costs time and effort. This situation demands innovative ways to locate citations of (and the possibility of abstracting data from) papers reporting primary findings. METHODS: We created WIKISTIM.org, a searchable easily navigated website, to meet this challenge in our field and devised a taxonomy of data categories specific for various stimulation targets for extracting and posting primary data. We included a discussion section unlimited by time or space to overcome limits posed by traditional letters to the editor. RESULTS: Registrants can download single or multiple citations from search results or from the list of papers (sortable by author, title, publication, and year) into a single table. The downloadable data category lists are used to submit completed data entry sheets for upload and for evidence-based comparison across studies as well as for study design, manuscript preparation, and peer review. Registration for WIKISTIM access continues to grow as do the curated citation lists, which are updated monthly and are comprehensive for deep brain stimulation, dorsal root ganglion stimulation, gastric electric stimulation, spinal cord stimulation, and sacral nerve stimulation. CONCLUSIONS: Most WIKISTIM entries are limited to citation information and links to published abstracts. As the number of completed datasheets and of stimulation target sections increase, the value of WIKISTIM will increase.

A review of economic factors related to the delivery of health care for chronic low back pain.

INTRODUCTION AND METHODS: We describe tools used to evaluate the economic impact of health care interventions, discuss the economic burden of chronic low back pain, and review evidence on the cost-effectiveness of treating failed back surgery syndrome with spinal cord stimulation, intrathecal drug delivery, acupuncture, epidural injections, disc prosthesis, lumbar fusion, and noninvasive therapies. We also mention the lack of cost studies for emerging therapies, such as vibrotherapy and peripheral nerve field stimulation. Topics include types of cost studies; the economic perspectives taken by such studies; direct and indirect costs; measures of success; definitions of cost-effectiveness, incremental cost-effectiveness, incremental cost-utility ratios, and quality-adjusted life years; the concept of maximum willingness to pay; and the use of cost-effectiveness models. CONCLUSION: The fact that chronic low back pain arises from a variety of causes makes choosing appropriate treatment difficult. Determining the cost-effectiveness of various treatments for chronic low back pain depends on well-designed and well-executed randomized controlled trials with parallel economic evaluations. Researchers can use economic models to extrapolate costs and outcomes over the long term.

Prevention of percutaneous spinal cord stimulation electrode migration: a 15-year experience.

OBJECTIVES: Percutaneous spinal cord stimulation electrodes have a propensity to migrate longitudinally, which is a costly complication that often compromises therapeutic effect. After implementing simple changes to our percutaneous electrode anchoring technique, we no longer encounter this migration. The current retrospective study updates previously reported results. MATERIALS AND METHODS: We retrospectively examined data in a consecutive series of patients in whom we had secured a new percutaneous electrode by injecting < 0.1 cm(3) of adhesive into the silicone elastomer lead anchor. From 1998 through 2006, we used whichever anchor was supplied with each lead until we observed one case of migration through a short anchor; thereafter, we used a long, tapered anchor exclusively. From 2007 through 2013, we further modified our technique by adding a fascial incision to accommodate the tip of the anchor and by increasing the strength of our suture material. RESULTS: In the first series of 291 patients, followed through July 2007 (mean 4.75 years, range 1.1-9.0 years), 4 (1.37%) experienced electrode migration requiring surgical revision. Only one lead had moved with respect to its anchor; the other three anchors remained securely bonded to their leads. No migration (0.00%) occurred in the second series of 142 patients, followed through 2013 (mean follow-up 2.86 years, range 0.10-5.45 years). CONCLUSION: Improvements to our simple, inexpensive technique apparently have eliminated the most common complication of spinal cord stimulation.

Incidence and avoidance of neurologic complications with paddle type spinal cord stimulation leads.

INTRODUCTION: While reference is frequently made to the risk of spinal cord or nerve root injury with the surgical implantation of paddle type spinal cord stimulation (SCS) electrodes, data are lacking on the frequency, causes, and prevention of these complications. METHODS: To determine the incidence and frequency of neurologic complications, we performed 1) a comprehensive analysis of the literature to determine the incidence of complications that have caused or could lead to neurologic injury; 2) an analysis of the US Food and Drug Administration Manufacturer and User Facility Device Experience (MAUDE) data base; and 3) an investigation of manufacturers' data on surgically implanted paddle electrodes. We then convened an expert panel of neurosurgeons experienced in the surgical implantation of paddle electrodes to provide recommendations to minimize the risk of neurologic injury. RESULTS: The scientific literature describes the breadth of neurologic complications that can result from SCS electrode implantation but does not provide interpretable data with respect to the incidence and frequency of these complications. The MAUDE data base is not constructed to be sensitive or specific enough to provide these critical data. Primary data show a risk of neurologic injury from implantation of paddle electrodes below 0.6%. DISCUSSION: Preoperative, intraoperative, and postoperative measures to further minimize this risk are described. CONCLUSIONS: This investigation, the first comprehensive evaluation of the incidence and frequency of neurologic injury as a result of SCS paddle electrode implantation, suggests that neurologic injury is a rare, but serious, complication of SCS. The incidence of these complications should be decreased by the adoption of approaches that improve procedural safety and by careful patient follow-up and complication management. Physicians should be aware of these approaches and take every precaution to reduce the risk of neurologic injury. Physicians also should report any adverse event leading to injury or death and work together to improve access to these data.

Spinal cord stimulation versus re-operation in patients with failed back surgery syndrome: an international multicenter randomized controlled trial (EVIDENCE study).

OBJECTIVE: This paper presents the protocol of the EVIDENCE study, a multicenter multinational randomized controlled trial to assess the effectiveness and cost-effectiveness of spinal cord stimulation (SCS) with rechargeable pulse generator versus re-operation through 36-month follow-up in patients with failed back surgery syndrome. STUDY DESIGN: Study subjects have neuropathic radicular leg pain exceeding or equaling any low back pain and meet specified entry criteria. One-to-one randomization is stratified by site and by one or more prior lumbosacral operations. The sample size of 132 subjects may be adjusted to between 100 and 200 subjects using a standard adaptive design statistical method with pre-defined rules. Crossover treatment is possible. Co-primary endpoints are proportion of subjects reporting ≥ 50% leg pain relief without crossover at 6 and at 24 months after SCS screening trial or re-operation. Insufficient pain relief constitutes failure of randomized treatment, as does crossover. Secondary endpoints include cost-effectiveness; relief of leg, back, and overall pain; change in disability and quality of life; and rate of crossover. We are collecting data on subject global impression of change, patient satisfaction with treatment, employment status, pain/paresthesia overlap, SCS programming, and adverse events. DISCUSSION: As the first multicenter randomized controlled trial of SCS versus re-operation and the first to use only rechargeable SCS pulse generators, the EVIDENCE study will provide up-to-date evidence on the treatment of failed back surgery syndrome.

Research design considerations for randomized controlled trials of spinal cord stimulation for pain: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials/Institute of Neuromodulation/International Neuromodulation Society recommendations.

ABSTRACT: Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization overcomes certain types of bias, additional challenges to the validity of RCTs of SCS include blinding, choice of control groups, nonspecific effects of treatment variables (eg, paresthesia, device programming and recharging, psychological support, and rehabilitative techniques), and safety considerations. To address these challenges, 3 professional societies (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, Institute of Neuromodulation, and International Neuromodulation Society) convened a meeting to develop consensus recommendations on the design, conduct, analysis, and interpretation of RCTs of SCS for chronic pain. This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines.

Spinal cord stimulation for predominant low back pain in failed back surgery syndrome: study protocol for an international multicenter randomized controlled trial (PROMISE study).

BACKGROUND: Although results of case series support the use of spinal cord stimulation in failed back surgery syndrome patients with predominant low back pain, no confirmatory randomized controlled trial has been undertaken in this patient group to date. PROMISE is a multicenter, prospective, randomized, open-label, parallel-group study designed to compare the clinical effectiveness of spinal cord stimulation plus optimal medical management with optimal medical management alone in patients with failed back surgery syndrome and predominant low back pain. METHOD/DESIGN: Patients will be recruited in approximately 30 centers across Canada, Europe, and the United States. Eligible patients with low back pain exceeding leg pain and an average Numeric Pain Rating Scale score ≥5 for low back pain will be randomized 1:1 to spinal cord stimulation plus optimal medical management or to optimal medical management alone. The investigators will tailor individual optimal medical management treatment plans to their patients. Excluded from study treatments are intrathecal drug delivery, peripheral nerve stimulation, back surgery related to the original back pain complaint, and experimental therapies. Patients randomized to the spinal cord stimulation group will undergo trial stimulation, and if they achieve adequate low back pain relief a neurostimulation system using the Specify® 5-6-5 multi-column lead (Medtronic Inc., Minneapolis, MN, USA) will be implanted to capture low back pain preferentially in these patients. Outcome assessment will occur at baseline (pre-randomization) and at 1, 3, 6, 9, 12, 18, and 24 months post randomization. After the 6-month visit, patients can change treatment to that received by the other randomized group. The primary outcome is the proportion of patients with ≥50% reduction in low back pain at the 6-month visit. Additional outcomes include changes in low back and leg pain, functional disability, health-related quality of life, return to work, healthcare utilization including medication usage, and patient satisfaction. Data on adverse events will be collected. The primary analysis will follow the intention-to-treat principle. Healthcare use data will be used to assess costs and long-term cost-effectiveness. DISCUSSION: Recruitment began in January 2013 and will continue until 2016. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01697358 (http://www.clinicaltrials.gov).

Spinal cord stimulation versus reoperation for failed back surgery syndrome: a cost effectiveness and cost utility analysis based on a randomized, controlled trial.

OBJECTIVE: We analyzed the cost-effectiveness and cost-utility of treating failed back-surgery syndrome using spinal cord stimulation (SCS) versus reoperation. MATERIALS AND METHODS: A disinterested third party collected charge data for the first 42 patients in a randomized controlled crossover trial. We computed the difference in cost with regard to success (cost-effectiveness) and mean quality-adjusted life years (cost-utility). We analyzed the patient-charge data with respect to intention to treat (costs and outcomes as a randomized group), treated as intended (costs as randomized; crossover failure assigned to a randomized group), and final treatment costs and outcomes. RESULTS: By mean 3.1-year follow-up, 13 of 21 patients (62%) crossed from reoperation versus 5 of 19 patients (26%) who crossed from SCS (P < 0.025) [corrected]. The mean cost per success was US $117,901 for crossovers to SCS. No crossovers to reoperation achieved success despite a mean per-patient expenditure of US $260,584. The mean per-patient costs were US $31,530 for SCS versus US $38,160 for reoperation (intention to treat), US $48,357 for SCS versus US $105,928 for reoperation (treated as intended), and US $34,371 for SCS versus US $36,341 for reoperation (final treatment). SCS was dominant (more effective and less expensive) in the incremental cost-effectiveness ratios and incremental cost-utility ratios. A bootstrapped simulation for incremental costs and quality-adjusted life years confirmed SCS's dominance, with approximately 72% of the cost results occurring below US policymakers' "maximum willingness to pay" threshold. CONCLUSION: SCS was less expensive and more effective than reoperation in selected failed back-surgery syndrome patients, and should be the initial therapy of choice. SCS is most cost-effective when patients forego repeat operation. Should SCS fail, reoperation is unlikely to succeed.