Consideraciones del diseño en investigación para ensayos controlados aleatorios de estimulación de la médula espinal para el dolor: recomendaciones de la iniciativa sobre métodos, medición y evaluación del dolor en ensayos clínicos/Instituto de Neuromodulación/Sociedad Internacional de Neuromodulación: Publicado originalmente en la Revista Pain. 2021; 162(37): 1935-1956. Traducción: Dr. Francisco Rivera

Nathaniel Katz; Robert H. Dworkin; Richard North; Simon Thomson; Sam Eldabe; Salim M. Hayek; Brian H. Kopell; John Markman; Ali Rezai; Rod S. Taylor; Dennis C. Turk; Eric Buchser; Howard Fields; Gregory Fiore; McKenzie Ferguson; Jennifer Gewandter; Chris Hilker; Roshini Jain; Angela Leitner; John Loeser; Ewan McNicol; Turo Nurmikko; Jane Shipley; Rahul Singh; Andrea Trescot; Robert van Dongen; Lalit Venkatesan

doi:10.47924/neurotarget2022124

Authors

Nathaniel Katz WCG Analgesic Solutions, Wayland, MA, USA.
Robert H. Dworkin University of Rochester, Rochester, NY, United States.
Richard North Johns Hopkins University.
Simon Thomson Basildon and Thurrock University Hospitals.
Sam Eldabe Exeter and Durham Universities.
Salim M. Hayek Case Western Reserve University
Brian H. Kopell Mount Sinai Health System
John Markman University of Rochester, Rochester, NY, United States.
Ali Rezai West Virginia University School of Medicine.
Rod S. Taylor University of Exeter
Dennis C. Turk University of Washington.
Eric Buchser EHCHospital, Morges, Switzerland.
Howard Fields University of California San Francisco.
Gregory Fiore Institute of Neuromodulation.
McKenzie Ferguson Southern Illinois University.
Jennifer Gewandter University of Rochester, Rochester, NY, United States.
Chris Hilker Medtronic.
Roshini Jain Boston Scientific
Angela Leitner Saluda.
John Loeser University of Washington.
Ewan McNicol MCPHS University
Turo Nurmikko University of Liverpool.
Jane Shipley The Neuromodulation Foundation.
Rahul Singh Washington University.
Andrea Trescot Stimwave
Robert van Dongen Radboud University Medical Centre.
Lalit Venkatesan Abbott

DOI:

https://doi.org/10.47924/neurotarget2022124

Keywords:

Spinal cord stimulation, Medical devices, Randomized controlled trials, Clinical trials, Clinical research methods

Abstract

Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for Narrative Review evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization over-comes 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 recommenda-tions 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.

Metrics

Metrics Loading ...

References

Al-Kaisy A, Palmisani S, Pang D, Sanderson K, Wesley S, Tan Y, McCammon S, Trescot A. Prospective, randomized, sham-control, double blind, crossover trial of subthreshold spinal cord stimulation at various kilohertz frequencies in subjects suffering from failed back surgery syndrome (SCS frequency study). Neuromodulation 2018;21: 457–65.

Babu R, Hazzard MA, Huang KT, Ugiliweneza B, Patil CG, Boakye M, Lad SP. Outcomes of percutaneous and paddle lead implantation for spinal cord stimulation: a comparative analysis of complications, reoperation rates, and health-care costs. Neuromodulation 2013;16: 418–26; discussion 426-427.

BarthJ,KernA,Lu ̈thiS,WittCM.Assessmentofpatients’expectations: development and validation of the Expectation for Treatment Scale (ETS). BMJ Open 2019;9:e026712.

Bir SC, Konar S, Maiti T, Nanda A, Guthikonda B. Neuromodulation in intractable pain management: outcomes and predictors of revisions of spinal cord stimulators. Neurosurg Focus 2016;40:E4.

Bishop GH. The relation between nerve fiber size and sensory modality: phylogenetic implications of the afferent innervation of cortex. J Nerv Ment Dis 1959;128:89–114.

Blaschke TF, Osterberg L, Vrijens B, Urquhart J. Adherence to medications: insights arising from studies on the unreliable link between prescribed and actual drug dosing histories. Annu Rev Pharmacol Toxicol 2012;52:275–301.

Bower P, Brueton V, Gamble C, Treweek S, Smith CT, Young B, Williamson P. Interventions to improve recruitment and retention in clinical trials: a survey and workshop to assess current practice and future priorities. Trials 2014;15:399.

Breckenridge A, Aronson JK, Blaschke TF, Hartman D, Peck CC, Vrijens B. Poor medication adherence in clinical trials: consequences and solutions. Nat Rev Drug Discov 2017;16:149–50.

Brummett CM, Bakshi RR, Goesling J, Leung D, Moser SE, Zollars JW, Williams DA, Clauw DJ, Hassett AL. Preliminary validation of the Michigan body map. PAIN 2016;157:1205–12.

Budd K. Spinal cord stimulation: cost-benefit study. Neuromodulation 2002;5:75–8.

Caylor J, Reddy R, Yin S, Cui C, Huang M, Huang C, Ramesh R, Baker DG, Simmons A, Souza D, Narouze S, Vallejo R, Lerman I. Spinal cord stimulation in chronic pain: evidence and theory for mechanisms of action. Bioelectron Med 2019;5:12.

CEBM. Oxford centre for evidence-based medicine—levels of evidence (March 2009). CEBM 2009. Available at: https://www.cebm.net/2009/06/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/ Accessed April 8, 2020.

Chen P-HA, Cheong JH, Jolly E, Elhence H, Wager TD, Chang LJ. Socially transmitted placebo effects. Nat Hum Behav 2019;3:1295–305.

Cohen J. Things I have learned (so far). Am Psychol 1990;45:1304–12.

De Andres J, Monsalve-Dolz V, Fabregat-Cid G, Villanueva-Perez V, Harutyunyan A, Asensio-Samper JM, Sanchis-Lopez N. Prospective, randomized blind effect-on-outcome study of conventional vs high- frequency spinal cord stimulation in patients with pain and disability due to failed back surgery syndrome. Pain Med Malden Mass 2017;18:2401–21.

De Jaeger M, van Hooff R-J, Goudman L, Valenzuela Espinoza A, Brouns R, Puylaert M, Duyvendak W, Moens M. High-density in spinal PAIN® cord stimulation: virtual expert registry (DISCOVER): study protocol for a prospective observational trial. Anesthesiol Pain Med 2017;7:e13640.

Deer TR, Jain S, Hunter C, Chakravarthy K. Neurostimulation for intractable chronic pain. Brain Sci 2019;9:23.

Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Leong M, Levy RM, Abejon D, Buchser E, Burton A, Buvanendran A, Candido K, Caraway D, Cousins M, DeJongste M, Diwan S, Eldabe S, Gatzinsky K, Foreman RD, Hayek S, Kim P, Kinfe T, Kloth D, Kumar K, Rizvi S, Lad SP, Liem L, Linderoth B, Mackey S, McDowell G, McRoberts P, Poree L, Prager J, Raso L, Rauck R, Russo M, Simpson B, Slavin K, Staats P, Stanton-Hicks M, Verrills P, Wellington J, Williams K, North R, Neuromodulation Appropriateness Consensus Committee. The appropriate use of neurostimulation of the spinal cord and peripheral nervous system for the treatment of chronic pain and ischemic diseases: the Neuromodulation Appropriateness Consensus Committee. Neuromodulation 2014;17:515–50; discussion 550.

Deer TR, Mekhail N, Provenzano D, Pope J, Krames E, Thomson S, Raso L, Burton A, DeAndres J, Buchser E, Buvanendran A, Liem L, Kumar K, Rizvi S, Feler C, Abejon D, Anderson J, Eldabe S, Kim P, Leong M, Hayek S, McDowell G, Poree L, Brooks ES, McJunkin T, Lynch P, Kapural L, Foreman RD, Caraway D, Alo K, Narouze S, Levy RM, North R; Neuromodulation Appropriateness Consensus Committee. The appropriate use of neurostimu-lation: avoidance and treatment of complications of neurostimulation therapies for the treatment of chronic pain. Neuromodulation Appropriateness Consensus Committee. Neuromodulation 2014;17:571–97; discussion 597-598.

Deer TR, Provenzano DA, Hanes M, Pope JE, Thomson SJ, Russo MA, McJunkin T, Saulino M, Raso LJ, Lad SP, Narouze S, Falowski SM, Levy RM, Baranidharan G, Golovac S, Demesmin D, Witt WO, Simpson B, Krames E, Mekhail N. The neurostimulation appropriateness consensus committee (NACC) recommendations for infection prevention and management. Neuromodulation 2017;20:31–50.

Devine EG, Peebles KR, Martini V. Strategies to exclude subjects who conceal and fabricate information when enrolling in clinical trials. Contemp Clin Trials Commun 2017;5:67–71.

Devine EG, Waters ME, Putnam M, Surprise C, O’Malley K, Richambault C, Fishman RL, Knapp CM, Patterson EH, Sarid-Segal O, Streeter C, Colanari L, Ciraulo DA. Concealment and fabrication by experienced research subjects. Clin Trials Lond Engl 2013;10:935–48.

Dickenson AH. Gate control theory of pain stands the test of time. Br J Anaesth 2002;88:755–7.

Duarte RV, McNicol E, Colloca L, Taylor RS, North RB, Eldabe S. Randomized placebo-sham-controlled trials of spinal cord stimulation: a systematic review and methodological appraisal. Neuromodulation 2020;23:10-18.

Dworkin JD, McKeown A, Farrar JT, Gilron I, Hunsinger M, Kerns RD, McDermott MP, Rappaport BA, Turk DC, Dworkin RH, Gewandter JS. Deficiencies in reporting of statistical methodology in recent randomized trials of nonpharmacologic pain treatments: ACTTION systematic review. J Clin Epidemiol 2016;72:56–65.

Dworkin RH. Two very different types of clinical importance. Contemp Clin Trials 2016;46:11.

Dworkin RH, Peirce-Sandner S, Turk DC, McDermott MP, Gibofsky A, Simon LS, Farrar JT, Katz NP. Outcome measures in placebo-controlled trials of osteoarthritis: responsiveness to treatment effects in the REPORT database. Osteoarthritis Cartilage 2011;19:483–92.

Dworkin RH, Turk DC, Farrar JT, Haythornthwaite JA, Jensen MP, Katz NP, Kerns RD, Stucki G, Allen RR, Bellamy N, Carr DB, Chandler J, Cowan P, Dionne R, Galer BS, Hertz S, Jadad AR, Kramer LD, Manning DC, Martin S, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robbins W, Robinson JP, Rothman M, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Wernicke J, Witter J, IMMPACT. Core outcome measures for chronic pain clinical trials: IMMPACT recommendations. PAIN 2005;113:9–19.

Dworkin RH, Turk DC, Katz NP, Rowbotham MC, Peirce-Sandner S, Cerny I, Clingman CS, Eloff BC, Farrar JT, Kamp C, McDermott MP, Rappaport BA, Sanhai WR. Evidence-based clinical trial design for chronic pain pharmacotherapy: a blueprint for ACTION. PAIN 2011;152: S107–15.

Dworkin RH, Turk DC, McDermott MP, Peirce-Sandner S, Burke LB, Cowan P, Farrar JT, Hertz S, Raja SN, Rappaport BA, Rauschkolb C, Sampaio C. Interpreting the clinical importance of group differences in chronic pain clinical trials: IMMPACT recommendations. PAIN 2009; 146:238–44.

Dworkin RH, Turk DC, Peirce-Sandner S, Baron R, Bellamy N, Burke LB, Chappell A, Chartier K, Cleeland CS, Costello A, Cowan P, Dimitrova R, Ellenberg S, Farrar JT, French JA, Gilron I, Hertz S, Jadad AR, Jay GW, Kallioma ̈ki J, Katz NP, Kerns RD, Manning DC, McDermott MP, McGrath PJ, Narayana A, Porter L, Quessy S, Rappaport BA, Rauschkolb C, Reeve BB, Rhodes T, Sampaio C, Simpson DM, Stauffer JW, Stucki G, Tobias J, White RE, Witter J. Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. PAIN 2010;149:177–93.

Dworkin RH, Turk DC, Peirce-Sandner S, Burke LB, Farrar JT, Gilron I, Jensen MP, Katz NP, Raja SN, Rappaport BA, Rowbotham MC, Backonja M-M, Baron R, Bellamy N, Bhagwagar Z, Costello A, Cowan P, Fang WC, Hertz S, Jay GW, Junor R, Kerns RD, Kerwin R, Kopecky EA, Lissin D, Malamut R, Markman JD, McDermott MP, Munera C, Porter L, Rauschkolb C, Rice ASC, Sampaio C, Skljarevski V, Sommerville K, Stacey BR, Steigerwald I, Tobias J, Trentacosti AM, Wasan AD, Wells GA, Williams J, Witter J, Ziegler D. Considerations for improving assay sensitivity in chronic pain clinical trials: IMMPACT recommendations. PAIN 2012;153:1148–58.

Edwards RR, Dworkin RH, Turk DC, Angst MS, Dionne R, Freeman R, Hansson P, Haroutounian S, Arendt-Nielsen L, Attal N, Baron R, Brell J, Bujanover S, Burke LB, Carr D, Chappell AS, Cowan P, Etropolski M, Fillingim RB, Gewandter JS, Katz NP, Kopecky EA, Markman JD, Nomikos G, Porter L, Rappaport BA, Rice ASC, Scavone JM, Scholz J, Simon LS, Smith SM, Tobias J, Tockarshewsky T, Veasley C, Versavel M, Wasan AD, Wen W, Yarnitsky D. Patient phenotyping in clinical trials of chronic pain treatments: IMMPACT recommendations. PAIN 2016; 157:1851–71.

Eldabe S, Buchser E, Duarte RV. Complications of spinal cord stimulation and peripheral nerve stimulation techniques: a review of the literature. Pain Med 2016;17:325–36.

Eldabe S, Gulve A, Thomson S, Baranidharan G, Duarte R, Jowett S, Sandhu H, Chadwick R, Brookes M, Tariq A, Earle J, Bell J, Kansal A, Rhodes S, Taylor RS. Does a screening trial for spinal cord stimulation in patients with chronic pain of neuropathic origin have clinical utility and cost-effectiveness? (TRIAL-STIM study): study protocol for a randomised controlled trial. Trials 2018;19:633.

EMEA. Committee for medicinal products for human use (CHMP) guideline on the choice of the non-inferiority margin. Stat Med 2006;25: 1628–38.

EMEA/CHMP. Guideline on the clinical development of medicinal products intended for the treatment pain. 2016. Available at: https:// www.ema.europa.eu/en/clinical-development-medicinal-products-intended-treatment-pain. Accessed April 6, 2020.

Erickson DL. Percutaneous trial of stimulation for patient selection for implantable stimulating devices. J Neurosurg 1975;43:440–4.

Erickson DL, Long DM. Ten-year follow-up of dorsal column stimulation. advances in pain research and therapy. Vol. 5. New York: Raven Press, 1983. p. 583–9.

Butler S. Development and validation of the post-operative recovery index for measuring quality of recovery after surgery. J Anesth Clin Res 2012;3. doi:10.4172/2155-6148.1000267.

Farrar JT, Dworkin RH, Max MB. Use of the cumulative proportion of responders analysis graph to present pain data over a range of cut-off points: making clinical trial data more understandable. J Pain Symptom Manage 2006;31:369–77.ç

Farrar JT, Troxel AB, Haynes K, Gilron I, Kerns RD, Katz NP, Rappaport BA, Rowbotham MC, Tierney AM, Turk DC, Dworkin RH. Effect of variability in the 7-day baseline pain diary on the assay sensitivity of neuropathic pain randomized clinical trials: an ACTTION study. PAIN 2014;155:1622–31.

FDA. Design considerations for pivotal clinical investigations for medical devices. 2013. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/design-considerations-pivotal-clinical-investigations-medical-devices. Accessed March 14, 2021.

FDA. Enrichment strategies for clinical trials to support approval of human drugs and biological products. 2019. Available at: https://www. fda.gov/regulatory-information/search-fda-guidance-documents/enrichment-strategies-clinical-trials-support-approval-human-drugs- and-biological-products. Accessed March 14, 2021.

FDA. Financial disclosures by clinical investigators. 1998. Available at: https://www.fda.gov/science-research/clinical-trials-and-human-subject-protection/financial-disclosures-clinical-investigators. Accessed March 1, 2020.

FDA. Investigator responsibilities-protecting the rights, safety, and welfare of study subjects. 2009. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/investigator-responsibilities-protecting-rights-safety-and-welfare-study-subjects. Accessed March 14, 2021.

FDA. Non-inferiority clinical trials. 2016. Available at: https://www.fda. gov/regulatory-information/search-fda-guidance-documents/non-inferiority-clinical-trials. Accessed March 14, 2021.

FDA. Oversight of clinical investigations—a risk-based approach to monitoring. 2013. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/oversight-clinical-investigations-risk-based-approach-monitoring. Accessed March 14, 2021.

FDA. Patient-reported outcome measures: use in medical product development to support labeling claims. 2009. Available at: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/patient-reported-outcome-measures-use-medical-product-development-support-labeling-claims. Accessed March 14, 2021.

Follett KA, Boortz-Marx RL, Drake JM, DuPen S, Schneider SJ, Turner MS, Coffey RJ. Prevention and management of intrathecal drug delivery and spinal cord stimulation system infections. Anesthesiology 2004; 100:1582–94.

Freynhagen R, Baron R. The evaluation of neuropathic components in low back pain. Curr Pain Headache Rep 2009;13:185–90.

Gewandter JS, Eisenach JC, Gross RA, Jensen MP, Keefe FJ, Lee DA, Turk DC. Checklist for the preparation and review of pain clinical trial publications: a pain-specific supplement to CONSORT. Pain Rep 2019; 4:e621.

Gewandter JS, McDermott MP, Kitt RA, Chaudari J, Koch JG, Evans SR, Gross RA, Markman JD, Turk DC, Dworkin RH. Interpretation of CIs in clinical trials with non-significant results: systematic review and recommendations. BMJ Open 2017;7:e017288.

GewandterJS,McDermottMP,McKeownA,HoangK,IwanK,Kralovic S, Rothstein D, Gilron I, Katz NP, Raja SN, Senn S, Smith SM, Turk DC, Dworkin RH. Reporting of cross-over clinical trials of analgesic treatments for chronic pain: analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities, and Networks systematic review and recommendations. PAIN 2016;157:2544–51.

Gewandter JS, McDermott MP, McKeown A, Smith SM, Pawlowski JR, Poli JJ, Rothstein D, Williams MR, Bujanover S, Farrar JT, Gilron I, Katz NP, Rowbotham MC, Turk DC, Dworkin RH. Reporting of intention-to- treat analyses in recent analgesic clinical trials: ACTTION systematic review and recommendations. PAIN 2014;155:2714–19.

Gewandter JS, Smith SM, McKeown A, Burke LB, Hertz SH, Hunsinger M, Katz NP, Lin AH, McDermott MP, Rappaport BA, Williams MR, Turk DC, Dworkin RH. Reporting of primary analyses and multiplicity adjustment in recent analgesic clinical trials: ACTTION systematic review and recommendations. PAIN 2014;155:461–6.

Gluud LL. Bias in clinical intervention research. Am J Epidemiol 2006; 163:493–501.

Gracely RH, Dubner R, Wolskee PJ, Deeter WR. Placebo and naloxone can alter post-surgical pain by separate mechanisms. Nature 1983;306: 264–5.

Grady C, Cummings SR, Rowbotham MC, McConnell MV, Ashley EA, Kang G. Informed consent. N Engl J Med 2017;376:856–67.

Grider JS, Harned M. High-density spinal cord stimulation for the treatment of pain in the rehabilitation patient. In: Carayannopoulos A, editor. Comprehensive pain management in the rehabilitation patient. Cham: Springer International Publishing, 2017. p. 647–55.

Harris RE, Williams DA, McLean SA, Sen A, Hufford M, Gendreau RM, Gracely RH, Clauw DJ. Characterization and consequences of pain variability in individuals with fibromyalgia. Arthritis Rheum 2005;52: 3670–4.

Hayek SM, Veizi E, Hanes M. Treatment-limiting complications of percutaneous spinal cord stimulator implants: a review of eight years of experience from an academic center database. Neuromodulation 2015; 18:603–8; discussion 608-609.

HazlewoodGS.Measuringpatientpreferences:anoverviewofmethods with a focus on discrete choice experiments. Rheum Dis Clin North Am 2018;44:337–47.

Henderson JM, Levy RM, Bedder MD, Staats PS, Slavin KV, Poree LR, North RB. NANS training requirements for spinal cord stimulation devices: selection, implantation, and follow-up. Neuromodulation 2009; 12:171–4.

Higgins J, Altman D, Stern J, editors. . In: Cochrane handbook for systematic reviews of interventions. version 5.2.0. 2017. Available at: www.training.cochrane.org/handbook. Accessed March 14, 2021.

Hoffmann TC, Glasziou PP, Boutron I, Milne R, Perera R, Moher D, Altman DG, Barbour V, Macdonald H, Johnston M, Lamb SE, Dixon- Woods M, McCulloch P, Wyatt JC, Chan A-W, Michie S. Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide. BMJ 2014;348:g1687.

Hofmeister M, Memedovich A, Brown S, Saini M, Dowsett LE, Lorenzetti DL, McCarron TL, MacKean G, Clement F. Effectiveness of neurostimulation technologies for the management of chronic pain: a systematic review. Neuromodulation 2020;23:150–7.

Holsheimer J. Effectiveness of spinal cord stimulation in the management of chronic pain: analysis of technical drawbacks and solutions. Neurosurgery 1997;40:990–6; discussions 996-999.

Huang KT, Martin J, Marky A, Chagoya G, Hatef J, Hazzard MA, Thomas SM, Lokhnygina Y, Lad SP. A national survey of spinal cord stimulation trial-to-permanent conversion rates. Neuromodulation 2015;18:133–9; discussion 139-140.

ICH. E6(R2) good clinical practice: integrated addendum to ICH E6(R1). 2018. Available at: https://www.fda.gov/media/93884/download. Accessed March 14, 2021.

ICMJE. Uniform requirements for manuscripts submitted to biomedical journals: writing and editing for biomedical publication. J Pharmacol Pharmacother 2010;1:42–58.

Institute of Medicine (US) Committee on Advancing Pain Research, Care, and Education. Relieving pain in America: a blueprint for transforming prevention, care, education, and research. Washington (DC): National Academies Press (US), 2011. Available at: http://www. ncbi.nlm.nih.gov/books/NBK91497/. Accessed April 7, 2020.

ISO. ISO 14155:2011: clinical investigation of medical devices for human subjects—good clinical practice. Available at: https://www.iso. org/obp/ui/#iso:std:iso:14155:ed-2:v1:en.

JamisonRN,GracelyRH,RaymondSA,LevineJG,MarinoB,Herrmann TJ, Daly M, Fram D, Katz NP. Comparative study of electronic vs. paper VAS ratings: a randomized, crossover trial using healthy volunteers. PAIN 2002;99:341–7.

Jamison RN, Raymond SA, Levine JG, Slawsby EA, Nedeljkovic SS, Katz NP. Electronic diaries for monitoring chronic pain: 1-year validation study. PAIN 2001;91:277–85.

Kam-Hansen S, Jakubowski M, Kelley JM, Kirsch I, Hoaglin DC, Kaptchuk TJ, Burstein R. Altered placebo and drug labeling changes the outcome of episodic migraine attacks. Sci Transl Med 2014;6:218ra5.

Kaptchuk TJ. Open-label placebo: reflections on a research agenda. Perspect Biol Med 2018;61:311–34.

KapuralL,YuC,DoustMW,GlinerBE,VallejoR,SitzmanBT,Amirdelfan K, Morgan DM, Brown LL, Yearwood TL, Bundschu R, Burton AW, Yang T, Benyamin R, Burgher AH. Novel 10-kHz high-frequency therapy (HF10 therapy) is superior to traditional low-frequency spinal cord stimulation for the treatment of chronic back and leg pain: the SENZA- RCT randomized controlled trial. Anesthesiology 2015;123:851–60.

Katz J, Finnerup NB, Dworkin RH. Clinical trial outcome in neuropathic pain: relationship to study characteristics. Neurology 2008;70:263–72.

KatzNP.Themeasurementofsymptomsandsideeffectsinclinicaltrials of chronic pain. Contemp Clin Trials 2012;33:903–11.

KelleyJM,LemboAJ,AblonJS,VillanuevaJJ,ConboyLA,LevyR,Marci CD, Kerr CE, Kirsch I, Jacobson EE, Riess H, Kaptchuk TJ. Patient and practitioner influences on the placebo effect in irritable bowel syndrome. Psychosom Med 2009;71:789–97.

Kernan WN, Viscoli CM, Makuch RW, Brass LM, Horwitz RI. Stratified randomization for clinical trials. J Clin Epidemiol 1999;52:19–26.

Khan H, Pilitsis JG, Prusik J, Smith H, McCallum SE. Pain remission at one-year follow-up with spinal cord stimulation. Neuromodulation 2018; 21:101–5.

Kinfe TM, Quack F, Wille C, Schu S, Vesper J. Paddle versus cylindrical leads for percutaneous implantation in spinal cord stimulation for failed back surgery syndrome: a single-center trial. J Neurol Surg Part Cent Eur Neurosurg 2014;75:467–73.

Kobak KA, Leuchter A, DeBrota D, Engelhardt N, Williams JBW, Cook IA, Leon AC, Alpert J. Site versus centralized raters in a clinical depression trial: impact on patient selection and placebo response. J Clin Psychopharmacol 2010;30:193–7.

Kumar K, Hunter G, Demeria D. Spinal cord stimulation in treatment of chronic benign pain: challenges in treatment planning and present status, a 22-year experience. Neurosurgery 2006;58:481–96; discussion 481-496.

Kumar K, Rizvi S. Cost-effectiveness of spinal cord stimulation therapy in management of chronic pain. Pain Med Malden Mass 2013;14: 1631–49.

Kumar K, Taylor RS, Jacques L, Eldabe S, Meglio M, Molet J, Thomson S, O’Callaghan J, Eisenberg E, Milbouw G, Buchser E, Fortini G, Richardson J, North RB. Spinal cord stimulation versus conventional medical management for neuropathic pain: a multicentre randomised controlled trial in patients with failed back surgery syndrome. PAIN 2007; 132:179–88.

Kumar V, Prusik J, Lin Y, Hwang R, Feustel P, Pilitsis JG. Efficacy of alternating conventional stimulation and high frequency stimulation in improving spinal cord stimulation outcomes: a pilot study. Neuromodulation 2018;21:466–71.

Levy R, Deer TR, Poree L, Rosen SM, Kapural L, Amirdelfan K, Soliday N, Leitner A, Mekhail N. Multicenter, randomized, double-blind study protocol using human spinal cord recording comparing safety, efficacy, and neurophysiological responses between patients being treated with evoked compound action potential-controlled closed-loop spinal cord stimulation or open-loop spinal cord stimulation (the evoke study). Neuromodulation 2019;22:317–26.

Levy RM. Neuromodulation and the requirements for reporting of complications of implanted medical devices in the United States. Neuromodulation 2011;14:295–7.

LevyRM. Theneed for mechanism-based medicine in neuromodulation. Neuromodulation 2012;15:273–9.

Linde C, Curtis AB, Fonarow GC, Lee K, Little W, Tang A, Levya F, Momomura S, Manrodt C, Bergemann T, Cowie MR. Cardiac resynchronization therapy in chronic heart failure with moderately reduced left ventricular ejection fraction: lessons from the Multicenter InSync Randomized Clinical Evaluation MIRACLE EF study. Int J Cardiol 2016;202:349–55.

Linderoth B. Dorsal column stimulation and pain: experimental studies of putitive neurochemical and neurophysiological mechanisms. Stockholm: Karolinska Institute, 1992.

Linderoth B, Foreman RD. Conventional and novel spinal stimulation algorithms: hypothetical mechanisms of action and comments on outcomes. Neuromodulation 2017;20:525–33.

Markman J, Resnick M, Greenberg S, Katz N, Yang R, Scavone J, Whalen E, Gregorian G, Parsons B, Knapp L. Efficacy of pregabalin in post-traumatic peripheral neuropathic pain: a randomized, double- blind, placebo-controlled phase 3 trial. J Neurol 2018;265:2815–24.

Markman JD, Kress BT, Frazer M, Hanson R, Kogan V, Huang JH. Screening for neuropathic characteristics in failed back surgery syndromes: challenges for guiding treatment. Pain Med Malden Mass 2015;16:520–30.

Mathieson S, Maher CG, McLachlan AJ, Latimer J, Koes BW, Hancock MJ, Harris I, Day RO, Billot L, Pik J, Jan S, Lin C-WC. Trial of pregabalin for acute and chronic sciatica. N Engl J Med 2017;376:1111–20.

McKeown A, Gewandter JS, McDermott MP, Pawlowski JR, Poli JJ, Rothstein D, Farrar JT, Gilron I, Katz NP, Lin AH, Rappaport BA, Rowbotham MC, Turk DC, Dworkin RH, Smith SM. Reporting of sample size calculations in analgesic clinical trials: ACTTION systematic review. J Pain 2015;16:199–206.e1–7.

MeissnerK,Fa ̈sslerM,Ru ̈ckerG,KleijnenJ,Hro ́bjartssonA,Schneider A, Antes G, Linde K. Differential effectiveness of placebo treatments: a systematic review of migraine prophylaxis. JAMA Intern Med 2013;173: 1941–51.

MekhailN,LevyRM,DeerTR,KapuralL,LiS,AmirdelfanK,HunterCW, Rosen SM, Costandi SJ, Falowski SM, Burgher AH, Pope JE, Gilmore CA, Qureshi FA, Staats PS, Scowcroft J, Carlson J, Kim CK, Yang MI, Stauss T, Poree L; Evoke Study Group. Long-term safety and efficacy of closed-loop spinal cord stimulation to treat chronic back and leg pain (Evoke): a double-blind, randomised, controlled trial. Lancet Neurol 2020;19:123–34.

Mekhail NA, Mathews M, Nageeb F, Guirguis M, Mekhail MN, Cheng J. Retrospective review of 707 cases of spinal cord stimulation: indications and complications. Pain Pract Off J World Inst Pain 2011;11:148–53.

Melzack R, Wall PD. Pain mechanisms: a new theory. Science 1965; 150:971–9.

Meske DS, Vaughn BJ, Kopecky EA, Katz N. Number of clinical trial study sites impacts observed treatment effect size: an analysis of randomized controlled trials of opioids for chronic pain. J Pain Res 2019; 12:3161–5.

Moher D, Hopewell S, Schulz KF, Montori V, Gøtzsche PC, Devereaux PJ, Elbourne D, Egger M, Altman DG; CONSORT. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. Int J Surg Lond Engl 2012;10:28–55.

Nathan PW. The gate-control theory of pain. A critical review. Brain J Neurol 1976;99:123–58.

National Research Council (US) Panel on Handling Missing Data in Clinical Trials. The prevention and treatment of missing data in clinical trials. Washington (DC): National Academies Press (US), 2010. Available at: http://www.ncbi.nlm.nih.gov/books/NBK209904/. Accessed April 8, 2020.

NICE. Spinal cord stimulation for chronic pain of neuropathic or ischaemic origin: Technology appraisal guidance. 2008. Available at: https://www.nice.org.uk/guidance/ta159. Accessed April 8, 2020.

North RB, Calodney A, Bolash R, Slavin KV, Creamer M, Rauck R, Vahedifar P, FoxI, O ̈zaktay C, Panchal S, Vanquathem N. Redefining spinal cord stimulation “trials”: a randomized controlled trial using single- stage wireless permanent implantable devices. Neuromodulation 2020; 23:96–101.

NorthRB,FischellTA,LongDM.Chronicstimulationviapercutaneously inserted epidural electrodes. Neurosurgery 1977;1:215–18.

North RB, Kidd DH, Farrokhi F, Piantadosi SA. Spinal cord stimulation versus repeated lumbosacral spine surgery for chronic pain: a randomized, controlled trial. Neurosurgery 2005;56:98–106; discussion 106-107.

North RB, Kidd DH, Olin J, Sieracki JM, Boulay M. Spinal cord stimulation with interleaved pulses: a randomized, controlled trial. Neuromodulation 2007;10:349–57.

North RB, Kidd DH, Petrucci L, Dorsi MJ. Spinal cord stimulation electrode design: a prospective, randomized, controlled trial comparing percutaneous with laminectomy electrodes: part II-clinical outcomes. Neurosurgery 2005;57:990–6; discussion 990-996.

North RB, Parihar HS, Spencer SD, Spalding AF, Shipley J. Cost- effectiveness model shows superiority of wireless spinal cord stimulation implantation without a separate trial. Neuromodulation 2020. doi: 10.1111/ner.13102 [Epub ahead of print].

North RB, Shipley J. WIKISTIM.org: an on-line database of published neurostimulation studies. Neuromodulation 2018;21:828–36.

Odgaard-Jensen J, Vist GE, Timmer A, Kunz R, Akl EA, Schunemann H, Briel M, Nordmann AJ, Pregno S, Oxman AD. Randomisation to protect against selection bias in healthcare trials. Cochrane Database Syst Rev 2011:MR000012.

Osgood E, Trudeau JJ, Eaton TA, Jensen MP, Gammaitoni A, Simon LS, Katz N. Development of a bedside pain assessment kit for the classification of patients with osteoarthritis. Rheumatol Int 2015;35: 1005–13.

Paraschiv-Ionescu A, Buchser E, Aminian K. Unraveling dynamics of human physical activity patterns in chronic pain conditions. Sci Rep 2013;3:2019.

Paraschiv-Ionescu A, Perruchoud C, Rutschmann B, Buchser E, Aminian K. Quantifying dimensions of physical behavior in chronic pain conditions. J Neuroengineering Rehabil 2016;13:85.

Patient reported outcome measures (PROMs). Available at: https://www.england.nhs.uk/statistics/statistical-work-areas/proms/. Accessed April 28, 2020.

Perruchoud C, Eldabe S, Batterham AM, Madzinga G, Brookes M, Durrer A, Rosato M, Bovet N, West S, Bovy M, Rutschmann B, Gulve A, Garner F, Buchser E. Analgesic efficacy of high-frequency spinal cord stimulation: a randomized double-blind placebo-controlled study. Neuromodulation 2013;16:363–9; discussion 369.

Piaggio G, Elbourne DR, Pocock SJ, Evans SJW, Altman DG; CONSORT Group. Reporting of noninferiority and equivalence randomized trials: extension of the CONSORT 2010 statement. JAMA 2012;308:2594–604.

Pope JE, Falowski S, Deer TR. Advanced waveforms and frequency with spinal cord stimulation: burst and high-frequency energy delivery. Expert Rev Med Devices 2015;12:431–7.

PowersJH,PatrickDL,WaltonMK,MarquisP,CanoS,HobartJ,Isaac M, Vamvakas S, Slagle A, Molsen E, Burke LB. Clinician-reported outcome assessments of treatment benefit: report of the ISPOR clinical outcome assessment emerging good practices task force. Value Health 2017;20:2–14.

Ramsey SD, Willke RJ, Glick H, Reed SD, Augustovski F, Jonsson B, Briggs A, Sullivan SD. Cost-effectiveness analysis alongside clinical trials II-an ISPOR Good research practices task force report. Value Health 2015;18:161–72.

Ray D. Conclusions, reports, and summary of the Minneapolis pain seminar on electrical stimulation of the human nervous system for the control of pain. Surg Neurol 1975;4:202–4.

Rock AK, Truong H, Park YL, Pilitsis JG. Spinal cord stimulation. Neurosurg Clin N Am 2019;30:169–94.

RussoM,BrookerC,CousinsMJ,TaylorN,BoeselT,SullivanR,Holford L, Hanson E, Gmel GE, Shariati NH, Poree L, Parker J. Sustained long-term outcomes with closed-loop spinal cord stimulation: 12-month results of the prospective, multicenter, open-label avalon study. Neurosurgery 2020.

Russo M, Cousins MJ, Brooker C, Taylor N, Boesel T, Sullivan R, Poree L, Shariati NH, Hanson E, Parker J. Effective relief of pain and associated symptoms with closed-loop spinal cord stimulation system: preliminary results of the avalon study. Neuromodulation 2018;21:38–47.

Sadler ME, Yamamoto RT, Khurana L, Dallabrida SM. The impact of rater training on clinical out comes assessment data: aliterature review. Int J Clin Trials 2017;4:101–10.

Keller S, Correia H. The patient-reported outcome measurement information system (PROMIS®): international update. Available at: http://www.healthmeasures.net/images/PROMIS/pronl47_keller.pdf. Accessed January 5, 2018.

Sanders GD, Neumann PJ, Basu A, Brock DW, Feeny D, Krahn M, Kuntz KM, Meltzer DO, Owens DK, Prosser LA, Salomon JA, Sculpher MJ, Trikalinos TA, Russell LB, Siegel JE, Ganiats TG. Recommendations for conduct, methodological practices, and reporting of cost-effectiveness analyses: second panel on cost- effectiveness in health and medicine. JAMA 2016;316:1093–103.

Savovic ́ J, Jones H, Altman D, Harris R, Juni P, Pildal J, Als-Nielsen B, Balk E, Gluud C, Gluud L, Ioannidis J, Schulz K, Beynon R, Welton N, Wood L, Moher D, Deeks J, Sterne J. Influence of reported study design characteristics on intervention effect estimates from randomised controlled trials: combined analysis of meta-epidemiological studies. Health Technol Assess Winch Engl 2012;16:1–82.

Schulz KF, Chalmers I, Hayes RJ, Altman DG. Empirical evidence of bias. Dimensions of methodological quality associated with estimates of treatment effects in controlled trials. JAMA 1995;273:408–12.

Schwartz JL. Real-world evidence, public participation, and the FDA. Hastings Cent Rep 2017;47:7–8.

Senn SS.Cross-over trials clinical research. Hoboken, NJ: Wiley,2002.

Shealy CN, Mortimer JT, Reswick JB. Electrical inhibition of pain by stimulation of the dorsal columns: preliminary clinical report. Anesth Analg 1967;46:489–91.

ShiovitzTM,WilcoxCS,GevorgyanL,ShawkatA.CNSsitescooperate to detect duplicate subjects with a clinical trial subject registry. Innov Clin Neurosci 2013;10:17–21.

Shipley J, North RB. Chapter 55-a review of spinal cord stimulation cost studies. In: Krames ES, Peckham PH, Rezai AR, editors. Neuromodulation. 2nd ed. Cambridge, MA:Academic Press, 2018. p. 701–19. doi:10.1016/B978-0-12-805353-9.00055-3.

Smith SM, Amtmann D, Askew RL, Gewandter JS, Hunsinger M, Jensen MP, McDermott MP, Patel KV, Williams M, Bacci ED, Burke LB, Chambers CT, Cooper SA, Cowan P, Desjardins P, Etropolski M, Farrar JT, Gilron I, Huang I-zu, Katz M, Kerns RD, Kopecky EA, Rappaport BA, Resnick M, Strand V, Vanhove GF, Veasley C, Versavel M, Wasan AD, Turk DC, Dworkin RH. Pain intensity rating training: results from an exploratory study of the ACTTION PROTECCT system. PAIN 2016;157: 1056–64.

Smith SM, Wang AT, Katz NP, McDermott MP, Burke LB, Coplan P, Gilron I, Hertz SH, Lin AH, Rappaport BA, Rowbotham MC, Sampaio C, Sweeney M, Turk DC, Dworkin RH. Adverse event assessment, analysis, and reporting in recent published analgesic clinical trials: ACTTION systematic review and recommendations. PAIN 2013;154: 997–1008.

Stone AA, Shiffman S, Schwartz JE, Broderick JE, Hufford MR. Patient non-compliance with paper diaries. BMJ 2002;324:1193–4.

SullivanGM,FeinnR.Usingeffectsize-orwhythePvalueisnotenough. J Grad Med Educ 2012; 4:279–82.

Taylor RS, Taylor RJ, Van Buyten J-P, Buchser E, North R, Bayliss S. The cost effectiveness of spinal cord stimulation in the treatment of pain: a systematic review of the literature. J Pain Symptom Manage 2004;27: 370–8.

Tesfaye S, Watt J, Benbow SJ, Pang KA, Miles J, MacFarlane IA. Electrical spinal-cord stimulation for painful diabetic peripheral neuropathy. Lancet Lond Engl 1996;348:1698–701.

ThomsonSJ,TavakkolizadehM,Love-Jones S, Patel NK, Gu JW, Bains A, Doan Q, Moffitt M. Effects of rate on analgesia in kilohertz frequency spinal cord stimulation: results of the PROCO randomized controlled trial. Neuromodulation 2018;21:67–76.

Toth LP, Park S, Springer CM, Feyerabend MD, Steeves JA, Bassett DR. Video-recorded validation of wearable step counters under free- living conditions. Med Sci Sports Exerc 2018;50:1315–22.

Treister R, Eaton TA, Trudeau JJ, Elder H, Katz NP. Development and preliminary validation of the focussed analgesia selection test to identify accurate pain reporters. J Pain Res 2017; 10:319–26.

TreisterR,HonigmanL,LawalOD,LanierRK,KatzNP.Adeeperlookat pain variability and its relationship with the placebo response: results from a randomized, double-blind, placebo-controlled clinical trial of naproxen in osteoarthritis of the knee. PAIN 2019;160:1522–8.

Treister R, Lawal OD, Shecter JD, Khurana N, Bothmer J, Field M, Harte SE, Kruger GH, Katz NP. Accurate pain reporting training diminishes the placebo response: results from a randomised, double-blind, crossover trial. PLoS One 2018;13:e0197844.

Treister R, Suzan E, Lawal OD, Katz NP. Staircase-evoked pain may be more sensitive than traditional pain assessments in discriminating analgesic effects: a randomized, placebo-controlled trial of naproxen in patients with osteoarthritis of the knee. Clin J Pain 2019;35:50–5.

Treister R, Trudeau JJ, Van Inwegen R, Jones JK, Katz NP. Development and feasibility of the misuse, abuse, and diversion drug event reporting system (MADDERS®). Am J Addict 2016;25:641–51.

Trudeau J, Van Inwegen R, Eaton T, Bhat G, Paillard F, Ng D, Tan K, Katz NP. Assessment of pain and activity using an electronic pain diary and actigraphy device in a randomized, placebo-controlled crossover trial of celecoxib in osteoarthritis of the knee. Pain Pract 2015;15:247–55.

Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, Cleeland C, Dionne R, Farrar JT, Galer BS, Hewitt DJ, Jadad AR, Katz NP, Kramer LD, Manning DC, McCormick CG, McDermott MP, McGrath P, Quessy S, Rappaport BA, Robinson JP, Royal MA, Simon L, Stauffer JW, Stein W, Tollett J, Witter J. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. PAIN 2003; 106:337–45.

Turk DC, Dworkin RH, Revicki D, Harding G, Burke LB, Cella D, Cleeland CS, Cowan P, Farrar JT, Hertz S, Max MB, Rappaport BA. Identifying important outcome domains for chronic pain clinical trials: an IMMPACT survey of people with pain. PAIN 2008;137:276–85.

Turk DC, Fillingim RB, Ohrbach R, Patel KV. Assessment of psychosocial and functional impact of chronic pain. J Pain 2016;17:T21–49.

Turner JA, Loeser JD, Deyo RA, Sanders SB. Spinal cord stimulation for patients with failed back surgery syndrome or complex regional pain syndrome: a systematic review of effectiveness and complications. PAIN 2004;108:137–47.

Vase L, Wartolowska K. Pain, placebo, and test of treatment efficacy: a narrative review. Br J Anaesth 2019;123:e254–62.

Vetter TR, Mascha EJ. Bias, confounding, and interaction: lions and tigers, and bears, oh My. Anesth Analg 2017;125:1042–8.

Wall PD, Sweet WH. Temporary abolition of pain in man. Science 1967; 155:108–9.

Walton MK, Powers JH, Hobart J, Patrick D, Marquis P, Vamvakas S, Isaac M, Molsen E, Cano S, Burke LB. Clinical outcome assessments: conceptual foundation-report of the ISPOR clinical outcomes assessment-emerging Good practices for outcomes research task force. Value Health 2015;18:741–52.

Van der Wilt GJ, Zielhuis GA. Merging evidence-based and mechanism-based medicine. Lancet Lond Engl 2008;372:519–20.

Wise RA, Bartlett SJ, Brown ED, Castro M, Cohen R, Holbrook JT, Irvin CG, Rand CS, Sockrider MM, Sugar EA; American Lung Association Asthma Clinical Research Centers. Randomized trial of the effect of drug presentation on asthma outcomes: the American lung association asthma clinical research centers. J Allergy Clin Immunol 2009;124: 436–44, 444e1–8.

Zhang TC, Janik JJ, Grill WM. Mechanisms and models of spinal cord stimulation for the treatment of neuropathic pain. Brain Res 2014;1569: 19–31.

Zimbroff DL. Patient and rater education of expectations in clinical trials (PREECT). J Clin Psychopharmacol 2001;21:251–2.

Zipes DP, Svorkdal N, Berman D, Boortz-Marx R, Henry T, Lerman A, Ross E, Turner M, Irwin C. Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization. Neuromodulation 2012;15:550-8; discussion 558-559.