379: Blinding Assessment Practices in Pharmacotherapy & Neuromodulation RCTs for Neuropathic Pain

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Neuropathic pain , Pharmacological treatments, Neuromodulation (e.g. TMS, TDCS, FUS, SCS, MCS, DBS, vagus nerve stimulation)

Background and Aims: In randomized controlled trials (RCTs), study participants and research personnel are often blinded to minimize bias related to knowing treatment allocation [1]. To determine if blinding was effective, participants and research personnel may be asked at the end of the study which treatment they believe they received (“treatment guess”). We conducted a descriptive review which aimed to characterize blinding assessment (BA) and its reporting in pharmacotherapy and neuromodulation neuropathic pain RCTs.

Methods: This is a secondary analysis of a recently completed update [2] to a 2015 systematic review and meta-analysis [3], by the IASP Neuropathic Pain Study Interest Group (NeuPSIG), with methods previously described. We included 288 double-blind, randomized, placebo-controlled trials lasting at least 3 weeks with at least 10 participants per group that examined pharmacotherapy or non-invasive neuromodulation for use in neuropathic pain, published up to February 12, 2024.

Results: Of 288 studies, 37 (12.5%) reported a BA. Of these studies, 19 were crossover, 17 parallel, and 1 partial crossover in design. Most were single site studies (57%) and received non-industry funding (68%). 27% included an ‘unsure’ answer option for participants’ treatment guess, and 38% asked the reason for the treatment guess. There were no clear trends in BA reporting across time nor based on treatment type. 15/37 studies provided sufficient data to calculate Bang’s Blinding Index (BI) to determine blinding success. Blinding was effective (BI=0 ±0.2) in 10/15 placebo and 10/15 treatment arms, suggesting that participants guessed no better than chance. 6 placebo and 5 treatment arms trended towards unblinding (BI>0.2), whereas 1 placebo and 2 treatment arms trended towards misinformed guessing (BI<-0.2).

Conclusions: Overall, our findings suggest that BA is done in a minority of neuropathic pain trials, and with variable methodology. Given the importance of minimizing risk of bias due to treatment unblinding, further research and consensus building is necessary to determine if and/or how BA should be conducted and interpreted in analgesic clinical trials.

References: [1] Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H-Y, Corbett MS, Eldridge SM. RoB 2: a revised tool for assessing risk of bias in randomised trials. bmj 2019;366.
[2] Soliman N, Moisset X, Ferraro MC, de Andrade DC, Baron R, Belton J, Bennett DLH, Calvo M, Dougherty P, Gilron I, Hietaharju AJ, Hosomi K, Kamerman PR, Kemp H, Enax-Krumova EK, McNicol E, Price TJ, Raja SN, Rice ASC, Smith BH, Talkington F, Truini A, Vollert J, Attal N, Finnerup NB, Haroutounian S; NeuPSIG Review Update Study Group. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. The Lancet Neurology 2025;24(5):413–428.
[3] Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, Gilron I, Haanpää M, Hansson P, Jensen TS, Kamerman PR, Lund K, Moore A, Raja SN, Rice AS, Rowbotham M, Sena E, Siddall P, Smith BH, Wallace M. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet Neurology 2015;14(2):162-73.

Presenting Author: Landon T. Montag
Submitting Author: Landon Montag

Senior Author: Ian Gilron

IASP 2026 Global Year theme of Neuropathic Pain: Yes

• Landon T. Montag - School of Medicine, Queen's University, Kingston, Canada.
• Nadia Soliman - Pain Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
• Xavier Moisset - Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol, Clermont-Ferrand, France.
• Michael C. Ferraro - Centre for Pain IMPACT, Neuroscience Research Australia, Australia; Faculty of Medicine and Health, University of New South Wales Sydney, NSW, Australia.
• Daniel Ciampi de Andrade - Center for Neuroplasticity and Pain, Health Science and Technology Department, Faculty of Medicine, Aalborg University, Denmark.
• Ralf Baron - Division of Neurological Pain Research and Therapy, Department of Neurology, Christian-Albrechts-University, Kiel, Germany.
• Joletta Belton - Independent Patient Partner, Fraser, CO, USA.
• David L. H. Bennett - The Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, UK.
• Margarita Calvo - Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile; Anesthesiology Division, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
• Patrick M. Dougherty - Department of Pain Medicine, MD Anderson Cancer Center, Houston, TX, USA.
• Aki J. Hietaharju - Department of Neurology, Tampere University Hospital, Tampere, Finland.
• Koichi Hosomi - Department of Neurosurgery, The University of Osaka Graduate School of Medicine, Suita, Japan.
• Peter R. Kamerman - Brain Function Research Group, Department of Physiology, School of Biomedical Sciences, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
• Harriet Kemp - Pain Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
• Elena K. Enax-Krumova - Ruhr University Bochum, BG University Hospital Bergmannsheil, Department of Neurology, Germany.
• Ewan McNicol - Department of Pharmacy Practice, Massachusetts College of Pharmacy and Health Sciences, Boston, MA, USA.
• Theodore J. Price - Center for Advanced Pain Studies, Richardson, TX, USA; Department of Neuroscience, University of Texas at Dallas, School of Behavioral and Brain Sciences, Richardson, TX, USA.
• Srinivasa N. Raja - Departments of Anesthesiology and Critical Care Medicine and Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
• Andrew S. C. Rice - Pain Research Group, Department of Surgery and Cancer, Imperial College London, London, UK.
• Blair H. Smith - Division of Population Health and Genomics, School of Medicine, University of Dundee, Dundee, UK.
• Fiona Talkington - Broadcaster (BBC), writer, and patient advocate, Reading, UK.
• Andrea Truini - Department of Human Neuroscience, Sapienza University, Rome, Italy.
• Jan Vollert - Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter, UK.
• Nadine Attal - Inserm U987, APHP, UVSQ Paris Saclay University, Hôpital Ambroise Paré, Boulogne-Billancourt, France.
• Nanna B. Finnerup - Danish Pain Research Center, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
• Simon Haroutounian - Department of Anesthesiology, Washington University in St Louis School of Medicine, St Louis, MO, USA.
• Luana Colloca - Department of Pain and Translational Symptom Science, Placebo Beyond Opinions Center, School of Nursing, University of Maryland, Maryland, USA.
• Lene Vase - Department of Psychology and Behavioural Sciences, Aarhus University, Aarhus, Denmark.
• Tim V. Salomons - Centre for Neuroscience Studies, Queen’s University, Kingston, Canada; Department of Psychology, Queen’s University, Kingston, Canada.
• Bethany Gwyther - Royal Free Hospital, London, NHS England.
• David Hohenschurz-Schmidt - Imperial Clinical Trials Unit, School of Public Health, Imperial College London, London, UK.
• Jules Phalip - Université Clermont Auvergne, CHU Clermont-Ferrand, Inserm, Neuro-Dol, Clermont-Ferrand, France; Fondation ANALGESIA, Faculté de médecine, 63000 Clermont-Ferrand, France.
• Tjokorda Istri Pramitasuri - Department of Neurology, Faculty of Medicine, Universitas Udayana, Bali, Indonesia.
• Nina Taule-Lim - Siriraj Hospital, Bangkok, Thailand.
• Quyen V. Than - Department of Anesthesiology, Hospital 199, Da Nang, Vietnam.
• Jan D. Wandrey - Department of Anaesthesiology and Intensive Care, Campus Charité Mitte and Campus Virchow-Klinikum, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Germany; BIH Charité Digital Clinician Scientist Program, Berlin Institute of Health at Charité – Universitätsmedizin Berlin, BIH Biomedical Innovation Academy, Berlin, Germany.
• Md Zunaid - Bangladesh Civil Service (Health Cadre), Ministry of Health and Family Welfare, Bangladesh.
• Ian Gilron - Department of Anesthesiology and Perioperative Medicine, Queen's University, Kingston, ON, Canada; Biomedical & Molecular Sciences, Queen's University, Kingston, ON, Canada; Centre for Neuroscience Studies, Queen's University, Kingston, ON, Canada; School of Policy Studies, Queen's University, Kingston, ON, Canada; Kingston Health Sciences Centre, Providence Care Hospital, Kingston, ON, Canada.