Assessment of blinding in pharmacotherapy and noninvasive neuromodulation randomized controlled trials for neuropathic pain in adults

TY - JOUR

T1 - Assessment of blinding in pharmacotherapy and noninvasive neuromodulation randomized controlled trials for neuropathic pain in adults

AU - Montag, Landon T

AU - Soliman, Nadia

AU - Moisset, Xavier

AU - Ferraro, Michael C

AU - Ciampi de Andrade, Daniel

AU - Baron, Ralf

AU - Belton, Joletta

AU - Bennett, David L H

AU - Calvo, Margarita

AU - Dougherty, Patrick M

AU - Hietaharju, Aki J

AU - Hosomi, Koichi

AU - Kamerman, Peter R

AU - Kemp, Harriet

AU - Enax-Krumova, Elena K

AU - McNicol, Ewan

AU - Price, Theodore J

AU - Raja, Srinivasa N

AU - Rice, Andrew S C

AU - Smith, Blair H

AU - Talkington, Fiona

AU - Truini, Andrea

AU - Vollert, Jan

AU - Attal, Nadine

AU - Finnerup, Nanna B

AU - Haroutounian, Simon

AU - Colloca, Luana

AU - Vase, Lene

AU - Salomons, Tim V

AU - Gwyther, Bethany

AU - Hohenschurz-Schmidt, David

AU - Phalip, Jules

AU - Istri Pramitasuri, Tjokorda

AU - Taule-Lim, Nina

AU - Than, Quyen V

AU - Wandrey, Jan D

AU - Zunaid, Md

AU - Gilron, Ian

N1 - Copyright © 2026 International Association for the Study of Pain.

PY - 2026/9/11

Y1 - 2026/9/11

N2 - In randomized controlled trials (RCTs), study participants and research personnel are often blinded to minimize biases related to knowing treatment allocation. To determine if blinding was effective, participants may be asked which treatment they believe they received ("treatment guess"). This descriptive review characterized blinding assessment (BA) reporting in pharmacotherapy and neuromodulation neuropathic pain RCTs. Of 288 papers, 36 (12.5%) reported a BA. One paper reported the results of 2 studies, so in total 37 studies with a BA were assessed. Of these, 19 were crossover, 17 parallel, and 1 partial crossover in design. All 37 studies assessed participant blinding, and 10 also assessed investigator blinding. Approximately 27% included an "unsure" answer option for treatment guess, and 38% asked the reason for the guess. There were no clear patterns in BA reporting across time nor based on treatment type. Seventeen trials provided sufficient data to calculate Bang Blinding Index (BI) to determine blinding success. Participants remained blinded (BI = 0 ± 0.2) in 10/17 placebo and 10/17 treatment arms, 6 placebo and 5 treatment arms had a BI > 0.2 suggesting possible unblinding, whereas 1 placebo and 2 treatment arms had a BI < -0.2 suggesting misinformed guessing. Overall, we found that BAs are done in a minority of published neuropathic pain trials and with variable methodology. Given the importance of minimizing risk of bias because of treatment unblinding, future studies should consider including BAs, and further consensus building is necessary to determine if and how BAs should be conducted and interpreted in analgesic clinical trials.

AB - In randomized controlled trials (RCTs), study participants and research personnel are often blinded to minimize biases related to knowing treatment allocation. To determine if blinding was effective, participants may be asked which treatment they believe they received ("treatment guess"). This descriptive review characterized blinding assessment (BA) reporting in pharmacotherapy and neuromodulation neuropathic pain RCTs. Of 288 papers, 36 (12.5%) reported a BA. One paper reported the results of 2 studies, so in total 37 studies with a BA were assessed. Of these, 19 were crossover, 17 parallel, and 1 partial crossover in design. All 37 studies assessed participant blinding, and 10 also assessed investigator blinding. Approximately 27% included an "unsure" answer option for treatment guess, and 38% asked the reason for the guess. There were no clear patterns in BA reporting across time nor based on treatment type. Seventeen trials provided sufficient data to calculate Bang Blinding Index (BI) to determine blinding success. Participants remained blinded (BI = 0 ± 0.2) in 10/17 placebo and 10/17 treatment arms, 6 placebo and 5 treatment arms had a BI > 0.2 suggesting possible unblinding, whereas 1 placebo and 2 treatment arms had a BI < -0.2 suggesting misinformed guessing. Overall, we found that BAs are done in a minority of published neuropathic pain trials and with variable methodology. Given the importance of minimizing risk of bias because of treatment unblinding, future studies should consider including BAs, and further consensus building is necessary to determine if and how BAs should be conducted and interpreted in analgesic clinical trials.

KW - Neuropathic pain

KW - Pharmacotherapy

KW - Neuromodulation

KW - Evidence-based

KW - Recommendations

KW - Blinding

KW - Masking

KW - Clinical trials

KW - Bias

U2 - 10.1097/j.pain.0000000000004120

DO - 10.1097/j.pain.0000000000004120

M3 - Article

C2 - 42751722

SN - 0304-3959

JO - Pain

JF - Pain

ER -