Avery 2013

Methods	Parallel RCT
Participants	Country of study: USA Setting: unclear Condition: chronic widespread pain Prior management details: not reported n = 19 Age mean (SD): active 54.86 (7.65) years, sham 52.09 (10.02) years Duration of symptoms (months mean (SD)): active group 11 (4.26), sham group 15.64 (6.93) Gender distribution: all F
Interventions	Stimulation type: rTMS Stimulation parameters: frequency 10 Hz; coil orientation not specified; 120% RMT; number of trains 75; duration of trains 4 s; ITI 26 s; total number of pulses 3000 Stimulation location: L DLPFC Number of treatments: 15 sessions over 4 weeks Control type: sham coil ‐ controls for visual, auditory and scalp sensory cues
Outcomes	Primary: pain NRS 0‐10 anchors not reported When taken: end of treatment period, 1 month following and 3 months following Secondary: pain interference BPI QoL SF‐36 AEs: multiple minor; no clear difference in incidence between active and sham stimulation
Notes	Government‐funded study, manufacturer loaned stimulators COI: funded by the National Institute for Arthritis, Musculoskeletal and Skin Diseases, R21 ART053963 and the Bipolar Illness Fund Neuronetics, Inc. loaned the TMS machine to the study Dr. Avery was a consultant for Neuronetics, Inc. for one day, is a member of the Data and Safety Monitoring Board for Cerval Neuortech, Inc., was on the speakers bureau for Eli Lilly and Takeda, was a consultant for Takeda and received a grant from the National Institute of Mental Health. Dr. Roy‐Byrne is editor for Journal Watch, Depression and Anxiety, and UpToDate and has stock in Valant Medical Systems. None of the other authors has potential COI.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "At the completion of the baseline assessment, patients were randomly assigned to either real TMS or sham stimulation using a computerized randomization program that uses an adaptive randomization and stratification strategy."
Allocation concealment (selection bias)	Unclear risk	Quote: "Based on the randomization, a "smart card" which determined whether the real TMS or sham coil would be administered was assigned to a particular patient. The card had only a code number that did not reveal the randomization." "The research coordinator blind to the randomization repeated the baseline assessments" Comment: not entirely clear whether the personnel overseeing randomisation was separate from that performing the screening assessment.
Adequate blinding of participants?	Low risk	Quote: "... sham stimulation with the electromagnet blocked within the coil by a piece of metal so the cortex was not stimulated. The coils appeared identical. Electrodes were attached to the left side of the forehead for each subject for each session. Those receiving the sham stimulation received an electrical stimulus to the forehead during the sham stimulation. Those receiving the real TMS received no electrical stimulation to the electrodes. Both groups experienced a sensation in the area of the left forehead. In addition, all subjects were given special earplugs and received an audible noise during the stimulation to mask any possible sound differences between the TMS and sham conditions." Comment: optimal sham ‐ controls for visual, sensory and auditory cues Formal testing ‐ blinding appears robust
Adequate blinding of assessors?	Low risk	Quote: "The research coordinator blind to the randomization repeated the baseline assessments of pain, functional status, depression, fatigue, and sleep before the 1st and after the 5th, the 10th, and the 15th TMS sessions as well as 1 week, 1 month, and 3 months after the last TMS treatment except for the SF‐36, neuropsychological tests, audiometry and the dolorimetry which were only done at baseline and one week after the 15th TMS session." Comment: while TMS physicians guessed beyond chance the raters were separate from this process
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quote: "To examine differences in changes in outcomes over time between TMS and comparison group subjects, we estimated random coefficient models following the intent‐to‐treat principle." "11 were randomized to the sham group and 8 were randomized to the TMS group. However, one subject randomized to the TMS had a baseline BIRS score of 4 which was well below the BIRS score of 8 required for randomization. Because of this incorrect randomization, this subject was excluded from the efficacy analyses, but was included in the analysis of side effects. The clinical characteristics of those correctly randomized are in Table 1. One subject in the TMS dropped out after the 10th session because of lack of response and is included in the analyses." Comment: of 2 dropouts from the TMS group, 1 was excluded (reasons given)
Selective reporting (reporting bias)	Low risk	Comment: all outcomes presented in full in study report
Study Size	High risk	Comment: < 50 participants per treatment arm
Study duration	Low risk	Comment: > 8 weeks' follow‐up
Other bias	Low risk	No other bias detected