Arnold 2012b.

Study characteristics
Methods	Design: parallel Duration: 14 weeks Assessment: baseline and post‐intervention Country: USA and Canada
Participants	Pain condition: fibromyalgia Population: adults with fibromyalgia Minimum pain intensity: ≥ 40 out of 100 Inclusion criteria People aged ≥ 18 who met the ACR 1990 criteria for primary fibromyalgia Score of ≥ 40 mm on 100 mm VAS for pain intensity Exclusion criteria Comorbid physical and mental health conditions excluded Total participants randomised: 1122 Age in years (mean, range): 50 (19‐84) Gender: 1009/1122 were female Pain duration in years (mean, range): 7 (0‐55)
Interventions	Esreboxetine 4 mg n = 245 SNRI Fixed dose Esreboxetine 8 mg n = 254 SNRI Fixed dose Esreboxetine 10 mg n = 255 SNRI Fixed dose Placebo n = 255 Identical appearance Inert
Outcomes	Pain intensity Physical function Mood Quality of life Moderate pain relief Substantial pain relife PGIC AEs SAEs Withdrawal
Missing data methods	LOCF with BOCF as a sensitivity analysis on pain outcomes
Funding source	Pharmaceutical ‐ Pfizer
Conflicts of interest	Dr Arnold has received consulting fees from Eli Lilly, Cypress Bioscience, Forest Laboratories, Takeda, AstraZeneca, Sanofi‐Aventis, Grunenthal, Johnson & Johnson, and Daiichi Sankyo (less than USD 10,000 each) and from Pfizer (> USD 10,000); she has received research grants from Eli Lilly, Pfizer, Cypress Bioscience, Boehringer Ingelheim, Forest Laboratories, Novartis, and Takeda. Dr Hirsch owns stock or stock options in AstraZeneca. Dr Sanders owns stock or stock options in Pfizer and AstraZeneca. Drs Ellis and Hughes own stock or stock options in Pfizer.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Eligible patients were then randomised, according to a computer‐generated pseudorandom code, in a 1:1:1:1 ratio
Allocation concealment (selection bias)	Low risk	A centralised telerandomisation system was used to manage the allocation of treatment
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Patients received esreboxetine or matching placebo once daily in the form of round, light grey tablets; all of the tablets were identical in appearance, to preserve blinding.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Self‐reported outcomes from blinded participants
Incomplete outcome data (attrition bias) All outcomes	High risk	High dropout across arms and significant differences in rates between placebo and intervention arms Attrition: Total: 406/1122 (36.2%) Placebo: 76/278 (27.3%) Esreboxetine 4 mg: 103/277 (37.2%) Esreboxetine 8 mg: 111/284 (39.1%) Esreboxetine 10 mg: 108/283 (38.2%)
Selective reporting (reporting bias)	High risk	Primary outcomes were switched on the trial registry. Protocol states they will collect and report HADS, SDI, and Sleep Interference but not published
Other bias	Low risk	No other sources of bias were identified.