Chappell 2011.

Study characteristics
Methods	Design: parallel Duration: 13 weeks Assessment: baseline and post‐intervention Country: USA, Canada, Greece, Russia, Sweden
Participants	Pain condition: knee OA Population: adults aged ≥ 40 with knee OA Minimum pain intensity: ≥ 4 on 0‐10 VAS Inclusion criteria Adults aged ≥ 40 with knee OA matching ACR criteria Pain ≥ 14 days a month for 3 months prior to study entry Mean score of ≥ on 24‐h average pain score (0‐10) on first 2 study visits Exclusion criteria Comorbid physical and mental health conditions Total participants randomised: 256 Age in years (mean): 62.5 Gender: 196/256 were female Pain duration in years (mean): 7.4
Interventions	Placebo n = 128 Inert Matched dosing Duloxetine n = 128 SNRI Fixed dose of 60 mg for 6 weeks, then titrated to fixed dosage of 120 mg for weeks 7‐13 dependent on 30% pain relief
Outcomes	Pain intensity Physical function Moderate pain relief Substantial pain relief PGIC AEs SAEs Withdrawal
Missing data methods	ITT with LOCF, sensitivity analysis of primary outcome with BOCF and modified‐BOCF
Funding source	Pharmaceutical ‐ Eli Lilly
Conflicts of interest	This study was sponsored by Eli Lilly and Company, Indianapolis, IN, USA. Drs Chappell, Skljarevski, Desaiah, Liu‐Seifert, and Ms Zhang are employees and stockholders of Eli Lilly and Company. Drs Belenkov and Brown were participating investigators in the conduct of this study and received funding from Eli Lilly and Company.
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Assignment to treatment was determined by a computer‐generated random sequence
Allocation concealment (selection bias)	Low risk	Participants were allocated using an interactive voice response system to ensure blinding.
Blinding of participants and personnel (performance bias) All outcomes	Unclear risk	States double‐blind and matched dosing, but don't mention drug appearance
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Self‐reported outcomes from participants, but unsure of blinding procedures
Incomplete outcome data (attrition bias) All outcomes	High risk	Attrition rates may be influenced by group allocation: "Significantly more patients in the duloxetine group (n = 24, 18.8%) discontinued from the study due to adverse events (P = 0.002) than patients in the placebo group (n = 7, 5.5%)." Used LOCF, BOCF, mBOCF, ITT to handle/impute missing data Attrition Total: Placebo: 17/128 (13.3%) Duloxetine 60‐120 mg: 35/128 (27.3%)
Selective reporting (reporting bias)	High risk	Data not presented on outcomes that were non‐significant
Other bias	Low risk	No other sources of bias were identified.