Karlsson 2009.

Methods	Randomized, open‐label, controlled, parallel‐group non‐inferiority study
Participants	Participants ages > 18 years with clinical diagnosis of OA of the hip or knee (or both), based on ACR and radiographic criteria. % women: active group: 59.4%; control group: 53.8%
Interventions	Active group 1: tramadol pills (75, 100, 150 and 200 mg) titrated as needed to achieve stable pain control over 12 weeks Active group 2: 7‐day buprenorphine patches (5, 10 and 20 μg/hour)
Outcomes	PI: mean weekly BS‐11 pain score, calculated from the scores recorded in the participant diaries every evening. Global assessment of pain relief obtained by asking participants and investigators to rate the study medication in terms of pain relief (very poor, poor, fair, good or very good). Investigators assessed participants' pain, stiffness and ability to perform daily activities using WOMAC Other: participant‐recorded number of acetaminophen pills (rescue medication) taken daily. Sleep disturbance and quality of sleep assessed by asking participants the following questions: "How many nights have you woken due to pain in the past 7 nights?" and "Please rate the quality of sleep over the past 7 nights" (response options: very poor, poor, fair, good and very good). Participants' quality of life using the EuroQol EQ‐5D Health Status Index and EQ‐VAS. Adverse events reported. At visits 2 and 8, physical exam performed, and systolic and diastolic blood pressure and heart rate measured. Extracted pain outcome: scores on 11‐point box scale at 12 weeks, with lower values indicating benefit Physical function outcomes not reported
Notes	Sponsored and designed by Mundipharma AB, Goteborg, Sweden
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote: "a computer‐generated randomization schedule was used to allocate patients." (p.505) Quote: "Patients were randomized in a 1:1 ratio." (p.503) Quote: "Eligible patients were randomized to the lowest available patient number at their site." (p.506)
Allocation concealment (selection bias)	Unclear risk	Quote: "Sealed envelopes with the treatment codes were forwarded to investigators at each site." (p.506) Insufficient information about allocation concealment.
Blinding of personnel	High risk	Quote: "When the study was designed, it was felt that the potential benefits of an open‐label design outweighed those of a blinded design." (p.511)
Blinding of participants	High risk	Quote: "When the study was designed, it was felt that the potential benefits of an open‐label design outweighed those of a blinded design." (p.511)
Blinding of outcome assessment (detection bias) All outcomes	High risk	Quote: "When the study was designed, it was felt that the potential benefits of an open‐label design outweighed those of a blinded design." (p.511)
Incomplete outcome data for pain and physical function	High risk	Quote: "The full analysis set (FAS) included all patients who were randomized and received at least 1 dose of study medication. The per‐protocol analysis set (PPAS) included patients who were in the FAS and had no major protocol violations." (p.507) The FAS did not include all randomized participants who completed the treatment. 20/69 (28.9%) participants in the patches group were not included in FAS. 25/66 (37.8%) participants in the tramadol group were not included in the FAS. Withdrawals due to adverse events: 28.8% with tramadol vs 14.5% with patches. Total withdrawals: 31.8% with tramadol vs 20.3% with patches.
Incomplete outcome data for adverse effects All outcomes	Low risk	Quote: "The full analysis set (FAS) included all patients who were randomized and received at least 1 dose of study medication. The per‐protocol analysis set (PPAS) included patients who were in the FAS and had no major protocol violations." (p.507) The per‐protocol analysis set does not include all randomized participants who completed the treatment. 20/69 (28.9%) participants in the patches group were not included in FAS. 25/66 (37.8%) participants in the tramadol group were not included in the FAS. Withdrawals due to adverse events: 28.8% with tramadol vs 14.5% with patches. Total withdrawals: 31.8% with tramadol vs 20.3% with patches.
Selective reporting (reporting bias)	Low risk	Quote: "There were changes from baseline to study completion on all WOMAC Osteoarthritis Index subscale scores in both treatment groups, with no significant differences between treatment groups." (p.508) WOMAC Osteoarthritis Index subscale scores not reported but stated to have no significant differences between treatments.
Other biases	Low risk	No other sources of bias.