Malonne 2004.

Methods	Parallel, multicenter, double‐blind RCT
Participants	231 adults ages 45–80 years with OA of hip or knee diagnosis made with the European League Against Rheumatism criteria. Participants were included if they had a pain score ≥ 35 mm on 100‐mm Huskisson horizontal VAS scale (scale 0 = no pain to 100 = worst pain) and a functional discomfort score ≥ 4 on the Lequesne Functional Discomfort Index (total score 0 = absence of pain to 20 = most intense pain). % women: active group: 72.1%; control group: 73.1%
Interventions	14‐day treatment period. Active group: tramadol LP SR 200 mg/day Control group: placebo Concomitant treatment with acetaminophen as a rescue medication
Outcomes	PI evaluated with VAS Patient Global Assessment and use of rescue medication. Extracted pain outcome: Huskisson VAS for pain (0–100 mm) at 14 days, with lower values indicating benefit. Physical function data not extractable for purposes of this review.
Notes	Funding source not mentioned.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Quote: "Study drugs were allocated to patients based on a center randomization list." (p.1776) No mention as to how the randomization was carried out.
Allocation concealment (selection bias)	Unclear risk	No mention of allocation concealment.
Blinding of personnel	Unclear risk	Authors did not explicitly report blinding of personnel
Blinding of participants	Low risk	Quote: "Capsules of identical appearance containing either inactive ingredients or tramadol LP 200 mg were prepared and dispensed in blister packs." (p.1776)
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Since this was a participant‐reported outcome and participants were blinded, the outcome assessment was considered blinded.
Incomplete outcome data for pain and physical function	Low risk	Quote: "Two hundred thirty‐one patients were randomized to treatment, and 230 (…) were evaluable for efficacy and safety." (p.1776) Quote: "A separate analysis was conducted in the patients who did not take rescue medication." Quote: "92 patients were included in the assessment of those who did not take rescue medication." (p.1776) 230/231 analyzable participants used in safety analysis but only 197 completed treatment and were used in the benefits analysis. The missing 33 participants were omitted due to no VAS at day 14. Total withdrawals: 23.4% with tramadol vs 5.9% with placebo. Withdrawals due to adverse events: 21.6% with tramadol vs 1.7% with placebo.
Incomplete outcome data for adverse effects All outcomes	Low risk	Quote: "Two hundred thirty‐one patients were randomized to treatment, and 230 (…) were evaluable for efficacy and safety." (p.1776) Quote: "A separate analysis was conducted in the patients who did not take rescue medication." Quote: "92 patients were included in the assessment of those who did not take rescue medication." (p.1776) 230/231 analyzable participants used in safety analysis but only 197 completed treatment and were used in the benefits analysis. The missing 33 participants were omitted due to no VAS at day 14. Total withdrawals: 23.4% with tramadol vs 5.9% with placebo. Withdrawals due to adverse events: 21.6% with tramadol vs 1.7% with placebo.
Selective reporting (reporting bias)	Unclear risk	All prespecified outcomes (global pain score, Lequesne Functional Discomfort Index, safety/adverse events) appeared to have been reported in the results, but we did not have access to the protocols for verification.
Other biases	Low risk	No other sources of bias.