Bird 1995.

Methods	Cross‐over, double‐blind RCT Setting: clinic
Participants	40 participants with radiologically confirmed diagnosis of OA of hip or knee within 12 months of starting the study; 19 participants completed both treatment periods. % women: active group: 65%; control group: 70% Active group: 13 participants had moderate to severe OA; control group: 14 participants had moderate to severe OA
Interventions	Cross‐over trial Initial visit: active group received tramadol 50 mg 4 times/day; control group received pentazocine 50 mg 4 times/day) for 2‐week period. Second visit: participants crossed over to the other drug for another 2 weeks. No washout period
Outcomes	Major: Pain severity (4‐point Likert scale: none, mild, moderate, severe) recorded on diary cards completed daily Duration of morning stiffness (minutes) and severity (same 4‐point Likert scale) Number of acetaminophen tablets consumed Minor: Duration of inactivity stiffness (minutes) Pain during daily activities and walking (none, mild, moderate, severe) Pain during sleep (normal sleep, some interruption of sleep, moderate interruption of sleep, no sleep) Functional impairment, e.g. climbing stairs, getting out of bed and rising from a chair (no difficulty, a little difficulty, moderate difficulty, great difficulty or impossible) Participant's assessment of treatment (very good, good, fair, poor or very poor) Extracted pain outcome: severity of pain (4‐point Likert scale) during the last 7 days of treatment, with lower values indicating benefit Extracted physical function outcome: no extractable data
Notes	Grünenthal GmbH supplied the drugs
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"Patients were then randomly allocated to either tramadol 50 mg qds or pentazocine 50 mg qds." (p.182) No mention of how the allocation sequence was randomly generated.
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	Unclear risk	Authors did not explicitly report blinding of participants
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Authors did not explicitly report blinding of outcome assessors
Incomplete outcome data for pain and physical function	Unclear risk	Quote: "analyses of these total scores were (…) carried out on two patient cohorts. Cohort 1 comprised those patients who took at least one dose of the study medication in each period and who had pain scores for at least four days. Cohort 2 comprised patients who took at least one dose of study medication in each period and recorded pain scores on less than four days unless they withdrew due to lack of efficacy." (p.183) Quote: "The single patient withdrawing for treatment failure was taking pentazocine and experienced a flare in OA." (p.184) Quote: "the study was somewhat compromised by a high withdrawal rate due to adverse events." (p.187) Only 19/40 (47.5%) participants completed the study. Total withdrawals: 45% with tramadol vs 60% with pentazocine. Percentage for withdrawals due to adverse events: 45% with tramadol vs 55% with pentazocine. In cohort 2, unknown how many people withdrew due to lack of benefits so it is unknown how many participants were excluded from the analyses. Unknown how many people were in each cohort.
Incomplete outcome data for adverse effects All outcomes	Unclear risk	Quote: "analyses of these total scores were (…) carried out on two patient cohorts. Cohort 1 comprised those patients who took at least one dose of the study medication in each period and who had pain scores for at least four days. Cohort 2 comprised patients who took at least one dose of study medication in each period and recorded pain scores on less than four days unless they withdrew due to lack of efficacy." (p.183) Quote: "The single patient withdrawing for treatment failure was taking pentazocine and experienced a flare in OA." (p.184) Quote: "the study was somewhat compromised by a high withdrawal rate due to adverse events." (p.187) Only 19/40 (47.5%) participants completed the study. Total withdrawals: 45% with tramadol vs 60% with pentazocine. Percentage of withdrawals due to adverse events: 45% with tramadol vs 55% with pentazocine. In cohort 2, unknown how many people withdrew due to lack of benefits so it is unknown how many participants were excluded from the analyses. Unknown how many people were in each cohort.
Selective reporting (reporting bias)	Unclear risk	All prespecified outcomes (pain, stiffness, sleep quality, and physical function) appeared to have been reported in the results but we did not have access to the protocol for verification.
Other biases	High risk	4/18 (22%) participants in the pentazocine group used ≥ 80% of their medication but 13/19 (68.4%) participants in the tramadol group used ≥ 80% of their medication. Results on treatment benefits may have been biased because participants in the pentazocine group were not as compliant with taking their medication. Was use of a cross‐over design appropriate? Yes, OA was stable. Was it clear that the order of receiving treatments was randomized? Unclear, randomized but no details on randomization procedure. Can it be assumed that the trial was not biased from carry‐over effects? No, no washout period. Are unbiased data available? No, used a Wilcoxon Rank Sum test which is used for independent, not dependent samples.