Summary of findings 7. Tramadol in combination with acetaminophen compared with other opioids for osteoarthritis.

Tramadol in combination with acetaminophen compared with other opioids for osteoarthritis
Patient or population: osteoarthritis Settings: outpatient clinics Intervention: tramadol in combination with acetaminophen Comparison: other opioids
Outcomesa	Illustrative comparative risks* (95% CI)		Relative effect (95% CI)	No of participants (studies)	Quality of the evidence (GRADE)	Comments
	Assumed risk**	Corresponding risk**
	Other opioids	Tramadol in combination with acetaminophen
Pain assessed with: self‐report VAS pain intensity (scale 0 to 10 mm where 0 = no pain) Follow‐up: 12 weeks	The mean pain was 6.4 points	The mean pain of the intervention group was 0.3 points higher (1.8 higher to 1.3 lower)b	—	130 (1 RCT)	⊕⊕⊝⊝ Lowe,f	Mean pain: 3% absolute worsening (95% CI 18% worsening to 13% improvement),b 5% relative worsening (95% CI 28% worsening to 20% improvement),f SMD 0.06 (95% CI –0.31, 0.43), NNTB not applicableh
	32 out of 100 improved by 20%c	2 less out of 100 (16 less to 13 more) in the intervention group improved by 20%c	RR 0.96 (95% CI 0.67 to 1.27)d
Physical function	—	—	—	—	—	Not reported
Number of participants experiencing any adverse event	—	—	—	—	—	Not reported
Number of participants who withdrew due to adverse events	—	—	—	—	—	Not reported
Number of participants experiencing any serious adverse events	—	—	—	—	—	Not reported
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). **The assumed and the corresponded risk was calculated from the SMD and SE. CI: confidence interval; MCID: minimal clinically important difference; NNTB: number needed to treat for an additional beneficial outcome; RR: risk ratio;SD: standard deviation; SE: standard error; SMD: standardized mean difference.
GRADE Working Group grades of evidence High quality: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

^aContinuous outcomes summarized using SMD and SE, and binary outcomes expressed as RR. We used standard inverse‐variance fixed‐effect meta‐analysis to combine the trials in Review Manager 5 (Review Manager 2014).
 ^bAbsolute effect on a common scale (e.g. 100‐mm, 1700‐point scale) calculated by multiplying the SMD by the SD of the scale (in the control group at baseline) as suggested by the Cochrane Handbook for Systematic Reviews of Interventions (Section 12.6.4; Higgins 2011).
 ^cAssumed and corresponding risks calculated from the SMD and SE, with improvement based on an MCID of 20% of the given scale using the Wells calculator (from the Cochrane Musculoskeletal Group Editorial office; musculoskeletal.cochrane.org/).
 ^dRR and its 95% CI calculated using the assumed risk of the control group and corresponding risk of the treatment group. Corresponding risk was divided by the assumed risk.
 ^eDowngraded one level for unclear risk of bias (all trials had high or unclear risk of at least one type of bias).
 ^fDowngraded one level for imprecision.
 ^gRelative improvement percentage is defined as relative to the control group risk at baseline.
 ^hNNTB corresponded to the number of participants that needed to be treated to see one participant improve. Improvement defined as reaching an MCID of 20% on the given scale. NNTB calculated using the Wells calculator (from the Cochrane Musculoskeletal Group Editorial office; musculoskeletal.cochrane.org/ne.org/). It was only calculated for statistically significant results.