Summary of findings for the main comparison. Tramadol alone compared with placebo for osteoarthritis.
| Tramadol alone compared with placebo for osteoarthritis | ||||||
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Patient or population: osteoarthritis of the hip or knee, or both Settings: outpatient clinics Intervention: tramadol alone Comparison: placebo | ||||||
| Outcomesa | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk** | Corresponding risk** | |||||
| Placebo | Tramadol alone | |||||
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Pain assessed with: 0–100‐mm VAS pain intensity where 0 = no pain Follow‐up: range 1 week to 3 months |
The mean pain was 54.3 points | The mean pain in the intervention group was 4 points lower (3 lower to 5 lower)b | — | 3972 (8 RCTs) | ⊕⊕⊕⊝ Moderatee | Mean pain: 4% absolute improvement (95% CI 3% to 5% improvement),b 7% relative improvement (6% to 9% improvement), SMD –0.25 (95% CI –0.32 to –0.18)f NNTB 13 (95% CI 10 to 18)g A cross‐over study (Thorne 2008), which was not included in the meta‐analyses, showed improvement in pain in the intervention group compared to the placebo group (mean ± SD: 189.0 ± 105.0 versus 230.0 ± 115.4; P = 0.00). |
| 10 out of 100 improved by 20%c | 5 more out of 100 (3 more to 6 more) in the intervention group improved by 20%c | RR 1.50 (95% CI 1.30 to 1.60)d | ||||
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Physical function assessed with: WOMAC Physical Function (scale 0 to 1700) Follow‐up: range 1 week to 3 months |
The mean physical function was 1059 | The mean physical function in the intervention group was 68 points lower (41 lower to 99 lower)b | — | 2550 (5 RCTs) | ⊕⊕⊕⊝ Moderatee | Mean function: 4% absolute improvement (95% CI 2% to 6% improvement),b 6% relative improvement (95% CI 4% to 9% improvement),f SMD –0.20 (95% CI –0.29 to –0.12), NNTB 13 (95% CI 9 to 21)g A cross‐over study (Thorne 2008), which was not included in the meta‐analyses, showed improvement in physical function in the intervention group compared to the placebo group (mean ± SD: 632.4 ± 361.3 vs 727.4 ± 383.4; P = 0.02). |
| 16 out of 100 improved by 20%c | 5 more out of 100 (3 more to 8 more) in the intervention group improved by 20%c | RR 1.31 (95% CI 1.19 to 1.50)d | ||||
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Number of participants experiencing any adverse events Follow‐up: range 1 week to 3 months |
492 per 1000 | 659 per 1000 (610 to 718) | RR 1.34 (95% CI 1.24 to 1.46) | 2039 (4 RCTs) | ⊕⊕⊕⊝ Moderatee | 17% absolute worsening (95% CI 12% more to 23% more), 34% relative worsening (95% CI 24% more to 46% more), NNTH 6 (95% CI 5 to 9) A cross‐over study (Thorne 2008), which was not included in the meta‐analyses, showed that there was little or no difference in the total number of adverse events between the intervention group (79.8%) and placebo group (65.9%) (P = 0.08). |
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Number of participants who withdrew due to adverse events Follow‐up: range 1 week to 3 months |
73 per 1000 | 194 per 1000 (159 to 235) | RR 2.64 (95% CI 2.17 to 3.20) | 4533 (9 RCTs) | ⊕⊕⊕⊝ Moderatee | 12% absolute worsening (95% CI 9% more to 16% more), 164% relative worsening (95% CI 117% more to 220% more), NNTH 9 (95% CI 7 to 12) In a cross‐over study (Thorne 2008), which was not included in the meta‐analyses, 15 participants withdrew after randomization due to adverse events, 12 of which were in the intervention group at the time of withdrawal. |
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Number of participants experiencing any serious adverse events Follow‐up: range 1 week to 3 months |
19 per 1000 | 34 per 1000 (21 to 54) | RR 1.78 (95% CI 1.11 to 2.84) | 3612 (7 RCTs) | ⊕⊕⊝⊝ Lowe,h | 1% absolute worsening (95% CI 0% more to 4% more), 78% relative worsening (95% CI 11% more to 184% more), NNTH 68 (95% CI 29 to 477) In a cross‐over study (Thorne 2008), which was not included in the meta‐analyses, 1 serious adverse event occurred in a participant in the intervention group. |
| *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; NNTH: number needed to treat for an additional harmful outcome;RCT: randomized controlled trial;RR: risk ratio;SD: standard deviation; SE: standard error; SMD: standardized mean difference; WOMAC: Western Ontario and McMaster Universities Arthritis Index. | ||||||
| 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 SMDs and SEs, and binary outcomes expressed as RRs. We used standard inverse‐variance fixed‐effect meta‐analysis to combine the trials in Review Manager 5 (Review Manager 2014). bAbsolute improvement 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 (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. The corresponding risk was divided by the assumed risk. eDowngraded one level due to unclear risk of bias (all trials had high or unclear risk of at least one type of bias). fRelative improvement percentage defined as relative to the control group risk at baseline. gNNTB 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 CMSG Editorial office; musculoskeletal.cochrane.org/ne.org/). hDowngraded one level due to imprecision.