Summary of findings for the main comparison. Ursodeoxycholic acid compared with placebo or no intervention for primary biliary cirrhosis.
| Ursodeoxycholic acid compared with placebo or no intervention for primary biliary cirrhosis | ||||||
| Patient or population: patients with primary biliary cirrhosis. Settings: out‐patients. Intervention: ursodeoxycholic acid. Comparison: placebo or no intervention. | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | No of Participants (studies) | Quality of the evidence (GRADE) | Comments | |
| Assumed risk | Corresponding risk | |||||
| Control | UDCA versus placebo or no intervention | |||||
| All‐cause mortality | Study population | RR 0.97 (0.67 to 1.42) | 1391 (14 trials) | ⊕⊝⊝⊝ very low1 | ||
| 66 per 1000 | 64 per 1000 (45 to 94) | |||||
| All‐cause mortality or liver transplantation | Study population | RR 0.96 (0.74 to 1.25) | 1419 (15 trials) | ⊕⊝⊝⊝ very low1,2 | ||
| 126 per 1000 | 121 per 1000 (93 to 158) | |||||
| Serious adverse events | Study population | RR 0.87 (0.68 to 1.12) | 1382 (14 trials) | ⊕⊝⊝⊝ very low1,2 | ||
| 156 per 1000 | 136 per 1000 (106 to 174) | |||||
| Non‐serious adverse events | Study population | RR 1.46 (0.83 to 2.56) | 1277 (12 trials) | ⊕⊝⊝⊝ very low1,2 | ||
| 28 per 1000 | 41 per 1000 (24 to 73) | |||||
| Pruritus | Study population | RR 0.96 (0.84 to 1.09) | 630 (6 trials) | ⊕⊕⊝⊝ low1,3 | ||
| 537 per 1000 | 516 per 1000 (451 to 586) | |||||
| Serum bilirubin (µmol/l) | The mean serum bilirubin concentration in the intervention groups was 8.69 lower (13.9 to 3.48 lower) | 881 (9 trials) | ⊕⊕⊝⊝ low1,4,5 | |||
|
Liver biopsy findings (worsening of histological stage) |
Study population | RR 0.62 (0.44 to 0.88) | 551 (7 trials) | ⊕⊝⊝⊝ very low1,2,6 | ||
| 381 per 1000 | 237 per 1000 (168 to 336) | |||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (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). CI: Confidence interval; RR: Risk ratio. | ||||||
| GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate. | ||||||
1 Plausible bias that raises some doubt about the results. Potential limitations are likely to lower confidence in the estimate of effect. 2 Total sample size is lower than the calculated optimal information size (OIS) and total number of events is less than 300 (a threshold rule‐of‐thumb value). So, we have little knowledge about the intervention effect and further information is needed. 3 Total sample size is lower than the calculated optimal information size (OIS) but the total number of events is not less than 300 (a threshold rule‐of‐thumb value). Anyway, we have little knowledge about the intervention effect and further information is needed. 4 Serum bilirubin concentration is a surrogate endpoint instead of patient‐important outcome. 5 Total sample size is lower than the calculated optimal information size (OIS). On the other hand, according to the results of trial sequential analysis there is a evidence for a beneficial effect of ursodeoxycholic acid versus placebo or no intervention on serum bilirubin concentration when the cumulative meta‐analysis is adjusted for sparse data and multiple testing on accumulating data. Therefore, there is no risk for random errors. 6 Statistical heterogeneity I2 = 35%.