Table 1. Summary of findings - children with a serious adverse event.
| Comparison | Illustrative comparative risks * (95% CI) | Relative effect (95% CI) | No of participants (studies) | Quality of the evidence (GRADE) | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Control | Regular LABA (salmeterol or formoterol) | |||||
| Children with a fatal serious adverse event of any cause | ||||||
| All comparisons | see comment | see comment | see comment | see comment | see comment | There was only a single child who died in all the studies so mortality could not be assessed |
| Children with a non-fatal serious adverse event of any cause | ||||||
| Regular formoterol versus placebo Cates 2012a Follow-up: mean 27 weeks | 12 per 1000 | 30 per 1000 (15 to 56) | OR 2.48 (1.27 to 4.83) | 1335 (5 studies) | ⊕⊕⊕⊕ high | |
| Regular salmeterol versus placebo Cates 2008 Follow-up: mean 31 weeks | 56 per 1000 | 72 per 1000 (46 to 108) | OR 1.3 (0.82 to 2.05) | 1333 (5 studies) | ⊕⊕⊕○ moderate 1 | |
| Regular formoterol & ICS versus ICS Cates 2009b Follow-up: mean 13 weeks | 8 per 1000 | 14 per 1000 (7 to 27) | OR 1.62 (0.80 to 3.28) | 2788 (7 studies) | ⊕⊕⊕○ moderate 1 | |
| Regular salmeterol & ICS versus ICS Cates 2009a Follow-up: mean 15 weeks | 5 per 1000 | 6 per 1000 (2 to 19) | OR 1.20 (0.37 to 3.91) | 1862 (5 studies) | ⊕⊕⊕○ moderate 1 | |
| Regular formoterol versus regular salmeterol Cates 2012b Follow-up: 13 weeks | 13 per 1000 (on salmeterol) | 12 per 1000 (1 to 168) (on formoterol) | OR 0.95 (0.06 to 15.33) | 156 (1 study) | ⊕⊕○○ low 1,2 | Formoterol was considered the active treatment and salmeterol the control treatment for this comparison |
| Children with a non-fatal serious adverse event related to asthma | ||||||
| Regular formoterol versus placebo Cates 2012a Follow-up: mean 27 weeks | 2 per 1000 | 8 per 1000 (4 to 18) | OR 4.06 (1.78 to 9.22) | 1335 (5 studies) | ⊕⊕⊕⊕ high | |
| Regular salmeterol versus placebo Cates 2008 Follow-up: mean 31 weeks | 33 per 1000 | 55 per 1000 (33 to 92) | OR 1.72 (1 to 2.98) | 1333 (5 studies) | ⊕⊕⊕⊕ high | |
| Regular formoterol & ICS versus ICS Cates 2009b Follow-up: mean 13 weeks | 4 per 1000 | 6 per 1000 (2 to 17) | OR 1.49 (0.48 to 4.61) | 2788 (7 studies) | ⊕⊕ low 1,3 | |
| Regular salmeterol & ICS versus ICS Cates 2009a Follow-up: mean 15 weeks | 1 per 1000 | 1 per 1000 (0 to 17) | OR 0.99 (0.06 to 15.85) | 1862 (5 studies) | ⊕⊕○○ low 1,3 | |
The basis for the assumed risk (was the mean control group risk across studies). 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; OR: Odds ratio; SAE: serious adverse event
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.
Confidence intervals include the possibility of an increase and a decrease in SAEs on regular LABA
Single unblinded study
Considerable heterogeneity between trial results