Table 3.
Summary of findings including GRADE quality assessment of evidence trials with lower risk of bias
| Variables | No of participants (No of studies) | No with event/No in group (%) | Relative risk (95% CI) | Absolute effect | Quality of the evidence (GRADE) | Quality assessment domains | |
|---|---|---|---|---|---|---|---|
| Restrictive transfusion group | Liberal transfusion group | ||||||
| All cause mortality, longest follow-up, low risk of bias trials | 5707 (9) | 445/2860 (15.6) | 495/2847 (17.4) | Random effects 0.86 (0.74 to 1.01); I2=27%; trial sequential analysis adjusted 95% CI 0.67 to 1.12 | 24 fewer per 1000 (from 45 fewer to 2 more) | Low; critical importance | Inconsistency: not serious*; indirectness: not serious; imprecision: serious†; reporting bias: reporting bias‡ |
| Overall morbidity, lower risk of bias trials | 4517 (6) | 858/2261 (37.9) | 897/2256 (39.8) | Random effects 0.98 (0.85 to 1.12); I2=60%; trial sequential analysis adjusted 95% CI 0.81 to 1.19 | 8 fewer per 1000 (from 60 fewer to 48 more) | Very low; critical importance | Inconsistency: serious§; indirectness: not serious; imprecision: serious¶; reporting bias: reporting bias‡ |
| Fatal and non-fatal myocardial infarction in lower risk of bias trials | 4730 (7) | 59/2369 (2.5) | 43/2361 (1.8) | Random effects 1.28 (0.66 to 2.49); I2=34%; trial sequential analysis adjusted 95% CI 0.40 to 4.13 | 6 more per 1000 (from 6 fewer to 27 more) | Very low; critical importance | Inconsistency: serious**; indirectness: not serious; imprecision: very serious††; reporting bias: reporting bias‡ |
GRADE Working Group grades of evidence: low quality=further research is likely to have an important impact on confidence in estimate of effect and is likely to change the estimate; very low quality=very uncertain about the estimate.
Quality assessment domains: inconsistency=unexplained heterogeneity of results; indirectness=differences in population, intervention, comparator, and outcome measures; imprecision=relatively few patients and few events resulting in wide confidence intervals; reporting bias=publication bias is a systematic under-estimation or over-estimation of underlying beneficial or harmful effect owing to selective publication of trial results.
*I2=27%, P=0.20for heterogeneity, overlap of confidence intervals.
†Anticipation of 15% relative risk reduction results in trial sequential analysis adjusted confidence intervals, including >25% relative risk reduction or >25% relative risk increase. However, <15% relative risk reduction or relative risk increase may also be considered clinically relevant and these are apparently not excluded in any analyses.
‡Possibility for publication bias according to funnel plot owing to smaller trials showing benefit for restrictive transfusion strategy.
§I2=60%, P=0.03 for heterogeneity, overlap of confidence intervals.
¶Two trials showed no effect and appreciable harm with restrictive transfusion strategy.
**I2=34%, P=0.11 for heterogeneity, variance in point estimates, from 0.25 to 2.97.
††6 of 7 trials showed no effect and appreciable harm with restrictive transfusion strategy.