Summary of findings for the main comparison. RV1 compared to placebo for preventing rotavirus diarrhoea in low‐mortality countries.
Patient or population: children Setting: low‐mortality countries (WHO strata A and B) Intervention: RV1 Comparison: placebo | ||||||
Outcomes | Illustrative comparative risks* (95% CI) | Relative effect (95% CI) | Number of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
Assumed risk | Corresponding risk | |||||
Placebo | RV1 | |||||
Severe cases of rotavirus diarrhoea Follow‐up: up to 1 year | 13 per 1000 | 2 per 1000 (1 to 3) | RR 0.16 (0.09 to 0.26) | 43,779 (7 studies) | ⊕⊕⊕⊕ higha | RV1 reduces severe rotavirus diarrhoea compared to placebo at up to one year follow‐up. One study (RV1 Vesikari 2007a‐EU) reported higher efficacy compared to the pooled data. When we excluded this study from the analysis, there was no heterogeneity observed in the pooled data |
Severe cases of rotavirus diarrhoea Follow‐up: up to 2 years | 24 per 1000 | 4 per 1000 (3 to 5) | RR 0.18 (0.14 to 0.23) | 36,002 (9 studies) | ⊕⊕⊕⊕ high | RV1 reduces severe rotavirus diarrhoea compared to placebo at up to two years follow‐up. |
Severe cases of all‐cause diarrhoea Follow‐up: up to 1 year | 41 per 1000 | 24 per 1000 (19 to 30) | RR 0.59 (0.47 to 0.74) | 28,051 (3 studies) | ⊕⊕⊕⊝
moderateb due to reporting bias |
RV1 probably reduces severe all‐cause diarrhoea compared to placebo at up to one year follow‐up. |
Severe episodes of all‐cause diarrhoea Follow‐up: up to 2 years | 39 per 1000 | 24 per 1000 (22 to 28) | Rate Ratio 0.63 (0.56 to 0.71) | 39,091 (2 studies) | ⊕⊕⊕⊝
moderatec due to reporting bias |
RV1 probably reduces severe all‐cause diarrhoea compared to placebo at up to two years follow‐up. Three additional studies reported on cases of children with severe all‐cause diarrhoea (RR 0.60, 95% CI 0.36 to 1.02; 9417 participants); these data could not be pooled with the studies reporting on number of episodes |
All‐cause death Follow‐up: 2 months to 2 years | 1 per 1000 | 2 per 1000 (1 to 2) | RR 1.22 (0.87 to 1.71) | 97,597 (22 studies) | ⊕⊕⊝⊝
lowd due to imprecision |
RV1 may make little or no difference to all‐cause death compared to placebo. |
All serious adverse events Follow‐up: 2 months to 2 years | 45 per 1000 | 40 per 1000 (37 to 42) | RR 0.88 (0.83 to 0.93) | 96,233 (24 studies) | ⊕⊕⊕⊕ high | RV1 slightly reduces serious adverse events compared to placebo. |
Serious adverse events: intussusception Follow‐up: 2 months to 2 years | 1 per 1000 | 1 per 1000 (0 to 1) | RR 0.69 (0.45 to 1.04) | 96,513 (17 studies) | ⊕⊕⊝⊝
lowe due to imprecision |
RV1 may make little or no difference to intussusception compared to placebo. |
*The basis for the assumed risk is the control group risk across studies included in the meta‐analysis. The corresponding risk (and its 95% CI) 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‐certainty: further research is very unlikely to change our confidence in the estimate of effect. Moderate‐certainty: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low‐certainty: 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‐certainty: we are very uncertain about the estimate. |
aWe observed heterogeneity (I2 statistic = 61%) in the pooled data, but given the strength of the evidence, and that estimates were all in the same direction, we did not downgrade the outcome. bDowngraded by one for risk of selective reporting bias. Only three of the seven studies reporting on severe rotavirus diarrhoea provided data for this outcome. cDowngraded by one for risk of selective reporting bias. Only five of the nine studies reporting on severe rotavirus diarrhoea provided data for this outcome. dDowngraded by two for imprecision. These trials were not powered to detect an effect on mortality. eDowngraded by two for imprecision. There was a 1:10,000 to 1:32,000 increased risk of intussusception with a previous rotavirus vaccine (Bines 2005), so these trials were not powered to detect an association between RV1 and intussusception.