Summary of findings 2. RV1 compared to placebo for preventing rotavirus diarrhoea in high‐mortality countries.
| Patient or population: children Settings: high‐mortality countries (WHO strata D and E) Intervention: RV1 Comparison: placebo or no intervention | ||||||
| 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 or no intervention | RV1 | |||||
| Severe cases of rotavirus diarrhoea Follow‐up: up to 1 year | 60 per 1000 | 22 per 1000 (14 to 36) | RR 0.37 (0.23 to 0.60) | 6114 (3 studies) | ⊕⊕⊕⊕ high | RV1 reduces severe rotavirus diarrhoea compared to placebo or no intervention at up to one year follow‐up. We did not downgrade for inconsistency as the heterogeneity observed in the pooled data (I2 statistic = 57%) was due to within‐study heterogeneity (RV1 Madhi 2010‐AF results split by country) |
| Severe cases of rotavirus diarrhoea Follow‐up: up to 2 years | 43 per 1000 | 28 per 1000 (22 to 35) | RR 0.65 (0.51 to 0.83) | 13,768** (2 studies) | ⊕⊕⊕⊕ high | RV1 reduces severe rotavirus diarrhoea compared to placebo or no intervention at up to two years follow‐up. Sensitivity analysis excluding the cluster‐RCT (RV1 Zaman 2017‐BGD) that contributed data to this outcome showed no significant change in effect estimate or 95% CI (RR 0.58, 95% CI 0.42 to 0.79, n = 2764, 1 RCT) |
| Severe cases of all‐cause diarrhoea Follow‐up: up to 1 year | 176 per 1000 | 129 per 1000 (99 to 167) | RR 0.73 (0.56 to 0.95) | 5639 (2 studies) | ⊕⊕⊕⊕ high | RV1 reduces severe all‐cause diarrhoea compared to placebo or no intervention at up to one year follow‐up. We did not downgrade for inconsistency as the heterogeneity observed in the pooled data (I2 statistic = 75%) was due to within‐study heterogeneity (RV1 Madhi 2010‐AF results split by country) |
| Severe cases of all‐cause diarrhoea Follow‐up: up to 2 years | 233 per 1000 | 191 per 1000 (166 to 222) | RR 0.82 (0.71 to 0.95) | 2764 (1 study) | ⊕⊕⊕⊝
moderatea due to indirectness |
RV1 probably slightly reduces severe all‐cause diarrhoea compared to placebo or no intervention at up to two years follow‐up. |
| All‐cause death Follow‐up: 2 months to 2 years | 24 per 1000 | 21 per 1000 (16 to 30) | RR 0.88 (0.64 to 1.22) | 8181 (8 studies) | ⊕⊕⊝⊝
lowb due to imprecision |
RV1 may make little or no difference to all‐cause death compared to placebo or no intervention. |
| All serious adverse events Follow‐up: 2 months to 2 years | 95 per 1000 | 84 per 1000 (72 to 99) | RR 0.89 (0.76 to 1.04) | 7481 (7 studies) | ⊕⊕⊕⊕ high | RV1 makes little or no difference to serious adverse events compared to placebo or no intervention. |
| Serious adverse events: intussusception Follow‐up: 2 months to 2 years | 0 per 100,000 | 0 per 100,000 (0 to 0) | RR 1.49 (0.06 to 36.63) | 17,492** (4 studies) | ⊕⊕⊝⊝
lowc due to imprecision |
RV1 may make little or no difference to intussusception compared to placebo or no intervention. Sensitivity analysis excluding the cluster‐RCT (RV1 Zaman 2017‐BGD) that contributed data to this outcome showed no change in effect estimate or 95% CI |
| *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). **Number of participants in this table shows the true number of participants for this outcome; the number of events and the number of participants in the analysis has been adjusted for the included cluster trial RV1 Zaman 2017‐BGD using a design effect of 2.53. 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. | ||||||
aDowngraded by one for indirectness. Trials were conducted in Malawi and South Africa, so generalization to any high‐mortality country is difficult. bDowngraded by two for imprecision. These trials were not powered to detect an effect on mortality. cDowngraded 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.