Summary of findings 2. mRNA‐1273 – ModernaTX compared to placebo for vaccination against COVID‐19a.
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with placebo | Risk with mRNA‐1273 | |||||
| Confirmed SARS‐CoV‐2 infectionb | 8957 per 100,000 | 2394 per 100,000 (997 to 5749) | VE 73.27 (35.82 to 88.87) | 31,632 (2 RCTs)c | ⨁⨁⨁◯ Moderated,e | Substantial heterogeneity (I² = 66%) between included studies: Ali 2021 (adolescents aged 12–17 years, median 2.3 months' follow‐up): VE 55.7% (95% CI 16.8 to 76.4), n = 3181; El Sahly 2021 (adults aged 18–95 years, 5.3 months' follow‐up): VE 82% (95% CI 79.5 to 84.2), n = 28,451 |
| Confirmed symptomatic COVID‐19 b | 4939 per 100,000 | 336 per 100,000 (255 to 442) |
VE 93.20 (91.06 to 94.83) |
31,632 (2 RCTs)c | ⨁⨁⨁⨁ Highd | — |
| Severe or critical COVID‐19f | 748 per 100,000 | 13 per 100,000 (3 to 54) |
VE 98.20 (92.80 to 99.60) |
28,451 (1 RCT)g | ⨁⨁⨁⨁ Highd | — |
| All‐cause mortalityf | 106 per 100,000 | 112 per 100,000 (57 to 222) |
RR 1.06 (0.54 to 2.10) | 30,346 (1 RCT)g | ⨁⨁◯◯ Lowh | 1 additional trial: (Ali 2021 (adolescents aged 12–17 years)) reported on this outcome in 3726 participants (2486 mRNA‐1273 and 1240 placebo). There were no events in either group and the trial did not contribute to the pooled effect estimate |
| Systemic reactogenicity eventsi | 432 per 1000 | 553 per 1000 (527 to 579) | RR 1.28 (1.22 to 1.34) | 34,037 (2 RCTs)c | ⨁⨁⨁⨁ Highj | — |
| Any adverse eventk | Outcome not pooled due to considerable heterogeneity (I² = 100%) between included studies: Ali 2021 (all solicited adverse events, adolescents aged 12–17 years, median 2.8 months' follow‐up): RR 1.47 (95% CI 1.41 to 1.54), n = 3726; El Sahly 2021 (all solicited adverse events, adults aged 18–95 years, 5.3 months' follow‐up): RR 2.15 (95% CI 2.11 to 2.19), n = 29,269 | — | 32,995 (2 RCTs)c | ⨁⨁◯◯ Lowl | — | |
| Serious adverse eventsl | 1792 per 100,000 | 1649 per 100,000 (1398 to 1936) | RR 0.92 (0.78 to 1.08) | 34,072 (2 RCTs)c | ⨁⨁⨁◯ Moderatem | — |
| Local reactogenicity eventsi | 211 per 1000 | 697 per 1000 (427 to 1000) | RR 3.30 (2.02 to 5.40) | 34,037 (2 RCTs)c | ⨁⨁⨁⨁ Highn | — |
| *The risk in the intervention group (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). COVID‐19: coronavirus disease 2019; CI: confidence interval; RCT: randomized controlled trial; RR: risk ratio; SARS‐CoV‐2: severe acute respiratory syndrome coronavirus 2; VE: vaccine efficacy. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect. | ||||||
a. Last updated: 01 March 2023
b. Follow‐up: from 14 days after dose 2 to 2.3 months (median) and 5.3 months
c. Moderna TX: Ali 2021 (adolescents aged 12–17 years); El Sahly 2021 (adults aged 18–95 years)
d. Despite some concerns with deviations from intervention, not downgraded for risk of bias
e. Inconsistency: downgraded one level: I² = 66.37%
f. Follow‐up: 5.3 months
g. Moderna TX: El Sahly 2021 (adults aged 18–95 years)
h. Imprecision downgraded two levels due to small number of events observed and wide CIs that encompass a potential benefit and a potential harm with the intervention
i. Follow‐up: seven days
j. Despite inconsistency (I² = 61%) not downgraded for inconsistency, as the same direction of effect in both effect estimates
k. Follow‐up: 2.8 months (median) and 5.3 months
l. Inconsistency: downgraded two levels (I² = 100%)
m. Imprecision: downgraded one level due to wide CIs that encompass a potential benefit and a potential harm with the intervention.
n. Despite inconsistency (I² = 99%), not downgraded for inconsistency, as the same direction of effect in both effect estimates