Summary of findings:

mRNA-1273 compared to Placebo for vaccination against COVID-19

Patient or population:
Setting:
Intervention:
Comparison:

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

Incidence of participants with positive test for SARS-CoV-2 infection - not reported
-
-
-
-
-
outcome not yet measured or reported
Incidence of symptomatic COVID-19 confirmed with positive test for SARS-CoV-2 b,c
1,315 per 100,000
79 per 100,000
(39 to 145)
Rate Ratio 0.06
(0.03 to 0.11)
28207
(1 RCT)
d

MODERATE
e,f,g
Vaccine efficacy 94.1% (95%CI 89.3% to 96.8%) h
Incidence of hospitalization or death due to confirmed COVID- 19 - not reported
-
-
-
-
-
outcome not yet measured or reported
Severe or critical disease due to COVID-19 b,c
213 per 100,000
4 per 100,000
(0 to 58)
RR 0.02
(0.00 to 0.27)
28207
(1 RCT)
d

LOW
f,g,i
Vaccine efficacy: 100% (95%CI NE to 100%) j
All-cause mortality k,l
46 per 100,000
40 per 100,000
(13 to 118)
RR 0.86
(0.29 to 2.55)
30351
(1 RCT)
d

VERY LOW
f,g,m
Incidence of any adverse events l,n
21,608 per 100,000
23984 per 100,000
(22,904 to 24,849)
RR 1.11
(1.06 to 1.15)
30351
(1 RCT)
d

MODERATE
g
Incidence of serious adverse events (SAEs) l
1,009 per 100,000
968 per 100,000
(777 to 1,211)
RR 0.96
(0.77 to 1.20)
30351
(1 RCT)
d

MODERATE
g
*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).

CI: Confidence interval; RR: Risk ratio
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

Explanations

a. Last updated: January 25, 2021
b. more than 14 days after Dose 2
c. Median follow-up time: 9 weeks
d. ModernaTX: Baden LR, COVE, 2020
e. Despite some concerns with deviations from intervention, not downgraded for risk of bias.
f. Despite a multicentre design this is a single study from a single country, so results in this population might not be generalizable to other settings. However, we have not downgraded for indirectness as there is limited evidence to suggest efficacy may differ in other settings.
g. Indirectness downgraded by one level: data are from an interim analysis of the trial, with a short duration of follow-up. Estimates may change over a longer duration of follow-up.
h. Vaccine efficacy in 18-64y: 95.60% (95%CI 90.60 to 97.90); Vaccine efficacy in >=64 y: 86% (95% CI 61.40 to 95.20)
i. Imprecision downgraded by one level: due to small number of events observed
j. NE: not estimable
k. up to December 3rd, 2020; data taken from the FDA briefing
l. Overall median follow-up time: two months after Dose 2
m. Imprecision downgraded by two levels: due to small number of events observed and a wide 95% confidence interval that encompasses a potential benefit and a potential harm with the intervention.
n. only unsolicited adverse events