mRNA vaccine - versus control - for COVID-19 prophylaxis (excluding children) pdf   xlsx method abbreviations

Outcome Relative effect 95%CI LoD Trt. better when I2 k (RCT/OBS) Bayesian probability Overall ROB Publication bias Degree of certainty Endpoint importance Published MA

efficacy endpoints 00

6 months symptomatic COVID 0.09 [0.07, 0.11]< 10%1 study (1/-)100.0 %NAnot evaluable crucial-
confirmed Covid-19, from 1st dose 0.12 [0.06, 0.23]< 186%3 studies (2/1)100.0 %lownot evaluable highcrucial-
death D28 0.41 [0.37, 0.46]< 10%1 study (-/1)100.0 %NAnot evaluable crucial-
deaths 0.14 [0.07, 0.29]< 193%6 studies (2/4)100.0 %NAnot evaluable crucial-
vaccine efficacy from randomization (ITT) 0.11 [0.04, 0.29]< 191%2 studies (2/-)100.0 %some concernnot evaluable moderatecrucial-
confirmed COVID (any severity) 0.21 [0.13, 0.33]< 198%12 studies (-/12)100.0 %NAlow important-
death or ventilation 0.56 [0.46, 0.68]< 10%1 study (-/1)100.0 %NAnot evaluable important-
hospitalization 0.11 [0.06, 0.20]< 199%9 studies (-/9)100.0 %lownot evaluable highimportant-
symptomatic Covid-19 0.14 [0.07, 0.27]< 1100%19 studies (2/17)100.0 %lowcritical highimportant-
6 months severe COVID-19 0.03 [0.00, 0.46]< 10%1 study (1/-)99.4 %NAnot evaluable non important-
asymptomatic COVID case 0.16 [0.08, 0.35]< 191%4 studies (-/4)100.0 %NAnot evaluable non important-
infection (PCR positive symptomatic or not) 0.16 [0.10, 0.26]< 198%11 studies (-/11)100.0 %lowcritical highnon important-
severe COVID-19 occurrence 0.08 [0.04, 0.15]< 196%11 studies (2/9)100.0 %moderatelow moderatenon important-
transmission (symptomatic confirmed COVID19) 0.53 [0.48, 0.58]< 10%2 studies (-/2)100.0 %seriousnot evaluable lownon important-
vaccine efficacy after dose 1 (and before dose 2) 0.30 [0.22, 0.41]< 176%8 studies (1/7)100.0 %lownot evaluable highnon important-

safety endpoints 00

cerebrovascular thromboembolic events 0.84 [0.55, 1.29]< 10%1 study (-/1)78.8 %NAnot evaluable important-
related AE (TRAE) 4.91 [4.58, 5.26]< 10%1 study (1/-)0.0 %NAnot evaluable important-
related SAE (TRSAE) 8.00 [0.42, 151.43]< 10%1 study (1/-)8.5 %NAnot evaluable important-
serious adverse events 1.10 [0.90, 1.33]< 10%2 studies (2/-)17.7 %some concernnot evaluable moderateimportant-
acute kidney injury 0.44 [0.25, 0.78]< 10%1 study (-/1)99.7 %NAnot evaluable non important-
adverse events 1.73 [0.77, 3.91]< 1100%2 studies (2/-)9.4 %some concernnot evaluable moderatenon important-
Anemia 0.79 [0.67, 0.93]< 10%1 study (-/1)99.8 %NAnot evaluable non important-
arrhythmia 0.89 [0.75, 1.06]< 10%1 study (-/1)91.0 %NAnot evaluable non important-
Arthritis or arthropathy 0.95 [0.66, 1.36]< 10%1 study (-/1)60.9 %NAnot evaluable non important-
convulsions/seizures 1.03 [0.85, 1.26]< 10%2 studies (-/2)37.8 %criticalnot evaluable very lownon important-
deep vein thrombosis 0.87 [0.55, 1.39]< 10%1 study (-/1)72.0 %NAnot evaluable non important-
disseminated intravascular coagulation 0.70 [0.39, 1.27]< 10%1 study (-/1)88.0 %NAnot evaluable non important-
Guillain-Barré syndrome 0.83 [0.56, 1.22]< 10%3 studies (-/3)83.2 %NAnot evaluable non important-
Herpes simplex infection 1.13 [0.94, 1.36]< 10%1 study (-/1)10.0 %NAnot evaluable non important-
herpes zoster infection 1.25 [0.94, 1.66]< 173%2 studies (-/2)6.3 %moderatenot evaluable moderatenon important-
immune thrombocytopenia 2.60 [0.39, 17.24]< 10%1 study (-/1)16.2 %NAnot evaluable non important-
intracranial hemorrhage 0.83 [0.33, 2.08]< 183%2 studies (-/2)65.4 %moderatenot evaluable moderatenon important-
ischemic stroke 0.98 [0.89, 1.07]< 10%2 studies (-/2)70.1 %criticalnot evaluable very lownon important-
life-threatening SAE 0.91 [0.51, 1.65]< 10%1 study (1/-)61.8 %NAnot evaluable non important-
Myocardial infarction 1.04 [0.93, 1.16]< 10%3 studies (-/3)24.9 %criticalnot evaluable very lownon important-
myocarditis 1.98 [1.09, 3.60]< 180%4 studies (-/4)1.3 %moderatenot evaluable moderatenon important-
neutropenia 0.87 [0.46, 1.65]< 10%1 study (-/1)66.5 %NAnot evaluable non important-
paresthesia 1.18 [1.09, 1.28]< 120%2 studies (-/2)0.0 %moderatenot evaluable moderatenon important-
pericarditis 1.21 [0.86, 1.70]< 10%2 studies (-/2)13.9 %criticalnot evaluable very lownon important-
pulmonary embolism 1.03 [0.86, 1.24]< 129%3 studies (-/3)36.6 %criticalnot evaluable very lownon important-
severe adverse events 1.74 [1.41, 2.14]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
thrombocytopenia 0.94 [0.66, 1.33]< 10%1 study (-/1)63.5 %NAnot evaluable non important-
Transverse myelitis 1.45 [0.07, 31.68]< 10%1 study (-/1)40.8 %NAnot evaluable non important-
uveitis 1.27 [0.64, 2.52]< 10%1 study (-/1)24.7 %NAnot evaluable non important-
venous thromboembolism 1.16 [1.00, 1.34]< 10%1 study (-/1)2.3 %NAnot evaluable non important-
VTE with thrombocytopenia 0.86 [0.58, 1.27]< 10%1 study (-/1)77.5 %NAnot evaluable non important-

AE of interest endpoints 00

cerebral venous sinus thrombosis (CVST) 1.37 [0.47, 3.95]< 10%3 studies (-/3)28.2 %moderatenot evaluable moderateimportant-
appendicitis 1.09 [0.69, 1.72]< 171%4 studies (2/2)35.2 %criticalnot evaluable very lownon important-
arthralgia, grade 3-4 18.37 [13.54, 24.91]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
Bell's palsy 1.06 [0.89, 1.26]< 161%11 studies (2/9)26.3 %lowlow highnon important-
hypersensitivity, all terms 1.43 [1.18, 1.74]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
immediate allergic reaction 1.00 [0.02, 50.42]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
lymphadenopathy, any 4.80 [1.13, 20.41]< 191%2 studies (1/1)1.7 %seriousnot evaluable lownon important-
lymphadenopathy, grade 3-4 1.00 [0.06, 15.97]< 10%1 study (1/-)50.0 %NAnot evaluable non important-
musculoskeletal and connective tissue disorders, any 3.64 [3.25, 4.08]< 10%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
myalgia, grade 3-4 27.64 [20.93, 36.50]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
myelitis 1.05 [0.77, 1.43]< 114%2 studies (-/2)37.5 %NAnot evaluable non important-

reactogenicity (vaccines) endpoints 00

fever, grade 3-4 43.29 [17.83, 105.10]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
local adverse reaction, any, dose 1 24.90 [22.13, 28.03]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
local adverse reaction, any, dose 2 27.99 [19.26, 40.68]< 196%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
local adverse reaction, grade 3-4, dose 2 15.04 [11.83, 19.12]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
systemic adverse reaction, any, dose 1 1.63 [1.50, 1.78]< 10%1 study (1/-)0.0 %NAnot evaluable non important-
systemic adverse reaction, any, dose 2 5.53 [3.79, 8.06]< 198%2 studies (2/-)0.0 %some concernnot evaluable moderatenon important-
systemic adverse reaction, grade 3-4, dose 2 9.50 [8.38, 10.77]< 10%1 study (1/-)0.0 %NAnot evaluable non important-

immunogenicity (vaccines) endpoints 00

serologic response (seroconversion) 0.09 [0.00, 5.02]> 170%2 studies (-/2)12.4 %NAnot evaluable non important-

LoD: level of statistical demonstration: Statistically conclusive: statistically significant with a strict control of overall risk of type 1 error (statistically demonstrated), does not take into account the risk of bias; suggested: nominally statistically significant but without a strict control of overall risk of type 1 error; inconclusive: not nominally statistically significant; safety concerns;
Bayesian probability: Bayesian posterior probability of treatment effect (computed with a noninformative prior); ROB: risk of bias; k: number of studies; published MA: number of published meta-analysis on the same topic; degree of certainty adapted from GRADE. Trt. better when: indicates when the relative treatment effect shows that the studied treatment is better than control.