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. Gordon REMAP-CAP 2021 [3]; Hermine CORIMUNO-19 2020 [4]; Horby RECOVERY 2021 [5]; Rosas COVACTA 2021 [6]; Salama EMPACTA 2020 [7]; Salavarani 2020 [8]; Soin COVINTOC 2021 [9]; Stone 2020 [10]; Veiga TOCIBRAS 2021 [11]
b. Not downgraded for risk of bias: We feel the imbalance in the proportions of Remdesivir, used as a co-intervention, in the two groups is unlikely to affect the outcome.
c. Not downgraded for indirectness: The majority of participants had severe or critical illness in the REMAP-CAP and RECOVERY trials, which contributed the most data to this meta-analysis.
d. Downgraded by 1 level for serious imprecision, since the upper bound of the 95% CI includes clinical benefit that may not be appreciable in clinical practice.
e. Gordon REMAP-CAP 2021 [3]; Hermine CORIMUNO-19 2020 [4]; Horby RECOVERY 2021 [5]; Rosas COVACTA 2021 [6]; Salama EMPACTA 2020 [7]; Salvarani 2020 [8]; Stone 2020 [10]; Veiga TOCIBRAS 2021 [11]
f. Downgraded by 1 level for serious risk of bias: some concerns due to deviation from intended interventions, outcome measurement and selection of reported results
g. Downgraded by 1 level for serious indirectness, since the outcome is a composite outcome of in-hospital survival, hospital discharge, 2-point ordinal scale improvement
h. Gordon REMAP-CAP 2021 [3]; Hermine CORIMUNO-19 2020 [4]; Horby RECOVERY 2021 [5]; Rosas COVACTA 2021 [6]; Salama EMPACTA 2020 [7]; Salvarani 2020 [8]; Stone 2020 [10]
i. Gordon REMAP-CAP 2021 [3]; Hermine CORIMUNO-19 2020 [4]; Horby RECOVERY 2021 [5]; Salama EMPACTA 2020 [7]; Stone 2020 [10]; Veiga TOCIBRAS 2021 [11]
j. Hermine CORIMUNO-19 2020 [4]; Rosas COVACTA 2021 [6]; Salama EMPACTA 2020 [7]; Salvarani 2020 [8]; Soin COVINTOC 2021 [9]; Stone 2020 [10]; Veiga TOCIBRAS 2021 [11]; Wang 2021 [12]
k. Downgraded by 1 level for serious risk of bias: some concerns regarding randomization, deviations from intended interventions and outcome measurement
l. Downgraded by 1 level for serious inconsistency: I²=64%
m. Downgraded by 1 level for serious imprecision due to a wide confidence interval consistent with the possibility for no effect and the possibility for harm
n. Gordon REMAP-CAP 2021 [3]; Hermine CORIMUNO-19 2020 [4]; Rosas COVACTA 2021 [6]; Salama EMPACTA 2020 [7]; Salvarani 2020 [8]; Soin COVINTOC 2021 [9]; Stone 2020 [10]; Veiga TOCIBRAS 2021 [11]; Wang 2020 [12]
o. Downgraded by 1 level for serious risk of bias: some concerns regarding randomization, deviations from intended interventions and outcome measurement
p. Downgraded by 1 level for serious indirectness: the absolute estimates of serious adverse events varied between trials, for e.g. 30% to 40% for the Rosas COVACTA 2021 trial [6] and about 3% for the Gordon REMAP-CAP 2021 trial [3]