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:ย 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. Wang 2020, ACTT Beigel 2020, Spinner 2020 , Solidarity 2021, Mahajan 2021
b. Downgraded by one for level serious indirectness; The usage of steroids varied across the studies
c. Downgraded by one level for serious imprecision; the 95% CI is wide
d. ACTT Beigel 2020, Spinner 2020. Pooled estimate is from 2 trials at 10 days
e. Downgraded by one level for serious risk of bias; Spinner 2020 was at high risk of bias and contributed to 36.1% of the weight in the meta-analysis
f. Downgraded by one level for serious indirectness; Spinner 2020 had moderate severity patients only and ACTT Beigel 2020 had a mixture of patients of different severity.
g. Downgraded by two levels for very serious imprecision; It is difficult to determine the clinical significance of the difference in the time to clinical improvement with hazard ratios, but the 95% CI was wide and included no difference.
h. Wang 2020, ACTT Beigel 2020 , Spinner 2020. Pooled estimate from 3 trials at 10 days
i. Downgraded by one level for serious risk of bias ; Spinner 2020 was at high risk of bias and contributed 25.9% of the weight to the pooled effect estimate.
j. Downgraded by one level for serious indirectness; The three studies included patients with different grades of disease severity and Spinner 2020 included only patients with moderate severity.
k. ACTT Beigel 2020
l. Downgraded by two levels for imprecision; 95% CI is very wide
m. Downgraded by one level serious indirectness; as very few people in ACTT Beigel 2020 were given steriods
n. Downgraded by one level for serious imprecision.The data were from only one trial and the number of events were too few to satisfy the requirements for the optimal information size (OIS) [The OIS for a RRR of 2 percent needs at least 700 events for the intervention to be significant (Remdesivir arm: 52/307, placebo arm: 64/266)]. The 95% CI of the effect estimate included clinically important and potentially clinically non-appreciable benefits with Remdesivir.
o. ACTT Beigel 2020, Solidarity 2021
p. Downgraded by two levels for very serious inconsistency; the I2 is 91%.