Intravenous vitamin C monotherapy in critically ill patients: a systematic review and meta-analysis of randomized controlled trials with trial sequential analysis

Annals of Intensive Care

Table 3 GRADE certainty assessment and summary of findings table for overall mortality

Certainty assessment							Summary of findings
Participants (studies) follow-up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall certainty of evidence	Study event rates (%)		Relative effect (95% CI)	Anticipated absolute effects
Participants (studies) follow-up	Risk of bias	Inconsistency	Indirectness	Imprecision	Publication bias	Overall certainty of evidence	With placebo	With Intravenous Vitamin C Monotherapy	Relative effect (95% CI)	Risk with placebo	Risk difference with Intravenous Vitamin C Monotherapy
Overall mortality
2130 (16 RCTs)	Serious^a	Serious^b	Not serious	Not serious^c	none	⨁⨁◯◯ Low	365/1028 (35.5%)	321/1102 (29.1%)	RR 0.73 (0.60 to 0.89)	355 per 1,000	96 Fewer per 1000 (from 142 to 39 fewer)

CI confidence interval, MD mean difference, RR risk ratio, SMD standardised mean difference
^a3/16 of the included trials are of low risk of bias, accounting for 30.7% of the weight in random-effect meta-analysis, while 7/16 of the included trials are of high risk of bias, accounting for 40.6% of the weight in random-effect meta-analysis. However, result of the sensitivity analysis using fixed-effect meta-analysis (low risk of bias studies account for 48.5% of the weight) is consistent with the result of random-effect meta-analysis. Therefore, the result is downgraded by one instead of two levels
^bThe overall heterogeneity I² is 42%
^cBoth sensitivity analysis using the fixed-effect model meta-analysis, and the result of trial sequential analysis are similar to the main finding