Summary of findings for the main comparison. Inactivated parenteral influenza vaccine compared to placebo or 'do nothing' for preventing influenza in healthy adults.

Inactivated parenteral influenza vaccine compared to placebo or 'do nothing' for preventing influenza in healthy adults
Patient or population: healthy adults Setting: community‐based studies in North America, South America, and Europe (1969 to 2009) Intervention: inactivated parenteral influenza vaccine Comparison: placebo or 'do nothing'
Outcomes	Anticipated absolute effects* (95% CI)		Relative effect (95% CI)	№ of participants (studies)	Quality of the evidence (GRADE)	Comments
	Risk with placebo or 'do nothing'	Risk with inactivated parenteral influenza vaccine
Influenza assessed by laboratory confirmation Timing of assessment: most studies tested vaccines over a single influenza season	Study population1		RR 0.41 (0.36 to 0.47)	71,221 (25 RCTs)	⊕⊕⊕⊝ MODERATE 2 3
	23 per 1000	9 per 1000 (8 to 11)
Influenza‐like illness assessed by subjective report Timing of assessment: most studies tested vaccines over a single influenza season	Low1		RR 0.84 (0.75 to 0.95)	25,795 (16 RCTs)	⊕⊕⊕⊝ MODERATE 2 4
	40 per 1000	34 per 1000 (30 to 38)
	Moderate
	215 per 1000	181 per 1000 (161 to 205)
	High
	910 per 1000	764 per 1000 (683 to 864)
Hospitalisations Timing of assessment: single influenza season	Study population1		RR 0.96 (0.85 to 1.08)	11,924 (3 RCTs)	⊕⊕⊝⊝ LOW 5 6
	147 per 1000	141 per 1000 (125 to 158)
Time off work Timing of assessment: single influenza season	Study population1		NA	3726 (4 RCTs)	⊕⊕⊝⊝ LOW 7 8
	Average number of days lost per person ranged from 0.2 to 2 days over the season.	Average reduction in working days lost following vaccination was 0.04 days fewer (0.14 fewer to 0.06 days more)
Fever assessed by subjective report Timing of assessment: single influenza season	Study population1		RR 1.55 (1.26 to 1.91)	23,850 (13 RCTs)	⊕⊕⊕⊕ HIGH
	15 per 1000	23 per 1000 (19 to 28)
Nausea or vomiting assessed by subjective report Timing of assessment: single influenza season	Study population1		RR 1.80 (0.65 to 5.04)	6315 (4 RCTs)	⊕⊕⊝⊝ LOW 6 7
	37 per 1000	66 per 1000 (24 to 185)
*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; NA: not applicable; RCT: randomised controlled trial; RR: risk ratio
GRADE Working Group grades of evidence High quality: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate quality: 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 quality: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect. Very low quality: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.

¹Control group risk calculated as the sum of events over total sample size from the control groups. For the outcome of influenza‐like illness, control group risk was stratified as low, moderate (or median), and high due to variation in risk groups across the studies. For the remaining outcomes, the control group risk was taken as aggregate.
 ²Sensitivity analysis by excluding studies with two or more domains at unclear risk of bias did not meaningfully alter the direction, size, or precision of effect. We are confident that bias is unlikely to exaggerate the intervention effect because the absolute reduction in influenza and relative reduction in the risk of influenza‐like illness are small with vaccination.
 ³Downgraded one level due to serious indirectness. Uncertainty over definition, surveillance and testing of influenza in older trials.
 ⁴Downgraded one level for serious inconsistency. There is discordance between the direction and size of effects across the studies. Different definitions of influenza‐like illness across the studies could explain why there is variation in the event rates across the control arms.
 ⁵Downgraded one level due to serious risk of bias. Meta‐analysis heavily influenced by a large study with high risk of bias across several domains.
 ⁶Downgraded one level due to serious imprecision. Confidence interval includes meaningful reduction and increase in effect.
 ⁷Downgraded one level due to serious risk of bias. Effect is influenced by studies judged to be at unclear risk of bias.
 ⁸Downgraded one level due to serious inconsistency. Direction and magnitude of effect differed across the studies (I² = 82%). Wide confidence interval reflects the range of study effect sizes.