Table 4.
GRADE summary of findings table for the critical and important outcomes. Data on immunogenicity considered the Influenza’s vaccine lineage mismatch, and safety considered pooled data, as available within the included reviews
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) |
№ of participants (studies) |
Certainty of the evidence (GRADE) |
Comments | |||
|---|---|---|---|---|---|---|---|---|
| Risk with Trivalent vaccine | Risk with Quadrivalent vaccine | |||||||
| Seroconversion rate (SCR) - Comparison within lineage mismatch (QIV B/Victoria vs. TIV with B/Yamagata OR QIV B/Yamagata vs. TIV with B/Victoria) | ||||||||
| Age: 6 months to 3 years | ||||||||
|
HUANG 2020 QIV B/Victoria vs. TIV with B/Yamagata |
104 per 1,000 |
494 per 1,000 (288 to 848) |
RR 4.74 (2.76 to 8.14) |
2678 (5 RCTs) |
⨁⨁◯◯ Lowb,d |
- | ||
| Age: 3 years to 18 years | ||||||||
|
HUANG 2020 QIV B/Victoria vs. TIV with B/Yamagata |
248 per 1,000 |
768 per 1,000 (494 to 1,000) |
RR 3.09 (1.99 to 4.78) |
6628 (5 RCTs) |
⨁⨁◯◯ Lowb,d |
- | ||
|
HUANG 2020 QIV B/Yamagata vs. TIV with B/Victoria |
355 per 1,000 |
817 per 1,000 (650 to 1,000) |
RR 2.30 (1.83 to 2.88) |
6435 (5 RCTs) |
⨁⨁◯◯ Lowb b,c |
- | ||
| Age: adults (> 18 years and < 65 years) | ||||||||
|
MOA 2016 QIV B/Victoria vs. TIV with B/Yamagata |
383 per 1,000 |
681 per 1,000 (474 to 975) |
RR 1.78 (1.24 to 2.55) |
4342 (4 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
LIANG 2021 QIV B/Victoria vs. TIV with B/Yamagata |
316 per 1,000 |
696 per 1,000 (456 to 1,000) |
RR 2.20 (1.44 to 3.37) |
5291 (7 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
MENG 2018 QIV B/Victoria vs. TIV with B/Yamagata |
385 per 1,000 |
766 per 1,000 (516 to 1,000) |
RR 1.99 (1.34 to 2.97) |
4368 (6 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
MOA 2016 QIV B/Yamagata vs. TIV with B/Victoria |
376 per 1,000 |
793 per 1,000 (568 to 1,000) |
RR 2.11 (1.51 to 2.95) |
4623 (5 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
LIANG 2021 QIV B/Yamagata vs. TIV with B/Victoria |
351 per 1,000 |
660 per 1,000 (537 to 810) |
RR 1.88 (1.53 to 2.31) |
5257 (7 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
MENG 2018 QIV B/Yamagata vs. TIV with B/Victoria |
356 per 1,000 |
690 per 1,000 (533 to 889) |
RR 1.94 (1.50 to 2.50) |
4404 (6 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Seroprotection rate (SPR) – Comparison within lineage mismatch (QIV B/Victoria vs. TIV with B/Yamagata OR QIV B/Yamagata vs. TIV with B/Victoria) | ||||||||
| Age: 6 months to 3 years | ||||||||
|
HUANG 2020 QIV B/Victoria vs. TIV with B/Yamagata |
253 per 1,000 |
611 per 1,000 (360 to 1,000) |
RR 2.41 (1.42 to 4.10) |
988 (3 RCTs) |
⨁⨁◯◯ Low b,c |
- | ||
| Age: 3 years to 18 years | ||||||||
|
HUANG 2020 QIV B/Victoria vs. TIV with B/Yamagata |
636 per 1,000 |
1000 per 1,000 (776 to 1,000) |
RR 1.72 (1.22 to 2.41) |
4895 (4 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
HUANG 2020 QIV B/Yamagata vs. TIV with B/Victoria |
884 per 1,000 |
1000 per 1,000 (911 to 1,000) |
RR 1.16 (1.03 to 1.30) |
4690 (3 RCTs) |
⨁⨁◯◯ Lowb,d |
- | ||
| Age: adults (> 18 years and < 65 years) | ||||||||
|
MOA 2016 QIV B/Victoria vs. TIV with B/Yamagata |
882 per 1,000 |
1000 per 1,000 (909 to 1,000) |
RR 1.14 (1.03 to 1.25) |
4354 (4 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
LIANG 2021 QIV B/Victoria vs. TIV with B/Yamagata |
722 per 1,000 |
967 per 1,000 (794 to 1,000) |
RR 1.34 (1.10 to 1.63) |
5303 (7 RCTs) |
⨁⨁◯◯ Lowb,c |
- | ||
|
MENG 2018 QIV B/Victoria vs. TIV with B/Yamagata |
791 per 1,000 |
1000 per 1,000 (854 to 1,000) |
RR 1.28 (1.08 to 1.51) |
4440 (6 RCTs) |
⨁⨁◯◯ Lowb,c |
- | ||
|
MOA 2016 QIV B/Yamagata vs. TIV with B/Victoria |
907 per 1,000 |
1000 per 1,000 (925 to 1,000) |
RR 1.12 (1.02 to 1.22) |
4634 (5 RCTs) |
⨁⨁◯◯ Lowb,c |
- | ||
|
LIANG 2021 QIV B/Yamagata vs. TIV with B/Victoria |
892 per 1,000 |
990 per 1,000 (919 to 1,000) |
RR 1.11 (1.03 to 1.19) |
5278 (7 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
|
MENG 2018 QIV B/Yamagata vs. TIV with B/Victoria |
903 per 1,000 |
993 per 1,000 (921 to 1,000) |
RR 1.10 (1.02 to 1.18) |
4415 (6 RCTs) |
⨁⨁◯◯ Lowb,c |
- | ||
| Safety: Adverse Events post-vaccination | ||||||||
| Solicited injection site symptoms - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 485 per 1,000 |
441 per 1,000 (354 to 553) |
RR 0.91 (0.73 to 1.14) |
9311 (7 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Solicited general symptoms - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 420 per 1,000 |
462 per 1,000 (390 to 542) |
RR 1.10 (0.93 to 1.29) |
10,094 (6 RCTs) |
⨁⨁◯◯ Lowa,b |
- | ||
| Unsolicited adverse events - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 347 per 1,000 |
358 per 1,000 (326 to 396) |
RR 1.03 (0.94 to 1.14) |
15,714 (8 RCTs) |
⨁⨁◯◯ Lowa,b |
- | ||
| Serious adverse events - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 14 per 1,000 |
13 per 1,000 (9 to 17) |
RR 0.91 (0.67 to 1.23) |
15,925 (9 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Injection site symptoms (pain) - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 430 per 1,000 |
469 per 1,000 (439 to 504) |
RR 1.09 (1.02 to 1.17) |
11,113 (8 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Injection site symptoms (fever) - QIV vs. pooled TIV | ||||||||
| HUANG 2020 | 370 per 1,000 |
392 per 1,000 (344 to 444) |
RR 1.06 (0.93 to 1.20) |
8360 (6 RCTs) |
⨁⨁◯◯ Lowb |
- | ||
| Injection site symptoms (irritability) - QIV vs. pooled | ||||||||
| HUANG 2020 | 370 per 1,000 |
355 per 1,000 (292 to 433) |
RR 0.96 (0.79 to 1.17) |
7998 (5 RCTs) |
⨁⨁◯◯ Lowa,b |
- | ||
| Local adverse events - QIV vs. pooled TIV - adults (> 18 years) | ||||||||
| MOA 2016 | 459 per 1,000 |
533 per 1,000 (441 to 643) |
RR 1.16 (0.96 to 1.40) |
2344 (3 RCTs) |
⨁⨁◯◯ Lowa,b |
- | ||
| Systemic adverse events - QIV vs. pooled TIV - adults (> 18 years) | ||||||||
| MOA 2016 | 351 per 1,000 |
376 per 1,000 (334 to 421) |
RR 1.07 (0.95 to 1.20) |
2344 (3 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Injection site pain - QIV vs. TIV with B/Victoria - adults (> 18 years) | ||||||||
| MOA 2016 | 407 per 1,000 |
464 per 1,000 (379 to 570) |
RR 1.14 (0.93 to 1.40) |
6104 (4 RCTs) |
⨁⨁◯◯ Lowa,b |
- | ||
| Injection site pain - QIV vs. TIV with B/Yamagata - adults (> 18 years) | ||||||||
| MOA 2016 | 356 per 1,000 |
438 per 1,000 (374 to 513) |
RR 1.23 (1.05 to 1.44) |
5502 (3 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Local adverse events - QIV vs. pooled TIV | ||||||||
| LIANG, 2021 | 407 per 1,000 |
452 per 1,000 (407 to 501) |
RR 1.11 (1.00 to 1.23) |
5672 (6 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
| Systemic adverse events - QIV vs. pooled TIV | ||||||||
| LIANG, 2021 | 310 per 1,000 |
325 per 1,000 (300 to 350) |
RR 1.05 (0.97 to 1.13) |
5672 (6 RCTs) |
⨁⨁⨁◯ Moderateb |
- | ||
*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; RR: risk ratio
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. High heterogeneity (I2 > 60% and significant chi-square), with some overlap of the 95% CI, and some differences in the direction of the effect.
b. Did not search gray literature, references or RCT registry sites, did not perform funnel plot.
c. High heterogeneity (I2 > 60% and significant chi-square), with some overlap of the 95% CI.
d. High heterogeneity (I2 > 60% and significant chi-square), with no substantial overlap of the 95% CI.
e. Not all 95% CI overlap at least one point estimate, and some differences in the direction of the effect.