Characteristics of included studies (n=18)
| Study ID, first author, year | Influenza season | Country/ region | N randomised | Included in the overall safety set* | Vaccines (route of administration)¶ | Females | Median age (range)/ age groups (in years)** | Risk of bias (ROBINS-I) |
| N (%) | ||||||||
| 41 501 | 34 343 (82.8%) | N (%) | ||||||
| Sanofi Pasteur | ||||||||
| GQM01 Pepin, 201335 | NH 2011–2012 | Western or Eastern Europe | 1568 | 1565 (99.8%) | IIV4/IIV3 (IM) | 916 (58.4%) | F: 59 y (18–89) M: 62 y (18–91) | Serious |
| GQM04 Cadorna-Carlos, 201536 | NH 2011–2012 | Australia, Philippines | 1566 | 1565 (99.8%) | IIV4/IIV3 (IM) | 918 (58.6%) | F: 23–36 y, N=306 F: >36–47 y, N=306 F: >47–61 y, N=306 M: 19–28 y, N=216 M: >28–44 y, N=216 M: >44–61 y, N=216 | Serious |
| GQM07 Choi, 2017 | NH 2015–2016 | Korea | 300 | 300 (100.0%) | IIV4/IIV3 (IM) | 221 (73.7%) | F: 36 y (20–60) M: 34 y (19–60) | Serious |
| GQM11 Sesay, 201838 | NH 2014–2015 | Western or Eastern Europe | 2225 | 2222 (99.9%) | IIV4/IIV3 (IM) | 1204 (54.1%) | F: 58 y (18–91) M: 62 y (18–88) | Serious |
| QID01 Gorse, 201531 | NH 2012–2013 | USA | 3360 | 3355 (99.9%) | QIV/TIV (ID) | 2059 (61.3%) | F: 18–49 y, N=1345 F: 50–64 y, N=710 M: 18–49 y, N=888 M: 50–64 y, N=412 | Low |
| QIV03 Not published | NH 2010–2011 | USA | 739 | 739 (100.0%) | IIV4/IIV3 (IM) | 403 (54.5%) | F: 71 y (30–92) M: 71 y (18–95) | Serious |
| QIV06 Not published | SH 2015 | India | 100 | 100 (100.0%) | IIV4 (IM) | 34 (34.0%) | F: 18–64 y, N=22 F: 65 y+, N=12 M: 18–64 y, N=48 M: 65 y+, N=18 | Serious |
| RPV03C Not published | NH 2010–2011 | France, Germany | 954 | 472 (49.5%†) | IIV3/REPEVAX (IM) | 537 (56.3%) | F: 67 y (60–92) M: 67 y (60–88) | Serious |
| GlaxoSmithKline | ||||||||
| 112 963 Tinico, 2014 | NH 2010–2011 | USA, Mexico, Canada | 1707 | 1703 (99.8%) | IIV4/IIV3 (IM) | 1046 (61.3%) | F: 49 y (18–89) M: 53 y (18–88) | Low |
| 201 251 Claeys, 201840 | NH 2014–2015 | Germany | 120 | 120 (100.0%) | IIV4 (IM) | 76 (63.3%) | F: 28 y (19–49) M: 29 y (18–49) | Low |
| 114 269 Kieninger, 201341 | NH 2010–2011 | USA, Korea, Germany, Romania, Spain, Taiwan | 4659 | 4656 (99.9%) | IIV4/IIV3 (IM) | 2638 (56.6%) | F: 62 y (18–89) M: 66 y (18–89) | Low |
| 117 036 Schwarz, 201742 | NH 2013–2014 | USA, Germany, Canada | 829 | 415 (50.0%‡) | IIV4/HZ/su (IM) | 429 (51.8%) | F: 63 y (50–87) M: 61 y (50–88) | Low |
| CSL Seqirus | ||||||||
| CSLCT-QIV-13–01 Treanor, 201743 | NH 2014–2015 | USA | 3484 | 3449 (99.0%) | IIV4/IIV3 (IM) | 1992 (57.8%) | F: 18–49 y, N=612 F: 50–64 y, N=406 F: 65 y+, N=974 M: 18–49 y, N=408 M: 50–64 y, N=315 M: 65 y+, N=869 | Low |
| V118-18 Not published | NH 2016–2017, SH 2017 | Bulgaria, Colombia, Czech Republic, Estonia, Latvia, Lithuania, Malaysia, Philippines, Poland, Romania, Thailand, Turkey | 6790 | 665 (9.8%§) | aQIV/Boostrix (IM) | 2089 (61.5%) | F: 65 y+, N=4194 M: 65 y+, N=2596 | Low |
| V58-23 Not published | NH 2014–2015 | USA | 1560 | 1560 (100.0%) | TIVc/TIVf (IM) | 940 (60.3%) | F: 18–49 y, N=940 M: 18–49 y, N=620 | Low |
| V70-27 Frey, 201444 | NH 2010–2011 | USA | 7082 | 7019 (99.0%) | aTIV/TIV (IM) | 4554 (64.3%) | F: 65 y+, N=4616 M: 65 y+, N=2468 | Low |
| V118-20 Beran, 202145 | NH 2017–2018 | USA | 1778 | 1776 (99.9%) | aQIV/aTIV (IM) | 1007 (56.6%) | F: 65 y+, N=1007 M: 65 y+, N=771 | Low |
| V130-01 Bart, 201630 | NH 2013–2014 | USA | 2680 | 2662 (99.3%) | QIVc/TIVc (IM) | 1516 (56.6%) | F: 18–49 y, N=495 F: 50–64 y, N=272 F: 65 y+, N=749 M: 18–49 y, N=368 M: 50–64 y, N=205 M: 65 y+, N=591 | Low |
*Corresponds to participants who received one of the study vaccines (total vaccinated cohort for analysis of safety). The number of participants with solicited data available may vary.
†Only data from group 2 (influenza vaccine alone at visit 1 followed by REPEVAX at visit 2) post visit 1 were used for the safety evaluation. Data for solicited reactions were not available.
‡Only data from the control group (influenza vaccine alone at visit 1 followed by HZ/su vaccine at month 2 and at month 4) post visit 1 were used for the safety evaluation, except for injection site reactions for which we used reactions related to influenza vaccine for each group (ie, the co-administration group: Influenza+HZ/su vaccine at visit 1 followed by HZ/su vaccine at month 2 and the control group).
§Solicited safety set included a randomly selected sample of subjects (subset) and we included only data for influenza vaccine in our analysis.
¶IIV4: quadrivalent split-virion inactivated influenza vaccine (egg-derived). IIV3: trivalent split-virion inactivated influenza vaccines (egg-derived). QIV ID: quadrivalent influenza intradermal vaccine (zonal purified subvirion). TIV ID: trivalent influenza intradermal vaccine (zonal purified subvirion). REPEVAX: diphtheria, tetanus, pertussis (acellular, component) and poliomyelitis (inactivated) vaccine. HZ/su: adjuvanted herpes zoster subunit vaccine. PPV23: 23-valent pneumococcal polysaccharide vaccine. aQIV: adjuvanted quadrivalent influenza vaccine (egg-derived). Boostrix: diphtheria, tetanus and pertussis (acellular, component). TIVc: cell-derived trivalent influenza vaccine. TIVf: egg-derived trivalent influenza vaccine. aTIV: adjuvanted trivalent vaccine (egg-derived). QIVc: cell-derived trivalent influenza vaccine.
**According to anonymisation standards, data on age were only available in quartiles for females and males for Sanofi’s studies. For GlaxoSmithKline’s studies, subject age was set to blank over 89 y. For Seqirus’s studies, data were available by age groups (aggregated).
F, females; ID, intradermal; IM, intramuscular; M, males; NA, not available; NH, Northern hemisphere; QIV, quadrivalent vaccine; ROBINS-I, Risk of Bias in Non-Randomized Studies of Interventions ; SH, Southern hemisphere; TIV, trivalent vaccine ; y, years.