TABLE 1.
Characteristics of included studies assessing association between enhanced influenza vaccines and risk of influenza‐associated hospitalizations among adults aged ≥65 years (n = 32).
| Study | Location | Season(s) | Vaccine groups (n) | Outcomes | Data source | Funding source |
|---|---|---|---|---|---|---|
| Individually randomized studies (n = 3) | ||||||
| DiazGranados 2015 28 |
United States Canada |
2011–2012 2012–2013 |
HD‐IIV3 (15,990) SD‐IIV3 (15,993) |
Serious events (primarily hospitalizations) adjudicated as probably due to influenza |
RCT | Manufacturer (Sanofi) |
| Vardeny 2021 29 |
United States Canada |
2016–2017 to 2018–2019 |
HD‐IIV3 (2606) SD‐IIV3 (2604) |
Hospitalizations adjudicated as related to influenza or pneumonia | RCT | Government and manufacturer (Sanofi) |
| Johansen 2023 30 | Denmark | 2021–2022 |
HD‐IIV4 (6245) SD‐IIV4 (6232) |
Hospitalizations for pneumonia or influenza (ICD10 J09‐J18) | Danish Health Data Authority | Manufacturer (Sanofi) |
| Cluster‐randomized studies (n = 2) | ||||||
| Gravenstein 2017 31 | United States | 2013–2014 |
HD‐IIV3 (19,127) SD‐IIV3 (19,129) |
Hospitalizations for pneumonia or influenza from Medicare Part A claims (ICD9 460–466, 480–488, 490–496, 500–518) | RCT and US Medicare | Manufacturer (Sanofi) |
| McConeghy 2020 32 | United States | 2016–2017 |
aIIV3 (24,926) SD‐IIV3 (25,286) |
Hospitalizations for pneumonia or influenza from Medicare Part A claims (ICD10 J09‐J18) | RCT and US Medicare | Manufacturer (Seqiris) |
| Cohort studies (n = 12) | ||||||
| Cocchio 2020 35 | Italy |
2011–2012 to 2016–2017 |
aIIV3 (68,660) SD‐IIV4 (410,737) |
Hospitalizations for pneumonia or influenza (ICD9 482.9, 485, 486, 487) a | Italian National Health Service | Government |
| Izurieta 2019 39 | United States | 2017–2018 |
HD‐IIV3 (8,488,136) aIIV3 (1,466,918) SD‐IIV4 (1,822,162) SD‐IIV3 (994,763) |
Hospitalizations for influenza (ICD10 J09, J10, J11, J129) | US Medicare | Government |
| Izurieta 2020 40 | United States | 2018–2019 |
HD‐IIV3 (7,905,252) aIIV3 (2,100,592) SD‐IIV4 (1,454,340) |
Hospitalizations for influenza (ICD10 J09, J10, J11, and J129) | US Medicare | Government |
| Izurieta 2021 17 | United States | 2019–2020 |
HD‐IIV3 (7,173,433) aIIV3 (2,565,513) RIV4 (608,433) SD‐IIV4 (1,584,451) |
Hospitalizations for influenza (ICD10 J09, J10, J11, J129) |
US Medicare | Government |
| Lu 2019 41 , b | United States |
2012–2013 to 2017–2018 |
HD‐IIV3 (10,990,902) SD‐IIV3 (2,449,025) |
Hospitalizations for influenza (ICD10 J09, J10, J11, J129; ICD9 487, 488) | US Medicare | Government |
| Mannino 2012 42 | Italy |
2006–2007 to 2008–2009 |
aIIV3 (84,665) SD‐IIV3 (79,589) |
Hospitalizations for pneumonia or influenza (ICD9 480–487) |
Italian National Health Care System | Manufacturer (Novartis) |
| Paudel 2020 45 | United States |
2011–2012 to 2014–2015 |
HD‐IIV3 (5,737,876) SD‐IIV3 (5,737,876) |
Hospitalizations for pneumonia or influenza (ICD9 codes, any position, not specified) | US Medicare | Manufacturer (Sanofi) |
| Richardson 2015 50 | United States | 2010–2011 |
HD‐IIV3 (25,714) SD‐IIV3 (139,511) |
Hospitalizations for pneumonia or influenza (ICD9 480–487 as primary diagnosis) |
US VHA | Government |
| Robison 2018 51 | United States | 2016–2017 |
HD‐IIV3 (23,712) SD‐IIV3 (23,712) |
Hospitalizations (PCR‐confirmed) |
CDC Influenza Surveillance Network (FluSurvNet) |
Government |
| van Aalst 2020 55 | United States |
2016–2017 to 2017–2018 |
HD‐IIV3 (1,900,920) aIIV3 (223,793) |
Hospitalizations for respiratory illness (ICD10 Jxx, primary discharge diagnosis) | Optum Clinformatics Data Mart c | Manufacturer (Sanofi) |
| Young‐Xu 2018 56 | United States | 2015–2016 |
HD‐IIV3 (49,091) SD‐IIV3 (24,682) |
Hospitalizations for pneumonia or influenza (ICD9 480–488 as a principal or secondary diagnosis) | US VHA | Manufacturer (Sanofi) |
| Young‐Xu 2019 57 | United States |
2010–2011 to 2014–2015 |
HD‐IIV3 (158,636) SD‐IIV3 (3,480,288) person‐seasons |
Hospitalizations for pneumonia or influenza (ICD9 480–488) | US VHA | Manufacturer (Sanofi) |
| Case–control studies (n = 15) | ||||||
| Bella 2019 33 | Italy | 2017–2018 |
aIIV3 (228) No vaccine (252) |
Hospitalizations (PCR‐confirmed) | Government | |
| Cheng 2019 34 | Australia | 2018 |
aIIV3 (NR) HD‐IIV3 (NR) No vaccine (NR) |
Hospitalizations (nucleic acid test‐confirmed) | Government | |
| Doyle 2021 36 | United States |
2015–2016 to 2016–2017 |
HD‐IIV3 (622) SD‐IIV (485) |
Hospitalizations (PCR‐confirmed) | CDC Hospitalized Adult Influenza Vaccine Effectiveness Network | Government |
| Gasparini 2013 37 | Italy | 2010–2011 |
aIIV3 (88) No vaccine (139) |
Hospitalizations for pneumonia or influenza (ICD9 480–487) | University | |
| Grijalva 2021 38 | United States | 2019–2020 |
HD‐IIV3 (142) No vaccine (63) |
Hospitalizations (PCR‐confirmed) | CDC IVY network | Government |
| Mira‐Iglesias 2019 43 | Spain | 2017–2018 |
aIIV3 (339) No vaccine (727) |
Hospitalizations (PCR‐confirmed) | Government and manufacturer (Sanofi) | |
| Mira‐Iglesias 2021 44 | Spain | 2018–2019 |
aIIV3 (305) No vaccine (245) |
Hospitalizations (PCR‐confirmed) | Government and manufacturer (Sanofi) | |
| Pebody 2020 46 | England | 2018–2019 |
aIIV3 (818) SD‐IIV (21) |
Hospitalizations (PCR‐confirmed) | Government | |
| Pott 2023 47 | Canada |
2012–2013 to 2014–2015 |
aIIV3 (526) SD‐IIV3 (3364) |
Hospitalizations (PCR‐confirmed) | Canadian SOS platform | Government and manufacturer (GlaxoSmithKline) |
| Puig‐Barbera 2004 48 | Spain | 2002–2003 |
aIIV3 (486) No vaccine (329) |
Hospitalizations for pneumonia, including for influenza (ICD9 480–487) | Case–control study hospital records | Not reported |
| Puig‐Barbera 2007 49 | Spain | 2004–2005 |
aIIV3 (401) No vaccine (118) |
Hospitalizations for pneumonia, including for influenza (ICD9 480–487) | Case–control study hospital records | Not reported |
| Spadea 2014 52 | Italy |
2010–2011 to 2011–2012 |
aIIV3 (519) SD‐IIV3 (678) No vaccine (1911) |
Hospitalizations for pneumonia or influenza (ICD9 480–487) | Not reported | |
| Stuurman 2021 53 | Finland, Romania, France, Italy, Spain | 2019–2020 |
aIIV3 (432) SD‐IIV3 (11) SD‐IIV4 (312) d No vaccine (791) |
Hospitalizations (PCR‐confirmed) | European DRIVE platform | Government and manufacturer (Sanofi) |
| Stuurman 2023 54 | Iceland, Italy, France, Romania, Spain | 2021–2022 |
aIIV3 (241) aIIV4 (193) HD‐IIV4 (19) SD‐IIV4 (318) e No vaccine (591) |
Hospitalizations (PCR‐confirmed) | European DRIVE platform | Government and manufacturer (Sanofi) |
| Zimmerman 2023 58 | United States |
2018–2019 to 2019–2020 |
RIV4 (3338) SD‐IIV4 (976) |
Hospitalizations (PCR‐confirmed) | EMR and Theradoc database f | Manufacturer (Sanofi) |
Abbreviations: aIIV3, trivalent MF‐59 adjuvanted inactivated influenza vaccine; aIIV4, quadrivalent MF‐59 adjuvanted inactivated influenza vaccine; CPT, Current Procedural Technology; EMR, electronic medical record; ER, emergency room; HD‐IIV3, trivalent high‐dose inactivated influenza vaccine; HD‐IIV4, quadrivalent high‐dose inactivated influenza vaccine; ICD, International Classification of Diseases code; ILI, influenza‐like illness; LCI, laboratory‐confirmed influenza; NR, not reported; P&I, pneumonia and influenza; PCR, polymerase chain reaction; RCT, randomized clinical trial; RIV4, quadrivalent recombinant influenza vaccine; SD‐IIV, standard‐dose inactivated influenza vaccine of combined or unknown valence; SD‐IIV3, trivalent standard‐dose inactivated influenza vaccine; SD‐IIV4, quadrivalent standard‐dose inactivated influenza vaccine; VE, vaccine efficacy/effectiveness; VHA, Veterans' Health Administration.
Cocchio 2020 includes hospital discharge records with ICD‐9‐CM 482.9 for bacterial pneumonia, unspecified; 485 for bronchopneumonia, unspecified organism; 486 for pneumonia, unspecified organism; and 487 for influenza; definition of “hospitalization” not specified.
Sample size for Lu 2019 does not include estimates from the 2017 to 18 influenza season, which were excluded because they are redundant with data reported in Izurieta 2019.
CDM is a database of administrative health claims from members of a large national U.S. managed care company with 17–19 million annually covered members and includes data from both commercial and Medicare Advantage health plans.
SD‐IIV4 from Stuurman 2021 includes Fluarix Tetra, Influvac Tetra, and VaxiGrip Tetra, with reported estimates for each of these vaccines pooled with pairwise fixed effects meta‐analysis to yield one estimate for SD‐IIV4 versus no vaccine.
SD‐IIV4 from Stuurman 2023 includes Fluarix Tetra, Influvac Tetra, and VaxiGrip Tetra from reported sensitivity analysis combining all SD‐IIV4 vaccines (vs no vaccine).
Theradoc® is an infection control software used to identify patients tested at clinician's discretion for influenza.