Table 1.

Characteristics of the studies comparing egg-based influenza vaccines and cell culture-based vaccines

Type of study	First author, year of publication [reference]	Number of patients	Primary variable	Age group	Patients included	Effectiveness (percent) (95% CI)
Clinical trial	Frey S, 2010 [16]	11,404	ILI and PCR influenza confirmation	Patients 18-49	United States, Finland, and Poland	rVE versus placebo Cell culture-based trivalent: - 83.8 (61.0, 97.5) against vaccine strains - 69.5 (55.0, 97.5) against circulating strains Egg-based trivalent: - 78.4 (52.1, 97.5) against vaccine strains - 63 (46.7, 97.5) against circulating strains
	Klein NP, 2020 [21]	3,053,248	Influenza confirmed by PCR	Patients aged 4 to 64 years	Kaiser Permanente Members (Northern California, USA)	rVE against A virus (cell culture vs egg) 4-64 years: 8.0 (-10, 23) 4-17 years: 17.8 (-6.2, 36.4) 18-64 years: -5.8 (–36.1, -17.7) rVE against B virus (cell culture vs egg) 4-64 years: 39.6 (27.9, 49.3)a 4-17 years: 42.3 (28.4, 53.5)a 18-64 years: 21.4 (-36.1, 17.7)
	Boikos C, 2020 [22]	1,353,862	Visit to primary care for ILI	Patients older than 4 years	US Primary Care electronic medical records (EMR)	rVE (cell culture vs egg) 18- 64 years: 26.8 (14.1, 37.6) ≥ 65 years: -7.3 (-51.6, 24.0) 4-17 years: 18.8 (-53.9, 57.2)
	DeMarcus L, 2019 [18]	4,037	Influenza confirmed by PCR and/or culture	≥ 6 months	Outpatient records Department of Defense	rVE versus non-vaccinated All ages: - Non-significant differences for H3N2 - H1N1 86 (68, 91) for egg-based 61 (38, 76) for cell culture-based Children (6 months-17 years) - Non-significant differences for H3N2 - H1N1 88 (80, 93) for egg-based 56 (15- 77) for cell culture-based
Retrospective observational study	Bruxvoort KJ, 2019 [20]	8,132	Hospitalization for influenza confirmed by PCR	Patients > 4 years to < 65 Patients > 65 years	Kaiser Permanente Members (California, US)	rVE (cell culture vs egg) < 65 years: 43 (-45, 77) > 65 years: 61 (-63, 91)
	Izurieta HS, 2019 [23]	> 16,000,000	Primary: Hospital records (admissions + emergency)	Patients ≥ 65 years	Medicare members (US)	rVE (cell culture vs egg) vs hospitalizations All ages: - 11 (7.9, 14.0)
	Izurieta HS, 2020 [24]	12,777,214	Primary: Hospital records (admissions + emergency)	Patients ≥ 65 years	Medicare members (US)	rVE (cell culture vs egg) vs hospitalizations All ages vs hospital events: - 0.8 (-4.6, 5.9.) All ages vs hospitalizations - 3.4 (-3.6, 9.8)
	Izurieta HS, 2020, [25]	12,700,000	Primary: Hospital records (admissions + emergency)	Patients ≥ 65 years	Medicare members (US)	rVE (cell culture vs egg) vs hospitalizations All ages vs hospital events: - 2.8 (-2.8, 8.2)

^ap < 0.0001; rVE: relative vaccine effectiveness; CI: confidence interval