Scolaris Content Display Scolaris Content Display

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Comparison 1 Live vaccine versus placebo or no intervention (RCTs by age group), Outcome 1 Influenza.
Figures and Tables -
Analysis 1.1

Comparison 1 Live vaccine versus placebo or no intervention (RCTs by age group), Outcome 1 Influenza.

Comparison 1 Live vaccine versus placebo or no intervention (RCTs by age group), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 1.2

Comparison 1 Live vaccine versus placebo or no intervention (RCTs by age group), Outcome 2 Influenza‐like illness.

Comparison 2 Inactivated vaccine versus placebo or no intervention (RCTs by age group), Outcome 1 Influenza.
Figures and Tables -
Analysis 2.1

Comparison 2 Inactivated vaccine versus placebo or no intervention (RCTs by age group), Outcome 1 Influenza.

Comparison 2 Inactivated vaccine versus placebo or no intervention (RCTs by age group), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 2.2

Comparison 2 Inactivated vaccine versus placebo or no intervention (RCTs by age group), Outcome 2 Influenza‐like illness.

Comparison 3 Live attenuated vaccines (cohort studies by age group), Outcome 1 Influenza.
Figures and Tables -
Analysis 3.1

Comparison 3 Live attenuated vaccines (cohort studies by age group), Outcome 1 Influenza.

Comparison 3 Live attenuated vaccines (cohort studies by age group), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 3.2

Comparison 3 Live attenuated vaccines (cohort studies by age group), Outcome 2 Influenza‐like illness.

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 1 Influenza.
Figures and Tables -
Analysis 4.1

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 1 Influenza.

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 4.2

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 2 Influenza‐like illness.

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 3 Otitis media.
Figures and Tables -
Analysis 4.3

Comparison 4 Inactivated vaccines (cohort studies by age group), Outcome 3 Otitis media.

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 1 Influenza.
Figures and Tables -
Analysis 5.1

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 1 Influenza.

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 5.2

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 2 Influenza‐like illness.

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 3 Otitis media (all episodes).
Figures and Tables -
Analysis 5.3

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 3 Otitis media (all episodes).

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 4 Working days lost (number of events, parents).
Figures and Tables -
Analysis 5.4

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 4 Working days lost (number of events, parents).

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 5 Drug prescriptions (number of events).
Figures and Tables -
Analysis 5.5

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 5 Drug prescriptions (number of events).

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 6 Outpatients attendance for pneumonia and influenza.
Figures and Tables -
Analysis 5.6

Comparison 5 Live vaccine versus placebo (RCTs), Outcome 6 Outpatients attendance for pneumonia and influenza.

Comparison 6 Inactivated vaccine versus placebo (RCTs), Outcome 1 Influenza.
Figures and Tables -
Analysis 6.1

Comparison 6 Inactivated vaccine versus placebo (RCTs), Outcome 1 Influenza.

Comparison 6 Inactivated vaccine versus placebo (RCTs), Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 6.2

Comparison 6 Inactivated vaccine versus placebo (RCTs), Outcome 2 Influenza‐like illness.

Comparison 7 Case‐control studies, Outcome 1 Influenza vs influenza‐like illness (crude data).
Figures and Tables -
Analysis 7.1

Comparison 7 Case‐control studies, Outcome 1 Influenza vs influenza‐like illness (crude data).

Comparison 7 Case‐control studies, Outcome 2 Influenza vs influenza‐like illness (adj. estimates).
Figures and Tables -
Analysis 7.2

Comparison 7 Case‐control studies, Outcome 2 Influenza vs influenza‐like illness (adj. estimates).

Comparison 7 Case‐control studies, Outcome 3 Influenza‐like illness vs no symptoms.
Figures and Tables -
Analysis 7.3

Comparison 7 Case‐control studies, Outcome 3 Influenza‐like illness vs no symptoms.

Comparison 8 Vaccine versus placebo, Outcome 1 Influenza.
Figures and Tables -
Analysis 8.1

Comparison 8 Vaccine versus placebo, Outcome 1 Influenza.

Comparison 8 Vaccine versus placebo, Outcome 2 Influenza‐like illness.
Figures and Tables -
Analysis 8.2

Comparison 8 Vaccine versus placebo, Outcome 2 Influenza‐like illness.

Comparison 8 Vaccine versus placebo, Outcome 3 Secondary cases.
Figures and Tables -
Analysis 8.3

Comparison 8 Vaccine versus placebo, Outcome 3 Secondary cases.

Comparison 8 Vaccine versus placebo, Outcome 4 School absenteeism.
Figures and Tables -
Analysis 8.4

Comparison 8 Vaccine versus placebo, Outcome 4 School absenteeism.

Comparison 8 Vaccine versus placebo, Outcome 5 Lower respiratory tract disease.
Figures and Tables -
Analysis 8.5

Comparison 8 Vaccine versus placebo, Outcome 5 Lower respiratory tract disease.

Comparison 8 Vaccine versus placebo, Outcome 6 Acute otitis media.
Figures and Tables -
Analysis 8.6

Comparison 8 Vaccine versus placebo, Outcome 6 Acute otitis media.

Comparison 8 Vaccine versus placebo, Outcome 7 Hospitalisation due to acute otitis media.
Figures and Tables -
Analysis 8.7

Comparison 8 Vaccine versus placebo, Outcome 7 Hospitalisation due to acute otitis media.

Comparison 8 Vaccine versus placebo, Outcome 8 Consequences of acute otitis media.
Figures and Tables -
Analysis 8.8

Comparison 8 Vaccine versus placebo, Outcome 8 Consequences of acute otitis media.

Comparison 8 Vaccine versus placebo, Outcome 9 Outpatients attendance for pneumonia and influenza.
Figures and Tables -
Analysis 8.9

Comparison 8 Vaccine versus placebo, Outcome 9 Outpatients attendance for pneumonia and influenza.

Comparison 8 Vaccine versus placebo, Outcome 10 Working days lost (number of events, parents of children 6‐36 months of age).
Figures and Tables -
Analysis 8.10

Comparison 8 Vaccine versus placebo, Outcome 10 Working days lost (number of events, parents of children 6‐36 months of age).

Comparison 8 Vaccine versus placebo, Outcome 11 Drug prescriptions (number of events, 6‐36 months of age).
Figures and Tables -
Analysis 8.11

Comparison 8 Vaccine versus placebo, Outcome 11 Drug prescriptions (number of events, 6‐36 months of age).

Table 1. Sensitivity analysis

Comparison

Vaccine type

Study type

Outcome

Age group

Without Russian studies

Datasets

All studies

Datasets

Risk ratio (random) (95% CI)

Risk ratio (random) (95% CI)

01.01

Live

RCTs

Influenza

</= 2 years

</= 6 years

0.15 (0.10 to 0.23)

5

0.15 (0.10 to 0.23)

5

> 6 years

0.47 (0.23 to 0.97)

1

0.47 (0.23 to 0.97)

1

Total

0.18 (0.11 to 0.29)

6

0.18 (0.11 to 0.29)

6

01.02

Live

RCTs

ILI

</= 2 years

</= 6 years

0.54 (0.12 to 2.42)*

1

0.67 (0.57 to 0.77)

5

> 6 years

0.12 (0.01 to 2.11)*

1

0.67 (0.60 to 0.74)

8

Total

0.39 (0.10 to 1.48)*

2

0.67 (0.62 to 0.72)

13

02.01

Inactivated

RCTs

Influenza

</= 2 years

0.55 (0.18 to 1.69)

2

0.55 (0.18 to 1.69)

2

</= 6 years

0.61 (0.34 to 1.08)

2

0.61 (0.34 to 1.08)

2

> 6 years

0.31 (0.22 to 0.45)

3

0.31 (0.22 to 0.45)

3

Total

0.41 (0.29 to 0.59)

7

0.41 (0.29 to 0.59)

7

02.02

Inactivated

RCTs

ILI

</= 2 years

</= 6 years

0.39 (0.21 to 0.69)

3

0.39 (0.21 to 0.69)

3

> 6 years

0.24 (0.08 to 0.70)+

2

0.72 (0.66 to 0.78)

4

Total

0.34 (0.24 to 0.50)+

5

0.64 (0.54 to 0.76)

7

03.01

Live

Cohort studies

Influenza

</= 2 years

</= 6 years

> 6 years

0.56 (0.35 to 0.91)

1

Total

No studies

0.56 (0.35 to 0.91)

1

03.02

Live

Cohort studies

ILI

</= 2 years

</= 6 years

> 6 years

0.63 (0.57 to 0.69)

1

0.63 (0.57 to 0.69)

2

Total

0.63 (0.57 to 0.69)

1

0.63 (0.57 to 0.69)

2

04.01

Inactivated

Cohort studies

Influenza

</= 2 years

0.63 (0.27 to 1.47)

3

0.63 (0.27 to 1.47)

3

</= 6 years

0.34 (0.13 to 0.89)

1

0.34 (0.13 to 0.89)

1

> 6 years

0.20 (0.10 to 0.39)*

1

0.36 (0.12 to 1.11)

2

Total

0.36 (0.19 to 0.66)

5

0.42 (0.25 to 0.73)

6

04.02

Inactivated

Cohort studies

ILI

</= 2 years

</= 6 years

0.40 (0.13 to 1.20)

3

0.81 (0.65 to 1.01)

4

> 6 years

0.10 (0.05 to 0.21)+

1

0.44 (0.29 to 0.68)

7

Total

0.26 (0.07 to 0.92)+

4

0.55 (0.42 to 0.70)

11

ILI: Influenza‐like illness
RCTs: randomised controlled trials
*: significance change
+: possible decision‐making significant change

Figures and Tables -
Table 1. Sensitivity analysis
Table 2. Risk of bias sensitivity analysis

All datasets

Excluding studies with high risk of bias

Comparisons

Effect measure

Number of datasets

Effect estimate

LL 95% CI

UL 95% CI

Statistical significance

Number of datasets

Effect estimate*

LL 95% CI

UL 95% CI

Statistical significance

VE absolute change

Change effect measure direction

Change in statistical significance

Analysis 1.1

Influenza

Risk ratio

7

0.20

0.13

0.32

Sign

5

0.23

0.12

0.49

Sign

‐3%

Unchanged

Unchanged

Analysis 1.1.1

Under 2 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 1.1.2

Under 6 years

Risk ratio

6

0.18

0.11

0.29

Sign

4

0.20

0.10

0.42

Sign

‐2%

Unchanged

Unchanged

Analysis 1.1.3

Over 6 years

Risk ratio

1

0.47

0.23

0.97

Sign

1

0.47

0.23

0.97

Sign

0%

Unchanged

Unchanged

Analysis 1.2

Influenza‐like illness

Risk ratio

13

0.67

0.62

0.72

Sign

5

0.5

0.45

0.55

Sign

17%

Unchanged

Unchanged

Analysis 1.2.1

Under 2 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 1.2.2

Under 6 years

Risk ratio

5

0.67

0.57

0.77

Sign

2

0.48

0.44

0.54

Sign

19%

Unchanged

Unchanged

Analysis 1.2.3

Over 6 years

Risk ratio

8

0.67

0.6

0.74

Sign

3

0.55

0.4

0.76

Sign

12%

Unchanged

Unchanged

Analysis 2.1

Influenza

Risk ratio

7

0.41

0.29

0.59

Sign

7

0.41

0.29

0.59

Sign

0%

Unchanged

Unchanged

Analysis 2.1.1

Under 2 years

Risk ratio

2

0.55

0.18

1.69

No sign

2

0.55

0.18

1.69

No sign

0%

Unchanged

Unchanged

Analysis 2.1.2

Under 6 years

Risk ratio

2

0.61

0.34

1.08

No Sign

2

0.61

0.34

1.08

No Sign

0%

Unchanged

Unchanged

Analysis 2.1.3

Over 6 years

Risk ratio

3

0.31

0.22

0.45

Sign

3

0.31

0.22

0.45

Sign

0%

Unchanged

Unchanged

Analysis 2.2

Influenza‐like illness

Risk ratio

7

0.64

0.54

0.76

Sign

4

0.39

0.19

0.8

Sign

25%

Unchanged

Unchanged

Analysis 2.2.1

Under 2 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 2.2.2

Under 6 years

Risk ratio

3

0.39

0.21

0.69

Sign

2

0.52

0.14

1.98

No sign

‐13%

Unchanged

Changed

Analysis 2.2.3

Over 6 years

Risk ratio

4

0.72

0.66

0.78

Sign

2

0.24

0.08

0.7

Sign

48%

Unchanged

Unchanged

Analysis 3.1

Influenza

Risk ratio

1

0.56

0.35

0.91

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 3.1.1

Under 2 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 3.1.2

Under 6 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 3.1.3

Over 6 years

Risk ratio

1

0.56

0.35

0.91

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 3.2

Influenza‐like illness

Risk ratio

2

0.63

0.57

0.69

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 3.2.1

Under 2 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 3.2.2

Under 6 years

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 3.2.3

Over 6 years

Risk ratio

2

0.63

0.57

0.69

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.1

Influenza

Risk ratio

6

0.42

0.25

0.73

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.1.1

Under 2 years

Risk ratio

3

0.63

0.27

1.47

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.1.2

Under 6 years

Risk ratio

1

0.34

0.13

0.89

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.1.3

Over 6 years

Risk ratio

2

0.36

0.12

1.11

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.2

Influenza‐like illness

Risk ratio

13

0.53

0.42

0.67

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.2.1

Under 2 years

Risk ratio

1

0.47

0.23

0.93

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.2.2

Under 6 years

Risk ratio

5

0.74

0.59

0.93

Sign

1

0.98

0.94

1.03

No sign

‐24%

Unchanged

Changed

Analysis 4.2.3

Over 6 years

Risk ratio

7

0.44

0.29

0.68

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.3

Otitis media

Risk ratio

1

0.48

0.22

1.03

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 4.3.1

Children aged 6 months to 5 years

Risk ratio

1

0.48

0.22

1.03

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 5.1

Influenza

Risk ratio

7

0.19

0.11

0.32

Sign

5

0.21

0.09

0.48

Sign

‐2%

Unchanged

Unchanged

Analysis 5.1.1

Live attenuated vaccines (1 dose)

Risk ratio

5

0.23

0.12

0.47

Sign

3

0.38

0.2

0.75

Sign

‐11%

Unchanged

Unchanged

Analysis 5.1.2

Live attenuated vaccines (2 doses)

Risk ratio

2

0.11

0.04

0.26

Sign

2

0.11

0.04

0.26

Sign

0%

Unchanged

Unchanged

Analysis 5.2

Influenza‐like illness

Risk ratio

8

0.69

0.6

0.8

Sign

3

0.53

0.39

0.74

Sign

16%

Unchanged

Unchanged

Analysis 5.2.1

Live attenuated vaccines (1 dose)

Risk ratio

2

0.64

0.18

2.22

No sign

1

0.27

0.06

1.16

No sign

37%

Unchanged

Unchanged

Analysis 5.2.2

Live attenuated vaccines (2 doses)

Risk ratio

6

0.66

0.57

0.76

Sign

2

0.55

0.39

0.79

Sign

11%

Unchanged

Unchanged

Analysis 5.3

Otitis media (all episodes)

Risk ratio

2

0.98

0.95

1.01

No sign

1

0.98

0.95

1.01

No sign

0%

Unchanged

Unchanged

Analysis 5.4

Working days lost (number of events, parents)

Risk ratio

2

0.69

0.46

1.03

No sign

2

0.69

0.46

1.03

No sign

0%

Unchanged

Unchanged

Analysis 5.5

Drug prescriptions (number of events)

Risk ratio

1

0.99

0.87

1.12

No sign

1

0.99

0.87

1.12

No sign

0%

Unchanged

Unchanged

Analysis 5.6

Outpatients attendance for pneumonia and influenza

Risk ratio

2

0.76

0.59

0.98

Sign

2

0.76

0.59

0.98

Sign

0%

Unchanged

Unchanged

Analysis 6.1

Influenza

Risk ratio

5

0.36

0.28

0.48

Sign

5

0.36

0.28

0.48

Sign

0%

Unchanged

Unchanged

Analysis 6.1.1

Inactivated vaccines (1 dose)

Risk ratio

5

0.36

0.28

0.48

Sign

5

0.36

0.28

0.48

Sign

0%

Unchanged

Unchanged

Analysis 6.1.2

Inactivated vaccines ( 2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 6.2

Influenza‐like illness

Risk ratio

4

0.72

0.65

0.79

Sign

2

0.35

0.15

0.81

Sign

37%

Unchanged

Unchanged

Analysis 6.2.1

Inactivated vaccines (1 dose)

Risk ratio

2

0.35

0.15

0.81

Sign

2

0.35

0.15

0.81

Sign

0%

Unchanged

Unchanged

Analysis 6.2.2

Inactivated vaccines (2 doses)

Risk ratio

2

0.72

0.69

0.76

Sign

0

0

0

0

‐‐

Unchanged

changed

Analysis 7.1

Influenza vs ILI (crude data)

Odds Ratio

 

‐‐

 

‐‐

Unchanged

Unchanged

Analysis 7.1.1

Children aged below 6 years

Odds Ratio

9

0.59

0.45

0.77

Sign

6

0.55

0.44

0.7

Sign

4%

Unchanged

Unchanged

Analysis 7.1.2

Children aged 5 to 19 years

Odds Ratio

1

0.76

0.07

8.66

No sign

1

0.76

0.07

8.66

No sign

0%

Unchanged

Unchanged

Analysis 7.2

Influenza vs ILI (adj. estimates)

Odds Ratio

 

‐‐

 

‐‐

Unchanged

Unchanged

Analysis 7.2.1

Children aged below 23 months to fully vaccinated

Odds Ratio

7

0.6

0.39

0.94

Sign

4

0.46

0.29

0.73

Sign

14%

Unchanged

Unchanged

Analysis 7.2.2

Children aged 24 to 59 months to fully vaccinated

Odds Ratio

4

0.4

0.22

0.7

Sign

4

0.4

0.22

0.7

Sign

0%

Unchanged

Unchanged

Analysis 7.2.3

Children aged 6 to 59 months to fully vaccinated

Odds Ratio

5

0.45

0.32

0.62

Sign

5

0.45

0.32

0.62

Sign

0%

Unchanged

Unchanged

Analysis 7.2.4

Children aged below 14 years old to fully vaccinated

Odds Ratio

1

0.23

0.06

0.84

Sign

1

0.23

0.06

0.84

Sign

0%

Unchanged

Unchanged

Analysis 7.3

Influenza‐like illness vs no symptoms

Odds Ratio

2

0.49

0.28

0.86

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 7.3.1

Inactivated vaccine (1 dose)

Odds Ratio

1

0.53

0.26

1.07

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 7.3.2

Inactivated vaccine (2 doses)

Odds Ratio

1

0.44

0.18

1.1

No sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 8.1

Influenza

Risk ratio

11

0.27

0.18

0.42

Sign

11

0.27

0.18

0.42

Sign

0%

Unchanged

Unchanged

Analysis 8.1.1

Live attenuated vaccines (1 dose)

Risk ratio

4

0.27

0.12

0.61

Sign

4

0.27

0.12

0.61

Sign

0%

Unchanged

Unchanged

Analysis 8.1.2

Live attenuated vaccines (2 doses)

Risk ratio

2

0.11

0.04

0.26

Sign

2

0.11

0.04

0.26

Sign

0%

Unchanged

Unchanged

Analysis 8.1.3

Inactivated vaccines (1 dose)

Risk ratio

5

0.36

0.28

0.48

Sign

5

0.36

0.28

0.48

Sign

0%

Unchanged

Unchanged

Analysis 8.1.4

Inactivated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.2

Influenza‐like illness

Risk ratio

12

0.69

0.62

0.77

Sign

5

0.5

0.38

0.67

Sign

19%

Unchanged

Unchanged

Analysis 8.2.1

Live attenuated vaccines (1 dose)

Risk ratio

2

0.64

0.18

2.22

No sign

1

0.27

0.06

1.16

No sign

37%

Unchanged

Unchanged

Analysis 8.2.2

Live attenuated vaccines (2 doses)

Risk ratio

6

0.66

0.57

0.76

Sign

2

0.55

0.39

0.79

Sign

11%

Unchanged

Unchanged

Analysis 8.2.3

Inactivated vaccines (1 dose)

Risk ratio

2

0.35

0.15

0.81

Sign

2

0.35

0.15

0.81

Sign

0%

Unchanged

Unchanged

Analysis 8.2.4

Inactivated vaccines (2 doses)

Risk ratio

2

0.72

0.69

0.76

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 8.3

Secondary cases

Risk ratio

1

1.68

0.56

4.99

No sign

1

1.68

0.56

4.99

No sign

0%

Unchanged

Unchanged

Analysis 8.3.1

Live attenuated vaccines (1 dose)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.3.2

Live attenuated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.3.3

Inactivated vaccines (1 dose)

Risk ratio

1

1.68

0.56

4.99

No sign

1

1.68

0.56

4.99

No sign

0%

Unchanged

Unchanged

Analysis 8.3.4

Inactivated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.4

School absenteeism

Risk ratio

2

0.49

0.26

0.92

Sign

2

0.49

0.26

0.92

Sign

0%

Unchanged

Unchanged

Analysis 8.4.1

Live attenuated vaccines (1 dose)

Risk ratio

1

0.51

0.22

1.19

No sign

1

0.51

0.22

1.19

No sign

0%

Unchanged

Unchanged

Analysis 8.4.2

Live attenuated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.4.3

Inactivated vaccines (1 dose)

Risk ratio

1

0.46

0.17

1.22

No sign

1

0.46

0.17

1.22

No sign

0%

Unchanged

Unchanged

Analysis 8.4.4

Inactivated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.5

Lower respiratory tract disease

Risk ratio

3

0.2

0.03

1.54

No sign

2

0.52

0.08

3.37

No sign

‐32%

Unchanged

Unchanged

Analysis 8.5.1

Live attenuated vaccines (1 dose)

Risk ratio

2

0.16

0.01

4.45

No sign

1

0.73

0.07

7.88

No sign

‐57%

Unchanged

Unchanged

Analysis 8.5.2

Live attenuated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.5.3

Inactivated vaccines (1 dose)

Risk ratio

1

0.3

0.01

6.17

No sign

1

0.3

0.01

6.17

No sign

0%

Unchanged

Unchanged

Analysis 8.5.4

Inactivated vaccines (2 doses)

Risk ratio

0

0

0

0

‐‐

0

0

0

0

‐‐

Unchanged

Unchanged

Analysis 8.6

Acute otitis media

Risk ratio

7

1

0.79

1.26

No sign

5

1.03

0.91

1.17

No sign

‐3%

changed

Unchanged

Analysis 8.6.1

Live attenuated vaccines (1 dose)

Risk ratio

3

0.42

0.05

3.79

No sign

1

1.46

0.09

22.93

No sign

‐104%

changed

Unchanged

Analysis 8.6.2

Live attenuated vaccines (2 doses)

Risk ratio

1

0.98

0.95

1.01

No sign

1

0.98

0.95

1.01

No sign

0%

Unchanged

Unchanged

Analysis 8.6.3

Inactivated vaccines (1 dose)

Risk ratio

1

1.52

0.1

23.76

No sign

1

1.52

0.1

23.76

No sign

0%

Unchanged

Unchanged

Analysis 8.6.4

Inactivated vaccines (2 doses)

Risk ratio

2

1.15

0.95

1.4

No sign

2

1.15

0.95

1.4

No sign

0%

Unchanged

Unchanged

Analysis 8.7

Hospitalisation due to acute otitis media

Risk ratio

 

‐‐

 

‐‐

Unchanged

Unchanged

Analysis 8.7.1

Inactivated vaccine (2 doses)

Risk ratio

2

1.41

0.62

3.24

No sign

2

1.41

0.62

3.24

No sign

0%

Unchanged

Unchanged

Analysis 8.8

Consequences of acute otitis media

Mean Difference

 

‐‐

 

‐‐

Unchanged

Unchanged

Analysis 8.8.1

Inactivated vaccine, 2 doses visits

Mean Difference

2

‐0.02

‐0.27

0.23

No sign

2

‐0.02

‐0.27

0.23

No sign

Unchanged

Unchanged

Analysis 8.8.2

Inactivated vaccine (2 doses; courses of antibiotics

Mean Difference

2

0.13

‐0.36

0.63

No sign

2

0.13

‐0.36

0.63

No sign

Unchanged

Unchanged

Analysis 8.9

Outpatients attendance for pneumonia and influenza

Risk ratio

2

0.76

0.59

0.98

Sign

1

0.85

0.75

0.96

Sign

‐9%

Unchanged

Unchanged

Analysis 8.9.1

Live attenuated vaccine (1 dose)

Risk ratio

1

0.65

0.49

0.85

Sign

0

0

0

0

‐‐

Unchanged

Changed

Analysis 8.9.2

Live attenuated vaccine (2 doses)

Risk ratio

1

0.85

0.75

0.96

Sign

1

0.85

0.75

0.96

Sign

0%

Unchanged

Unchanged

Analysis 8.10

Working days lost (number of events, parents of children 6 to 36 months of age)

Risk ratio

2

0.69

0.46

1.03

No sign

1

0.83

0.71

0.98

Sign

‐14%

Unchanged

Changed

Analysis 8.10.1

Live attenuated vaccine

Risk ratio

2

0.69

0.46

1.03

No sign

1

0.83

0.71

0.98

Sign

‐14%

Unchanged

Changed

Analysis 8.11

Drug prescriptions (number of events, 6 to 36 months of age)

Risk ratio

1

0.99

0.87

1.12

No sign

1

0.99

0.87

1.12

No sign

0%

Unchanged

Unchanged

Analysis 8.11.1

Live attenuated vaccine

Risk ratio

1

0.99

0.87

1.12

No sign

1

0.99

0.87

1.12

No sign

0%

Unchanged

Unchanged

CI: confidence interval
LL: lower limit
No sign: when effect measure is not statistically significant
risk ratio*: effect estimate excluding high risk of bias datasets
Sign: when effect measure is statistically significant
UL: upper limit
VE absolute change = (1‐RR*)‐(1‐RR)

Figures and Tables -
Table 2. Risk of bias sensitivity analysis
Table 3. Efficacy and effectiveness data from intraepidemic and non‐typical studies

Study reference

Exclusion reason

RCT/Cohort

Vaccine

Age group

Outcome

n treatment

N treatment

n control

N control

Nicholls 2004

Cohort from community not representative of local population

Cohort

Inactive, trivalent

0 to 2 years

ILI

11

18

3

5

Nicholls 2004

Cohort from community not representative of local population

Cohort

Inactive, trivalent

3 to 4 years

ILI

10

16

0

0

Nicholls 2004

Cohort from community not representative of local population

Cohort

Inactive, trivalent

5 to 14 years

ILI

39

91

0

3

Slepushkin 1974

Intraepidemic study of orally administered vaccine as emergency prophylaxis

RCT

Live (oral) H2N2+B

1 to 3 years

Influenza or ARI >= 10 days after vaccination

187

508

271

492

Ritzwoller 2005

Intraepidemic study

Cohort

Inactive, trivalent

6 to 23 months

ILI

65

1129

124

1615

Aksenov 1971

Intraepidemic study

Cohort

Live, H2N2 +B, 3 doses 5 days apart

4 to 7 years

Morbidity due to influenza and ARI

107

760

164

594

Aksenov 1971

Intraepidemic study

Cohort

Live, H2N2 +B, 3 doses 8 to 10 days apart

4 to 7 years

Morbidity due to influenza and ARI

81

728

193

674

Aksenov 1971

Intraepidemic study

Cohort

Live, H2N2 +B, 3 doses 5 days apart

7 to 15 years

Morbidity due to influenza and ARI

143

1358

114

776

ARI: acute respiratory infection
ILI: influenza‐like illness

Figures and Tables -
Table 3. Efficacy and effectiveness data from intraepidemic and non‐typical studies
Comparison 1. Live vaccine versus placebo or no intervention (RCTs by age group)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

6

9175

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.13, 0.32]

1.1 under 2 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 under 6 years

6

9115

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.11, 0.29]

1.3 over 6 years

1

60

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.23, 0.97]

2 Influenza‐like illness Show forest plot

8

188418

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.62, 0.72]

2.1 under 2 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 under 6 years

5

38646

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.57, 0.77]

2.3 over 6 years

8

149772

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.60, 0.74]

Figures and Tables -
Comparison 1. Live vaccine versus placebo or no intervention (RCTs by age group)
Comparison 2. Inactivated vaccine versus placebo or no intervention (RCTs by age group)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

5

1628

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.29, 0.59]

1.1 under 2 years

2

786

Risk Ratio (M‐H, Random, 95% CI)

0.55 [0.18, 1.69]

1.2 under 6 years

2

132

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.34, 1.08]

1.3 over 6 years

3

710

Risk Ratio (M‐H, Random, 95% CI)

0.31 [0.22, 0.45]

2 Influenza‐like illness Show forest plot

5

19388

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.54, 0.76]

2.1 under 2 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 under 6 years

3

476

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.21, 0.69]

2.3 over 6 years

4

18912

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.66, 0.78]

Figures and Tables -
Comparison 2. Inactivated vaccine versus placebo or no intervention (RCTs by age group)
Comparison 3. Live attenuated vaccines (cohort studies by age group)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

1

83

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.35, 0.91]

1.1 under 2 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 under 6 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.3 over 6 years

1

83

Risk Ratio (M‐H, Random, 95% CI)

0.56 [0.35, 0.91]

2 Influenza‐like illness Show forest plot

2

22077

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.57, 0.69]

2.1 under 2 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 under 6 years

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 over 6 years

2

22077

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.57, 0.69]

Figures and Tables -
Comparison 3. Live attenuated vaccines (cohort studies by age group)
Comparison 4. Inactivated vaccines (cohort studies by age group)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

6

1873

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.25, 0.73]

1.1 under 2 years

3

314

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.27, 1.47]

1.2 under 6 years

1

180

Risk Ratio (M‐H, Random, 95% CI)

0.34 [0.13, 0.89]

1.3 over 6 years

2

1379

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.12, 1.11]

2 Influenza‐like illness Show forest plot

11

11935

Risk Ratio (M‐H, Random, 95% CI)

0.53 [0.42, 0.67]

2.1 under 2 years

1

23

Risk Ratio (M‐H, Random, 95% CI)

0.47 [0.23, 0.93]

2.2 under 6 years

5

7046

Risk Ratio (M‐H, Random, 95% CI)

0.74 [0.59, 0.93]

2.3 over 6 years

7

4866

Risk Ratio (M‐H, Random, 95% CI)

0.44 [0.29, 0.68]

3 Otitis media Show forest plot

1

119

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.22, 1.03]

3.1 Children aged 6 months to 5 years

1

119

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.22, 1.03]

Figures and Tables -
Comparison 4. Inactivated vaccines (cohort studies by age group)
Comparison 5. Live vaccine versus placebo (RCTs)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

6

6081

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.11, 0.32]

1.1 Live attenuated vaccines (one‐dose)

5

3038

Risk Ratio (M‐H, Random, 95% CI)

0.23 [0.12, 0.47]

1.2 Live attenuated vaccines (two‐doses)

2

3043

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.04, 0.26]

2 Influenza‐like illness Show forest plot

7

124606

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.60, 0.80]

2.1 Live attenuated vaccines (one‐dose)

2

3306

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.18, 2.22]

2.2 Live attenuated vaccines (two‐doses)

6

121300

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.57, 0.76]

3 Otitis media (all episodes) Show forest plot

2

2873

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.95, 1.01]

4 Working days lost (number of events, parents) Show forest plot

2

2874

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.46, 1.03]

5 Drug prescriptions (number of events) Show forest plot

1

1784

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.87, 1.12]

6 Outpatients attendance for pneumonia and influenza Show forest plot

2

2874

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.59, 0.98]

Figures and Tables -
Comparison 5. Live vaccine versus placebo (RCTs)
Comparison 6. Inactivated vaccine versus placebo (RCTs)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

5

1628

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.28, 0.48]

1.1 Inactivated vaccines (one‐dose)

5

1628

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.28, 0.48]

1.2 Inactivated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Influenza‐like illness Show forest plot

4

19044

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.65, 0.79]

2.1 Inactivated vaccines (one‐dose)

2

267

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.15, 0.81]

2.2 Inactivated vaccines (two‐doses)

2

18777

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.69, 0.76]

Figures and Tables -
Comparison 6. Inactivated vaccine versus placebo (RCTs)
Comparison 7. Case‐control studies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza vs influenza‐like illness (crude data) Show forest plot

9

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Children aged below 6

9

4949

Odds Ratio (M‐H, Random, 95% CI)

0.59 [0.45, 0.77]

1.2 Children aged between 5‐19

1

27

Odds Ratio (M‐H, Random, 95% CI)

0.76 [0.07, 8.66]

2 Influenza vs influenza‐like illness (adj. estimates) Show forest plot

9

Odds Ratio (Random, 95% CI)

Subtotals only

2.1 Children aged below 23 months ‐ fully vaccinated

7

Odds Ratio (Random, 95% CI)

0.60 [0.39, 0.94]

2.2 Children aged between 24‐59 months ‐ fully vaccinated

4

Odds Ratio (Random, 95% CI)

0.40 [0.22, 0.70]

2.3 Children aged between 6 ‐ 59 months ‐ fully vaccinated

5

Odds Ratio (Random, 95% CI)

0.45 [0.32, 0.62]

2.4 Children aged below 14 years old ‐ fully vaccinated

1

Odds Ratio (Random, 95% CI)

0.23 [0.06, 0.84]

3 Influenza‐like illness vs no symptoms Show forest plot

1

488

Odds Ratio (M‐H, Random, 95% CI)

0.49 [0.28, 0.86]

3.1 Inactivated vaccine (one‐dose)

1

244

Odds Ratio (M‐H, Random, 95% CI)

0.53 [0.26, 1.07]

3.2 Inactivated vaccine (two‐doses)

1

244

Odds Ratio (M‐H, Random, 95% CI)

0.44 [0.18, 1.10]

Figures and Tables -
Comparison 7. Case‐control studies
Comparison 8. Vaccine versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Influenza Show forest plot

8

6590

Risk Ratio (M‐H, Random, 95% CI)

0.27 [0.18, 0.42]

1.1 Live attenuated vaccines (one‐dose)

4

1919

Risk Ratio (M‐H, Random, 95% CI)

0.27 [0.12, 0.61]

1.2 Live attenuated vaccines (two‐doses)

2

3043

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.04, 0.26]

1.3 Inactivated vaccines (one‐dose)

5

1628

Risk Ratio (M‐H, Random, 95% CI)

0.36 [0.28, 0.48]

1.4 Inactivated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Influenza‐like illness Show forest plot

8

143650

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.62, 0.77]

2.1 Live attenuated vaccines (one‐dose)

2

3306

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.18, 2.22]

2.2 Live attenuated vaccines (two‐doses)

6

121300

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.57, 0.76]

2.3 Inactivated vaccines (one‐dose)

2

267

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.15, 0.81]

2.4 Inactivated vaccines (two‐doses)

2

18777

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.69, 0.76]

3 Secondary cases Show forest plot

1

123

Risk Ratio (M‐H, Random, 95% CI)

1.68 [0.56, 4.99]

3.1 Live attenuated vaccines (one‐dose)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Live attenuated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Inactivated vaccines (one‐dose)

1

123

Risk Ratio (M‐H, Random, 95% CI)

1.68 [0.56, 4.99]

3.4 Inactivated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 School absenteeism Show forest plot

1

550

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.26, 0.92]

4.1 Live attenuated vaccines (one‐dose)

1

296

Risk Ratio (M‐H, Random, 95% CI)

0.51 [0.22, 1.19]

4.2 Live attenuated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.3 Inactivated vaccines (one‐dose)

1

254

Risk Ratio (M‐H, Random, 95% CI)

0.46 [0.17, 1.22]

4.4 Inactivated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Lower respiratory tract disease Show forest plot

2

1632

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.03, 1.54]

5.1 Live attenuated vaccines (one‐dose)

2

1496

Risk Ratio (M‐H, Random, 95% CI)

0.16 [0.01, 4.45]

5.2 Live attenuated vaccines (two doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.3 Inactivated vaccines (one‐dose)

1

136

Risk Ratio (M‐H, Random, 95% CI)

0.30 [0.01, 6.17]

5.4 Inactivated vaccines (two‐doses)

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Acute otitis media Show forest plot

6

5253

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.79, 1.26]

6.1 Live attenuated vaccines (one‐dose)

3

2585

Risk Ratio (M‐H, Random, 95% CI)

0.42 [0.05, 3.79]

6.2 Live attenuated vaccines (two‐doses)

1

1784

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.95, 1.01]

6.3 Inactivated vaccines (one‐dose)

1

136

Risk Ratio (M‐H, Random, 95% CI)

1.52 [0.10, 23.76]

6.4 Inactivated vaccines (two‐doses)

2

748

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.95, 1.40]

7 Hospitalisation due to acute otitis media Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Inactivated vaccine (two‐doses)

2

765

Risk Ratio (M‐H, Random, 95% CI)

1.41 [0.62, 3.24]

8 Consequences of acute otitis media Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 Inactivated vaccine (two‐doses ‐ visits)

2

765

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.27, 0.23]

8.2 Inactivated vaccine (two‐doses ‐ courses of antibiotics)

2

765

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.36, 0.63]

9 Outpatients attendance for pneumonia and influenza Show forest plot

2

2874

Risk Ratio (M‐H, Random, 95% CI)

0.76 [0.59, 0.98]

9.1 Live attenuated vaccine (one‐dose)

1

1090

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.49, 0.85]

9.2 Live attenuated vaccine (two‐doses)

1

1784

Risk Ratio (M‐H, Random, 95% CI)

0.85 [0.75, 0.96]

10 Working days lost (number of events, parents of children 6‐36 months of age) Show forest plot

2

2874

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.46, 1.03]

10.1 Live attenuated vaccine

2

2874

Risk Ratio (M‐H, Random, 95% CI)

0.69 [0.46, 1.03]

11 Drug prescriptions (number of events, 6‐36 months of age) Show forest plot

1

1784

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.87, 1.12]

11.1 Live attenuated vaccine

1

1784

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.87, 1.12]

Figures and Tables -
Comparison 8. Vaccine versus placebo