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Evaluation of Effectiveness of GSK Biologicals' Pneumococcal Conjugate Vaccine 1024850A Against Invasive Disease (FinIP)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00861380
Recruitment Status : Completed
First Posted : March 13, 2009
Results First Posted : September 25, 2020
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Prevention
Conditions Infections, Streptococcal
Streptococcus Pneumoniae
Interventions Biological: Pneumococcal conjugate vaccine GSK1024850A
Biological: GSK Biologicals' Engerix TM vaccine (Hepatitis B vaccine)
Biological: GSK Biologicals' Havrix TM vaccine (Hepatitis A vaccine)
Enrollment 41188
Recruitment Details This study also served as basis for conducting a long-term evaluation of the impact of vaccination with GSK Biologicals' 10Pn-PD-DiT vaccine. Subjects of the 10PN-PD-DIT-053 (112595) study (NCT00839254-EUDRACT:2008-006551-51) contributed to the objectives of this study.
Pre-assignment Details 41188 subjects were enrolled in the study, 7 subjects didn't receive any vaccination, 41181 subjects started the study. Total population assessed for combined analyses performed on both studies included 45977 subjects, see details in groups description.
Arm/Group Title 10Pn3+1-6W-6M/043 Group 10Pn2+1-6W-6M/043 Group Ctrl-6W-6M/043 Group 10Pn7-11M/043 Group Ctrl7-11M/043 Group 10Pn12-18M/043 Group Ctrl12-18M/043 Group
Hide Arm/Group Description Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Period Title: Overall Study
Started 8427 9112 8872 3689 1812 6249 3020
Completed 0 0 0 0 0 0 0
Not Completed 8427 9112 8872 3689 1812 6249 3020
Reason Not Completed
Withdrawal Information not recorded             8427             9112             8872             3689             1812             6249             3020
Arm/Group Title 10Pn3+1-6W-6M/043 Group 10Pn2+1-6W-6M/043 Group Ctrl-6W-6M/043 Group 10Pn7-11M/043 Group Ctrl7-11M/043 Group 10Pn12-18M/043 Group Ctrl12-18M/043 Group Total
Hide Arm/Group Description Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate. Total of all reporting groups
Overall Number of Baseline Participants 8427 9112 8872 3689 1812 6249 3020 41181
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8427 participants 9112 participants 8872 participants 3689 participants 1812 participants 6249 participants 3020 participants 41181 participants
<=18 years
8427
 100.0%
9112
 100.0%
8872
 100.0%
3689
 100.0%
1812
 100.0%
6249
 100.0%
3020
 100.0%
41181
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 8427 participants 9112 participants 8872 participants 3689 participants 1812 participants 6249 participants 3020 participants 41181 participants
Female
4239
  50.3%
4399
  48.3%
4351
  49.0%
 NA [1]  NA [1]  NA [1]  NA [1]  NA [2] 
Male
4188
  49.7%
4713
  51.7%
4521
  51.0%
 NA [1]  NA [1]  NA [1]  NA [1]  NA [2] 
[1]
Gender characteristics were not recorded for this group
[2]
Total not calculated because data are not available (NA) in one or more arms.
1.Primary Outcome
Title Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
0.000
(0.000 to 0.172)
0.564
(0.291 to 0.984)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn3+1-6W-6M/043+053 Group, Ctrl-6W-6M/043+053 Group
Comments Analysis aimed at providing an estimate of vaccine effectiveness (VE) at preventing culture-confirmed IPD by comparing PYARs between groups taking into account the following parameters: T, n, n+ (number of clusters with at least one event culture-confirmed ID), and n/T. VE of the 10Pn vaccine in preventing culture-confirmed IPD due to the 10 vaccine serotypes was demonstrated if the 2-sided p-value calculated for the null hypothesis H0 =(vaccine-type [VT] IPD VE = 0%) was lower than (<) 5%.
Type of Statistical Test Superiority
Comments VE (defined as 1 minus Relative Risk (RR)) was calculated by comparing numbers of culture-confirmed IPD. The number of subjects with IPD in each cluster was compared between groups (10PN3+1 vs Control). This comparison was done using a negative binomial log-linear model with correction for dispersion group- and cluster- related effect.
Statistical Test of Hypothesis P-Value <0.0001
Comments P-value was calculated using a classical log linear Poisson regression with strata, without taking into account the multiplicity of the endpoints.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter VE (1-RR)
Estimated Value 100
Confidence Interval (2-Sided) 95%
82.8 to 100
Estimation Comments [Not Specified]
2.Primary Outcome
Title Person Year Rate as Regards Subjects With Culture-confirmed IPD Due to Any of the 10 Pneumococcal Vaccine Serotypes. In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description The PYAR (Person-Year Rate) as regards subjects with culture-confirmed invasive pneumococcal disease (IPD) due to any of the pneumococcal vaccine serotypes was tabulated (vaccine pneumococcal serotypes = serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F). PYAR was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
0.048
(0.001 to 0.270)
0.564
(0.291 to 0.984)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn2+1-6W-6M/043+053 Group, Ctrl-6W-6M/043+053 Group
Comments Analysis aimed at providing an estimate of vaccine effectiveness (VE) at preventing culture-confirmed IPD by comparing PYARs between groups taking into account the following parameters: T, n, n+ (number of clusters with at least one event culture-confirmed ID), and n/T. VE of the 10Pn vaccine in preventing culture-confirmed IPD due to the 10 vaccine serotypes was demonstrated if the 2-sided p-value calculated for the null hypothesis H0 = (vaccine-type [VT] IPD VE = 0%) was lower than (<) 5%.
Type of Statistical Test Superiority
Comments VE (defined as 1 minus Relative Risk (RR)) was calculated by comparing numbers of culture-confirmed IPD. The number of subjects with IPD in each cluster was compared between groups (10PN2+1vsControl). This comparison was done using a negative binomial log-linear model with correction for dispersion group- and cluster- related effect.
Statistical Test of Hypothesis P-Value = 0.0009
Comments p-value was calculated using a classical log linear Poisson regression with strata, without taking into account the multiplicity of the endpoints.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter VE (1-RR)
Estimated Value 91.8
Confidence Interval (2-Sided) 95%
58.3 to 99.6
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course (Till End of Blinded ID FU Period)
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Culture confirmed ID
0.093
(0.011 to 0.336)
0.845
(0.501 to 1.336)
Pneumococcal invasive disease (IPD)
0.000
(0.000 to 0.172)
0.657
(0.359 to 1.103)
Serotype 4
0.000
(0.000 to 0.172)
0.000
(0.000 to 0.173)
Serotype 6B
0.000
(0.000 to 0.172)
0.235
(0.076 to 0.548)
Serotype 7F
0.000
(0.000 to 0.172)
0.000
(0.000 to 0.173)
Serotype 14
0.000
(0.000 to 0.172)
0.188
(0.051 to 0.481)
Serotype 18C
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Serotype 19F
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Serotype 23F
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Cross-reactive serotypes
0.000
(0.000 to 0.172)
0.094
(0.011 to 0.339)
Serotype 6A
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Serotype 19A
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Other pneumococcal serotypes
0.000
(0.000 to 0.172)
0.000
(0.000 to 0.173)
Serotype 3
0.000
(0.000 to 0.172)
0.000
(0.000 to 0.173)
Serotype 15C
0.000
(0.000 to 0.172)
0.000
(0.000 to 0.173)
H. influenzae ID
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Non-typeable (NTHI)
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
Other bacteria
0.093
(0.011 to 0.336)
0.188
(0.051 to 0.481)
Neisseria meningitidis
0.093
(0.011 to 0.336)
0.047
(0.001 to 0.262)
Streptococcus pyogenes
0.000
(0.000 to 0.172)
0.094
(0.011 to 0.339)
Moraxella catarrhalis
0.000
(0.000 to 0.172)
0.047
(0.001 to 0.262)
4.Secondary Outcome
Title Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course (Till End of Blinded ID FU Period)
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Culture confirmed ID
0.194
(0.053 to 0.496)
0.845
(0.501 to 1.336)
Pneumococcal invasive disease (IPD)
0.097
(0.012 to 0.350)
0.657
(0.359 to 1.103)
Vaccine serotypes (vaccine type-IPD)
0.048
(0.001 to 0.270)
0.564
(0.291 to 0.984)
Serotype 4
0.000
(0.000 to 0.179)
0.000
(0.000 to 0.173)
Serotype 6B
0.000
(0.000 to 0.179)
0.235
(0.076 to 0.548)
Serotype 7F
0.048
(0.001 to 0.270)
0.000
(0.000 to 0.173)
Serotype 14
0.000
(0.000 to 0.179)
0.188
(0.051 to 0.481)
Serotype 18C
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
Serotype 19F
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
Serotype 23F
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
Cross-reactive serotypes
0.000
(0.000 to 0.179)
0.094
(0.011 to 0.339)
Serotype 6A
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
Serotype 19A
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
Other pneumococcal serotypes
0.048
(0.001 to 0.270)
0.000
(0.000 to 0.173)
Serotype 3
0.048
(0.001 to 0.270)
0.000
(0.000 to 0.173)
Serotype 15C
0.000
(0.000 to 0.179)
0.000
(0.000 to 0.173)
H. influenzae ID
0.048
(0.001 to 0.270)
0.047
(0.001 to 0.262)
Non-typeable (NTHI)
0.048
(0.001 to 0.270)
0.047
(0.001 to 0.262)
Other bacteria
0.048
(0.001 to 0.270)
0.188
(0.051 to 0.481)
Neisseria meningitidis
0.048
(0.001 to 0.270)
0.047
(0.001 to 0.262)
Streptococcus pyogenes
0.000
(0.000 to 0.179)
0.094
(0.001 to 0.339)
Moraxella catarrhalis
0.000
(0.000 to 0.179)
0.047
(0.001 to 0.262)
5.Secondary Outcome
Title Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1908
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Culture confirmed ID
0.000
(0.000 to 0.410)
0.446
(0.054 to 1.612)
Pneumococcal invasive disease (IPD)
0.000
(0.000 to 0.410)
0.446
(0.054 to 1.612)
Vaccine serotypes (vaccine type-IPD)
0.000
(0.000 to 0.410)
0.446
(0.054 to 1.612)
Serotype 4
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 6B
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 7F
0.000
(0.000 to 0.410)
0.223
(0.006 to 1.243)
Serotype 14
0.000
(0.000 to 0.410)
0.223
(0.006 to 1.243)
Serotype 18C
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 19F
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 23F
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Cross-reactive serotypes
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 6A
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 19A
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Other pneumococcal serotypes
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 3
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Serotype 15C
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
H. influenzae ID
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Non-typeable (NTHI)
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Other bacteria
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
6.Secondary Outcome
Title Person Year Rate in the Prevention of Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population)
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log- likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6535 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Culture confirmed ID
0.000
(0.000 to 0.240)
0.674
(0.219 to 1.572)
Pneumococcal invasive disease (IPD)
0.000
(0.000 to 0.240)
0.674
(0.219 to 1.572)
Vaccine serotypes (vaccine type-IPD)
0.000
(0.000 to 0.240)
0.404
(0.083 to 1.181)
Serotype 4
0.000
(0.000 to 0.240)
0.135
(0.003 to 0.751)
Serotype 6B
0.000
(0.000 to 0.240)
0.135
(0.003 to 0.751)
Serotype 7F
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Serotype 14
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Serotype 18C
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Serotype 19F
0.000
(0.000 to 0.240)
0.135
(0.0003 to 0.751)
Serotype 23F
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Cross-reactive serotypes
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Serotype 6A
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Serotype 19A
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Other pneumococcal serotypes
0.000
(0.000 to 0.240)
0.269
(0.033 to 0.974)
Serotype 3
0.000
(0.000 to 0.240)
0.135
(0.003 to 0.751)
Serotype 15C
0.000
(0.000 to 0.240)
0.135
(0.003 to 0.751)
H. influenzae ID
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Non-typeable (NTHI)
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Other bacteria
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 2626735.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 14.657
Confidence Interval (2-Sided) 95%
13.229 to 16.197
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 1354702.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 13.582
Confidence Interval (2-Sided) 95%
11.691 to 15.693
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 2626735.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 8.452
Confidence Interval (2-Sided) 95%
7.376 to 9.639
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 1354702.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 7.603
Confidence Interval (2-Sided) 95%
6.206 to 9.221
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 2626735.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 1.637
Confidence Interval (2-Sided) 95%
1.185 to 2.205
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons = 1354702.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 1.845
Confidence Interval (2-Sided) 95%
1.194 to 2.724
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as . 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons = 2626735.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 3.997
Confidence Interval (2-Sided) 95%
3.269 to 4.839
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons = 1354702.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 3.322
Confidence Interval (2-Sided) 95%
2.423 to 4.445
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2636783.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 14.487
Confidence Interval (2-Sided) 95%
13.071 to 16.015
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1360966.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 13.740
Confidence Interval (2-Sided) 95%
11.841 to 15.857
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2636783.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 7.813
Confidence Interval (2-Sided) 95%
6.782 to 8.955
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1360966.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 7.789
Confidence Interval (2-Sided) 95%
6.377 to 9.420
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2636783.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 2.313
Confidence Interval (2-Sided) 95%
1.770 to 2.972
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1360966.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 1.984
Confidence Interval (2-Sided) 95%
1.307 to 2.886
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model without strata). Total number of non-vaccinated persons =2636783.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model without strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 4.172
Confidence Interval (2-Sided) 95%
3.429 to 5.028
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model without strata). Total number of non-vaccinated persons =1360966.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model without strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 3.968
Confidence Interval (2-Sided) 95%
2.981 to 5.177
Estimation Comments [Not Specified]
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2654010.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 14.017
Confidence Interval (2-Sided) 95%
12.628 to 15.516
Estimation Comments [Not Specified]
Hide Statistical Analysis 18
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (any serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1367343.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 15.066
Confidence Interval (2-Sided) 95%
13.079 to 17.269
Estimation Comments [Not Specified]
Hide Statistical Analysis 19
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2654010.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 5.916
Confidence Interval (2-Sided) 95%
5.026 to 6.917
Estimation Comments [Not Specified]
Hide Statistical Analysis 20
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine serotype), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1367343.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 8.557
Confidence Interval (2-Sided) 95%
7.077 to 10.255
Estimation Comments [Not Specified]
Hide Statistical Analysis 21
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons =2654010.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 2.977
Confidence Interval (2-Sided) 95%
2.357 to 3.710
Estimation Comments [Not Specified]
Hide Statistical Analysis 22
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata). Total number of non-vaccinated persons =1367343.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Regression, Linear
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 2.048
Confidence Interval (2-Sided) 95%
1.361 to 2.960
Estimation Comments [Not Specified]
Hide Statistical Analysis 23
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2654010.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 5.011
Confidence Interval (2-Sided) 95%
4.196 to 5.939
Estimation Comments [Not Specified]
Hide Statistical Analysis 24
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Culture-confirmed IPD (non-vaccine & non-vaccine related), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a culture confirmed IPD divided by sum of follow-up period expressed in years (per 100000), as well as the 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1367343.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 4.315
Confidence Interval (2-Sided) 95%
3.285 to 5.566
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Person Year Rate in the Prevention of Probable Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Probable cases of IPD
0.000
(0.000 to 0.172)
0.141
(0.029 to 0.412)
Confirmed or probable cases of IPD
0.000
(0.000 to 0.172)
0.798
(0.465 to 1.278)
8.Secondary Outcome
Title Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Probable cases of IPD
0.000
(0.000 to 0.179)
0.141
(0.029 to 0.412)
Confirmed or probable cases of IPD
0.097
(0.012 to 0.350)
0.798
(0.465 to 1.278)
9.Secondary Outcome
Title Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1908
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Probable cases of IPD
0.000
(0.000 to 0.410)
0.000
(0.000 to 0.823)
Confirmed or probable cases of IPD
0.000
(0.000 to 0.410)
0.446
(0.054 to 1.612)
10.Secondary Outcome
Title Person Year Rate in the Prevention of Probable or Culture-confirmed Invasive Disease (ID)- In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population)
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a probable or culture confirmed ID) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata. Data were not collected regarding indirect effects.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (The blinded ID Follow-up period lasted at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6535 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Probable cases of IPD
0.000
(0.000 to 0.240)
0.000
(0.000 to 0.497)
Confirmed or probable cases of IPD
0.000
(0.000 to 0.240)
0.674
(0.219 to 1.572)
11.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (=number of subjects with hospital-diagnosed pneumonia) divided by T (=sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
10.131
(8.804 to 11.601)
13.854
(12.287 to 15.566)
12.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
10.155
(8.800 to 11.660)
13.854
(12.287 to 15.566)
13.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia- In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1907
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
10.263
(8.242 to 12.630)
15.752
(12.232 to 19.970)
14.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population)
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. Hospital-diagnosed pneumonia (HDP) cases identified based on hospital discharge diagnosis using international Classification of Disease (ICD)-10 diagnosis codes: J10.0 (Influenza with HDP, other influenza virus identified), J11.0 (Influenza with HDP, virus not identified), J12 (Viral HDP, not elsewhere classified), J13 (HDP due to Sp.), J14 (for HDP due to Hi.), J15 (all HDP, not elsewhere classified), J16 (HDP due to other infectious organisms, not elsewhere classified), J17 (HDP in diseases classified elsewhere), J18 (HDP organism unspecified), J85.1 (Abscess of lung with HDP), and J86 (Pyothorax including empyema).
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6534 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
9.322
(7.832 to 11.013)
11.739
(9.363 to 14.533)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2626735.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 9.218
Confidence Interval (2-Sided) 95%
9.103 to 9.335
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1354702.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 9.212
Confidence Interval (2-Sided) 95%
9.052 to 9.375
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2636783.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 10.500
Confidence Interval (2-Sided) 95%
10.378 to 10.624
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1360966.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 10.429
Confidence Interval (2-Sided) 95%
10.259 to 10.601
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =2654010.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 10.118
Confidence Interval (2-Sided) 95%
9.997 to 10.239
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Hospital-diagnosed Pneumonia, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 5 to 99+ Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with a Hospital-diagnosed Pneumonia divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =1367343.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 9.921
Confidence Interval (2-Sided) 95%
9.755 to 10.088
Estimation Comments [Not Specified]
15.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia With Chest X-ray (CXR) Reading According to WHO Criteria- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Consolidated pneumonia
2.181
(1.591 to 2.919)
3.965
(3.149 to 4.929)
Non-consolidated pneumonia
2.908
(2.219 to 3.744)
2.937
(2.241 to 3.781)
Consolidated or non- consolidated pneumonia
5.090
(4.163 to 6.161)
6.903
(5.810 to 8.141)
16.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Consolidated pneumonia
2.273
(1.658 to 3.042)
3.965
(3.149 to 4.929)
Non-consolidated pneumonia
2.627
(1.962 to 3.445)
2.937
(2.241 to 3.781)
Consolidated or non- consolidated pneumonia
4.901
(3.974 to 5.978)
6.903
(5.810 to 8.141)
17.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1907
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Consolidated pneumonia
1.960
(1.142 to 3.139)
4.401
(2.650 to 6.873)
Non-consolidated pneumonia
3.344
(2.240 to 4.803)
4.865
(3.011 to 7.436)
Consolidated or non- consolidated pneumonia
5.305
(3.884 to 7.076)
9.266
(6.620 to 12.618)
18.Secondary Outcome
Title Person Year Rate in Reducing Hospital-diagnosed Pneumonia With CXR Reading According to WHO Criteria - In Children Starting Vaccination in the 12-18 Months Schedule
Hide Description PYAR was calculated: n (= number of subjects with hospital-diagnosed pneumonia [HDP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata for non-consolidated HDP and without strata for consolidated HDP). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. CXR HDP was defined as a HDP case with the presence of abnormal pulmonary infiltrates on the CXR as per independent review panel judgement using WHO methodology. Abnormal pulmonary infiltrates could be either with (Consolidated HDP) or without (Non-consolidated HDP) alveolar consolidation/pleural effusion. New cases of HDP and CXR HDP were based on a 30-day rule, i.e. a new episode was considered if at least a 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6534 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Consolidated pneumonia
1.824
(1.202 to 2.654)
3.494
(2.261 to 5.157)
Non-consolidated pneumonia
2.837
(2.045 to 3.835)
2.935
(1.817 to 4.486)
Consolidated or non- consolidated pneumonia
4.661
(3.626 to 5.899)
6.428
(4.706 to 8.574)
19.Secondary Outcome
Title Person Year Rate in Prevention of All Tympanostomy Tube Placements- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
68.735
(65.203 to 72.408)
79.504
(75.683 to 83.467)
20.Secondary Outcome
Title Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
66.083
(62.550 to 69.764)
79.504
(75.683 to 83.467)
21.Secondary Outcome
Title Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1907
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
68.153
(62.769 to 73.876)
79.920
(71.708 to 88.814)
22.Secondary Outcome
Title Person Year Rate in Prevention of All Tympanostomy Tube Placements - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population)
Hide Description PYAR was calculated: n (= number of subjects with tympanostomy tube placement[TTP]) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. A TTP episode was defined as a TTP episode classified under the DCA 20 code in the Finnish National Institute of Health and Welfare (THL) and Social Insurance Institution of Finland (KELA) registers, using the Nordic Centre for Classifications in Health Care (NOMESCO) Classification of Surgical Procedures (NCSP), version 1.12 from January 2008, and could refer to either an unilateral or a bilateral TTP procedure. New episodes of TTP defined according to a 30-day rule meaning that a new episode was considered if at least 30-day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6534 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
56.809
(53.034 to 60.782)
58.973
(53.480 to 64.877)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =229978.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 22.624
Confidence Interval (2-Sided) 95%
22.020 to 23.240
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =120190.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 22.747
Confidence Interval (2-Sided) 95%
21.912 to 23.606
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =214181.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 24.503
Confidence Interval (2-Sided) 95%
23.852 to 25.166
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =112060.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 26.236
Confidence Interval (2-Sided) 95%
25.308 to 27.189
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =211914.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 27.502
Confidence Interval (2-Sided) 95%
26.810 to 28.207
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111071.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 26.100
Confidence Interval 95%
25.171 to 27.055
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =213913.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 28.661
Confidence Interval (2-Sided) 95%
27.958 to 29.377
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Tympanostomy Tube Placements, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Tympanostomy Tube Placement divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111414.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 29.835
Confidence Interval (2-Sided) 95%
28.843 to 30.850
Estimation Comments [Not Specified]
23.Secondary Outcome
Title Person Year Rate in Prevention of All Antimicrobial Prescriptions- In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Antimicrobial prescriptions (ATC code J01)
1592.585
(1575.411 to 1609.901)
1706.194
(1688.328 to 1724.202)
For otitis media and respiratory infections
1451.141
(1434.749 to 1467.674)
1565.692
(1548.579 to 1582.947)
24.Secondary Outcome
Title Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 2-dose Primary Vaccination Course
Hide Description PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 2-dose primary vaccination course.
Arm/Group Title 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10054 10200
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Antimicrobial prescriptions (ATC code J01)
1552.493
(1535.183 to 1569.950)
1706.194
(1688.328 to 1724.202)
For otitis media and respiratory infections
1415.983
(1399.453 to 1432.659)
1565.692
(1548.579 to 1582.947)
25.Secondary Outcome
Title Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 7-11 Months Schedule
Hide Description PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 7 and 11 months of age.
Arm/Group Title 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 3880 1907
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Antimicrobial prescriptions (ATC code J01)
1536.618
(1510.637 to 1562.934)
1649.360
(1611.269 to 1688.124)
For otitis media and respiratory infections
1390.856
(1366.143 to 1415.903)
1499.713
(1463.401 to 1536.698)
26.Secondary Outcome
Title Person Year Rate in Prevention of All Antimicrobial Prescriptions - In Children Starting Vaccination in the 12-18 Months Schedule (+ Indirect Effects on the Unvaccinated Population)
Hide Description PYAR was calculated: n (= number of subjects with antimicrobial prescriptions (APs)) divided by T (= sum of follow-up (FU) period expressed in years) (per 1000) with 95% CI (2-sided profile log-likelihood ratio 95% CI-classical log linear Poisson regression with strata). FU period considered as period between Dose 1 administration and cut-off date of 31 December 2011. An APs episode was an episode of APs to an infant/child falling under following Anatomic Therapeutic Chemical [ATC] codes: J01 (APs) and following codes for AP usually recommended for otitis media (OM) and respiratory tract infections (RTI). "For OM and RTI" category corresponds to following definition: APs for antibacterial usually recommended for OM and RTI (ATC codes: J01CA04, J01CR02, J01CE02, J01DC02, J01DC04, J01EE02, J01FA09 and J01FA10). New episodes of APs were analyzed according to a 2-day rule meaning new episode considered if at least 2 day interval elapsed from the onset of the previous episode.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - FU mean time=27 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Catch-up Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with a 2-dose primary vaccination between 12 and 18 months of age.
Arm/Group Title 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 6534 3126
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Antimicrobial prescriptions (ATC code J01)
1315.936
(1297.521 to 1334.547)
1421.774
(1394.280 to 1449.675)
For otitis media and respiratory infections
1177.729
(1160.312 to 1195.343)
1271.268
(1245.277 to 1297.665)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =229978.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 816.813
Confidence Interval (2-Sided) 95%
815.226 to 818.392
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =120190.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 841.176
Confidence Interval (2-Sided) 95%
839.098 to 843.239
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for Acute Otitis Media (AOM)/Respiratory Tract Infections (RTI), number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =229978.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 702.245
Confidence Interval (2-Sided) 95%
700.372 to 704.114
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2009, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =120190.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 720.900
Confidence Interval (2-Sided) 95%
718.355 to 723.435
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =214181.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 929.844
Confidence Interval (2-Sided) 95%
928.755 to 930.923
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =112060.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 953.025
Confidence Interval (2-Sided) 95%
951.770 to 954.257
Estimation Comments [Not Specified]
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =214181.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 804.703
Confidence Interval (2-Sided) 95%
803.017 to 806.380
Estimation Comments [Not Specified]
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2010, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =112060.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 818.660
Confidence Interval (2-Sided) 95%
816.391 to 820.912
Estimation Comments [Not Specified]
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =211914.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 916.079
Confidence Interval (2-Sided) 95%
914.891 to 917.256
Estimation Comments [Not Specified]
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111071.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 928.568
Confidence Interval (2-Sided) 95%
927.038 to 930.076
Estimation Comments [Not Specified]
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =211914.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 796.894
Confidence Interval 95%
795.175 to 798.605
Estimation Comments [Not Specified]
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2011, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111071.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 803.918
Confidence Interval (2-Sided) 95%
801.571 to 806.250
Estimation Comments [Not Specified]
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =213913.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 865.679
Confidence Interval (2-Sided) 95%
864.227 to 867.121
Estimation Comments [Not Specified]
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111414.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 871.749
Confidence Interval (2-Sided) 95%
869.771 to 873.707
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection 10Pn12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any 10PN-PD-DIT vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received 10Pn-PD-DiT vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =213913.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 753.423
Confidence Interval (2-Sided) 95%
751.591 to 755.249
Estimation Comments [Not Specified]
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Ctrl12-18M/043+053 Group
Comments For indirect effectiveness analysis at preventing Antimicrobial Prescriptions recommended for AOM/RTI, number of events in the unvaccinated cohort, which occurred around 6 months or more after study start was compared with treated group numbers (applicable to any control (HAV or HBV) vaccine - age stratum schedules).
Type of Statistical Test Other
Comments In 0 to 7 Years Old Population, in Year 2012, for Non-vaccinated persons living in study cluster areas, in which study participants received control vaccine, PYAR was calculated (= number of subjects reported with recommended Antimicrobial Prescriptions divided by sum of follow-up period expressed in years (per 1000), as well as 95% CI (2-sided profile log-likelihood ratio 95% CI using a Negative Binomial regression model with strata). Total number of non-vaccinated persons =111414.
Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Negative Binomial model with strata
Comments Analysis performed on non-vaccinated persons, not enrolled in the study, but living in cluster areas in which study participants received vaccine.
Method of Estimation Estimation Parameter PYAR
Estimated Value 755.542
Confidence Interval (2-Sided) 95%
753.008 to 758.064
Estimation Comments [Not Specified]
27.Secondary Outcome
Title Number of Subjects Classified by Antimicrobial Susceptiblity of IPD Isolates in Children Starting Vaccination Within 7 Months of Life and Assigned to a 2 or 3-dose Primary Vaccination Course
Hide Description Antimicrobial susceptibility classification of IPD isolates reported during IPD follow-up with percentages for each serotype for the following categories: S= susceptible; I = intermediate ; R = resistant; N = not available.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end date of the follow-up (31 December 2011) - mean FU time=24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 0 2 24
Measure Type: Count of Participants
Unit of Measure: Participants
Serotype-4 -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-6A -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-6B -Pencillin-I
0
   0.0%
3
  12.5%
Serotype-6B -Pencillin-R
0
   0.0%
1
   4.2%
Serotype-6B -Pencillin-S
0
   0.0%
2
   8.3%
Serotype-7F -Pencillin-S
1
  50.0%
1
   4.2%
Serotype-14 -Pencillin-I
0
   0.0%
2
   8.3%
Serotype-14 -Pencillin-R
0
   0.0%
1
   4.2%
Serotype-14 -Pencillin-S
0
   0.0%
2
   8.3%
Serotype-15C -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-18C -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-19A -Pencillin-I
0
   0.0%
1
   4.2%
Serotype-19F -Pencillin-I
0
   0.0%
1
   4.2%
Serotype-19F -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-23F -Pencillin-S
0
   0.0%
1
   4.2%
Serotype-N -Pencillin-N
1
  50.0%
4
  16.7%
Serotype-4 -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-6A -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-6B -Erythromycin-R
0
   0.0%
5
  20.8%
Serotype-6B -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-7F -Erythromycin-S
1
  50.0%
1
   4.2%
Serotype-14 -Erythromycin-R
0
   0.0%
4
  16.7%
Serotype-14 -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-15C -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-18C -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-19A -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-19F -Erythromycin-R
0
   0.0%
1
   4.2%
Serotype-19F -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-23F -Erythromycin-S
0
   0.0%
1
   4.2%
Serotype-N -Erythromycin-N
1
  50.0%
4
  16.7%
Serotype-4 -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-6A -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-6B -Tetracyclin-R
0
   0.0%
4
  16.7%
Serotype-6B -Tetracyclin-S
0
   0.0%
2
   8.3%
Serotype-7F -Tetracyclin-S
1
  50.0%
1
   4.2%
Serotype-14 -Tetracyclin-S
0
   0.0%
5
  20.8%
Serotype-15C -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-18C -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-19A -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-19F -Tetracyclin-R
0
   0.0%
1
   4.2%
Serotype-19F -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-23F -Tetracyclin-S
0
   0.0%
1
   4.2%
Serotype-N -Tetracyclin-N
1
  50.0%
4
  16.7%
Serotype-4 -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-6A -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-6B -Levoffloxacin-S
0
   0.0%
6
  25.0%
Serotype-7F -Levoffloxacin-S
1
  50.0%
1
   4.2%
Serotype-14 -Levoffloxacin-S
0
   0.0%
5
  20.8%
Serotype-15C -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-18C -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-19A -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-19F -Levoffloxacin-S
0
   0.0%
2
   8.3%
Serotype-23F -Levoffloxacin-S
0
   0.0%
1
   4.2%
Serotype-N -Levoffloxacin-N
1
  50.0%
4
  16.7%
Serotype-4 -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-6A -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-6B -Ceftriaxone-S
0
   0.0%
6
  25.0%
Serotype-7F -Ceftriaxone-S
1
  50.0%
1
   4.2%
Serotype-14 -Ceftriaxone-I
0
   0.0%
1
   4.2%
Serotype-14 -Ceftriaxone-S
0
   0.0%
4
  16.7%
Serotype-15C -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-18C -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-19A -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-19F -Ceftriaxone-S
0
   0.0%
2
   8.3%
Serotype-23F -Ceftriaxone-S
0
   0.0%
1
   4.2%
Serotype-N -Ceftriaxone-N
1
  50.0%
4
  16.7%
Serotype-4 -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-6A -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-6B -Clindamycin-R
0
   0.0%
4
  16.7%
Serotype-6B -Clindamycin-S
0
   0.0%
2
   8.3%
Serotype-7F -Clindamycin-S
1
  50.0%
1
   4.2%
Serotype-14 -Clindamycin-N
0
   0.0%
1
   4.2%
Serotype-14 -Clindamycin-S
0
   0.0%
4
  16.7%
Serotype-15C -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-18C -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-19A -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-19F -Clindamycin-R
0
   0.0%
1
   4.2%
Serotype-19F -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-23F -Clindamycin-S
0
   0.0%
1
   4.2%
Serotype-N -Clindamycin-N
1
  50.0%
4
  16.7%
28.Secondary Outcome
Title Number of Subjects With Lower Respiratory Tract Infections (LRTIs) (in a Subset of Subjects in Turku Area)
Hide Description Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one LRTI any time after the administration of the first vaccine dose was tabulated.
Time Frame From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in a subset of vaccinated subjects including all vaccinated subjects enrolled in the 10PN-PD-DIT-053 study in the Turku area and those vaccinated subjects enrolled in the 10PN-PD-DIT-043 study in the Turku area who agreed to take part in this assessment.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PDDiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 243 190 171 31 22 62 48
Measure Type: Count of Participants
Unit of Measure: Participants
19
   7.8%
19
  10.0%
19
  11.1%
3
   9.7%
1
   4.5%
5
   8.1%
2
   4.2%
29.Secondary Outcome
Title Number of Subjects With Upper Respiratory Tract Infections (URTIs) (in a Subset of Subjects in Turku Area)
Hide Description Analysis of this outcome was performed in the Turku area. The number of subjects reporting at least one URTI any time after the administration of the first vaccine dose was tabulated.
Time Frame From the administration of the first vaccine dose till the end of the blinded invasive disease (ID) Follow-up period (at least 30 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed in a subset of vaccinated subjects including all vaccinated subjects enrolled in the 10PN-PD-DIT-053 study in the Turku area and those vaccinated subjects enrolled in the 10PN-PD-DIT-043 study in the Turku area who agreed to take part in this assessment.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PDDiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 243 190 171 31 22 62 48
Measure Type: Count of Participants
Unit of Measure: Participants
158
  65.0%
124
  65.3%
94
  55.0%
14
  45.2%
15
  68.2%
27
  43.5%
19
  39.6%
30.Secondary Outcome
Title Number of Subjects With SAEs Reported During the Blinded Invasive Disease Phase, of the Study
Hide Description

An event is defined as 'serious' when it meets one of the pre-defined outcomes described below: results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation; results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject.

Medical or scientific judgement should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also be considered serious.
Time Frame For Month 0 till the end of the blinded ID Follow-Up, (at least 30 months from study start)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10Pn3+1-6W-6M/043 Group 10Pn2+1-6W-6M/043 Group Ctrl-6W-6M/043 Group 10Pn7-11M/043 Group Ctrl7-11M/043 Group 10Pn12-18M/043 Group Ctrl12-18M/043 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). The vaccine was administered intramuscularly in the thigh.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) study, aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). The vaccine was administered intramuscularly in the thigh or in the deltoid region of upper arm, provided the muscle size was adequate.
Overall Number of Participants Analyzed 8427 9112 8872 3689 1812 6249 3020
Measure Type: Count of Participants
Unit of Measure: Participants
6
   0.1%
7
   0.1%
8
   0.1%
3
   0.1%
2
   0.1%
2
   0.0%
2
   0.1%
31.Secondary Outcome
Title Number of Subjects Enrolled and Vaccinated in the 10PN-PD-DIT-043 and 10PN-PD-DIT-053 Study With Post-study SAEs Reported Via Passive Surveillance- Subjects Enrolled Aged 6 Weeks to 6 Months and 7 to 18 Months
Hide Description

An event is defined as 'serious' when it meets one of the pre-defined outcomes described below: results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation; results in disability/incapacity, or is a congenital anomaly/birth defect in the offspring of a study subject.

Medical or scientific judgement should be exercised in deciding whether reporting is appropriate in other situations, such as important medical events that may not be immediately life-threatening or result in death or hospitalisation but may jeopardize the subject or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. These should also be considered serious.
Time Frame From the end of the blinded ID Follow-Up period(at least 30 months from study start) up to the end of 18-month period after study unblinding
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group 10Pn2+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group 10Pn7-11M/043+053 Group Ctrl7-11M/043+053 Group 10Pn12-18M/043+053 Group Ctrl12-18M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 942 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for 10Pn2+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 191 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for 10Pn7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 96 subjects) studies, pooled, and aged 7 to 11 months at enrolment. Subjects received the Engerix B (called also HBV) vaccine according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (11-17M Schedule). Refer to group description for Ctrl7-11M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 286 subjects) studies, pooled, aged 12 to 18 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for 10Pn12-18M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 106 subjects) studies, pooled, and aged 12 to 18 months at enrolment. Subjects received the Havrix (called also HAV) vaccine according to a 2-dose vaccination with an interval of at least and preferably 6 months between doses (12-18M Schedule). Refer to group description for Ctrl12-18M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10273 10054 10201 3880 1908 6535 3126
Measure Type: Count of Participants
Unit of Measure: Participants
1
   0.0%
2
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
32.Secondary Outcome
Title Culture-confirmed Invasive Disease (ID) Person Year Rate - In Children Starting Vaccination Within 7 Months of Life and Assigned to a 3-dose Primary Vaccination Course Till End of LT FU Period
Hide Description The PYAR (Person-Year Rate) was calculated as follows n (= number of subjects reported with a culture confirmed IPD) divided by T (= sum of follow-up period expressed in years) (per 1000) as well as the corresponding 95% confidence interval (CI), calculated as a 2-sided profile log-likelihood ratio 95% CI using a classical log linear Poisson regression with strata.
Time Frame Period of follow-up was any time after the administration of first vaccine dose till the end of the long-term Follow-up period (The Follow-up period lasted at least 77 months)
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis was performed on the Infant Vaccinated cohort, which included all vaccinated,subjects in the 10PN-PD-DIT-043 study and vaccinated subjects of 10PN-PD-DIT-053 study who contributed to the effectiveness analysis, with first dose of study vaccine below 7 months of age and assigned to a 3-dose primary vaccination course.
Arm/Group Title 10Pn3+1-6W-6M/043+053 Group Ctrl-6W-6M/043+053 Group
Hide Arm/Group Description:
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PDDIT-053 (NCT00839254 - EUDRACT 2008- 006551-51) (i.e. 1846 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Synflorix (called also 10Pn-PD-DiT, 10Pn or GSK1024850A) vaccine according to a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses, followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule). Refer to group description for 10Pn3+1-6W-6M/043 Group for vaccine specifics and administration route in this group.
Subjects in this group were subjects enrolled in the 10PN-PD-DIT-043 (NCT00861380 - EUDRACT 2008-005149-48) and 10PN-PD-DIT-053 (NCT00839254 - EUDRACT 2008-006551-51) (i.e. 1329 subjects) studies, pooled, and aged 6 weeks to 6 months at enrolment. Subjects received the Engerix B vaccine (called also HBV vaccine) according to either a 3-dose primary vaccination schedule with an interval of at least 4 weeks between doses followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (3+1 Infant Schedule), or according to a 2-dose primary vaccination with an interval of at least 8 weeks followed by a booster dose of the same vaccine with an interval of preferably 6 months since the previous vaccine dose (minimum 4 months) (2+1 Infant Schedule). Refer to group description for Ctrl6W-6M/043 Group for vaccine specifics and administration route in this group.
Overall Number of Participants Analyzed 10272 10201
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Participants per 1000 person-years
Culture confirmed ID
0.046
(0.013 to 0.118)
0.268
(0.170 to 0.402)
Pneumococcal invasive disease (IPD)
0.023
(0.003 to 0.084)
0.210
(0.124 to 0.331)
Vaccine serotypes (vaccine type-IPD)
0.0
(0.0 to 0.043)
0.140
(0.072 to 0.244)
Serotype 4
0.0
(0.0 to 0.043)
0.0
(0.0 to 0.043)
Serotype 6B
0.0
(0.0 to 0.043)
0.058
(0.019 to 0.136)
Serotype 7F
0.0
(0.0 to 0.043)
0.0
(0.0 to 0.043)
Serotype 14
0.0
(0.0 to 0.043)
0.047
(0.013 to 0.119)
Serotype 18C
0.0
(0.0 to 0.043)
0.012
(0.0 to 0.065)