Safety Study of GSK Biologicals' Rotavirus Vaccine (Rotarix®) Administered to Children Aged <1 Year in the United States

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00875641
• Collaborator: (none)
• Enrollment: 390,659
• Location: 1
• Actual Duration (Months): 90.5
• Patients Per Site Per Month: 4316

Study Details

Study Description

Brief Summary

This observational cohort study, conducted through two existing large administrative health databases in the US (outside the Vaccine Safety Datalink) is planned to confirm the safety profile regarding lack of any association of intussusception with Rotarix within 60 days of vaccination in a real life setting (routine use) in the US. This study will also include monitoring of Kawasaki disease, convulsions, hospitalizations due to acute lower respiratory tract infections and all-cause deaths within 60-days of vaccination.

This study involves three cohorts, one exposed and two control cohorts: infants who receive Rotarix (Exposed cohort) and infants who receive IPV vaccination (Unexposed cohort A and B).

This is a combined prospective and retrospective cohort study. Prospective component of the study identifies and compares study outcomes following Rotarix and IPV vaccination in the Exposed cohort and Unexposed cohort A, respectively.

Retrospective component of the study identifies and compares study outcomes following IPV vaccination in the Unexposed cohort B.

Condition or Disease	Intervention/Treatment	Phase
Infections, Rotavirus	Other: Health Insurance Database

Study Design

• Study Type: Observational
• Actual Enrollment: 390659 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Safety Study of GSK Biologicals' Rotarix® (Rotavirus Vaccine, Live, Oral) Administered to a Birth Cohort in United States Health Insurance Plans
• Actual Study Start Date: Apr 20, 2009
• Actual Primary Completion Date: Nov 4, 2016
• Actual Study Completion Date: Nov 4, 2016

Arms and Interventions

Arm	Intervention/Treatment
HRV cohort HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Other: Health Insurance Database; Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.
Concurrent Control cohort Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Other: Health Insurance Database; Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.
Recent Historical Control cohort Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.	Other: Health Insurance Database; Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.

Outcome Measures

Primary Outcome Measures

1. Incidence Rates of Intussusceptions (IS) Among the HRV Cohort and Comparator Cohorts [60 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

2. Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts [7 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

3. Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts [30 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

Secondary Outcome Measures

1. Incidence Rates of Kawasaki Disease Among the HRV Cohort and Comparator Cohorts [60 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

2. Incidence Rates of Convulsions Among the HRV Cohort and Comparator Cohorts [60 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

3. Incidence Rates of Acute Lower Respiratory Tract Infection (LRTI) Hospitalisation Among the HRV Cohort and Comparator Cohorts [60 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

4. Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts [7 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

5. Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts [30 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

6. Incidence Rates of All-cause Mortality Among the HRV Cohort and Comparator Cohorts [60 days following each vaccination]

   Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 1 Year
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

For Exposed cohort:

• Infants aged less than 1 year at study entry.

• Infants who are enrolled in one of the two participating health insurance plans databases within 30 days of birth.

• Have complete medical coverage and pharmacy benefits.

• Received at least one dose of Rotarix from 1 August 2008.

• Infants receiving Rotarix liquid formulation will also be eligible.

For Unexposed cohort A:

• Infants aged less than 1 year at study entry.

• Infants who are enrolled in one of the two participating health insurance plans databases within 30 days of birth.

• Have complete medical coverage and pharmacy benefits.

• Received at least one dose of IPV vaccine from 1 August 2008, with or without RotaTeq vaccination.

• Frequency-matched to the Rotarix cohort by gender, age at first vaccination (±1 week) and calendar quarter of vaccination within the same year.

For Unexposed cohort B:

• Infants who are enrolled in one of the two participating health insurance plans databases within 30 days of birth.

• Had complete medical coverage and pharmacy benefits.

• Received at least one dose of IPV vaccine.

• Vaccinated between 1 January 2006 (inclusive) and 31 July 2008 (inclusive).

• Not received any dose of rotavirus vaccination.

• Frequency-matched to the Rotarix cohort by gender, age at first vaccination (±1 week) and calendar quarter of vaccination.

Exclusion Criteria:

For Exposed cohort:

• Subject has received any dose of RotaTeq prior to the first Rotarix vaccine during the study period.

For Unexposed cohort A:

• Subject has received any dose of Rotarix prior to the first IPV vaccine during the study period.

For Unexposed cohort B:

• Subject has received any dose of rotavirus vaccines prior to the first IPV vaccine.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Waltham	Massachusetts	United States	02451

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00875641
• Other Study ID Numbers: 112229
• First Posted: Apr 3, 2009
• Last Update Posted: Jan 25, 2019
• Last Verified: Jun 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Rotavirus Infections

Study Results

Participant Flow

Recruitment Details	Subjects were identified through the automated corresponding health insurance plan databases, OptumInsight Life Sciences Research Database (from United Healthcare) and the HealthCore Integrated Research Database (HIRDSM) (part of Anthem, formerly known as WellPoint).

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Period Title: Overall Study
STARTED	57931	173384	159344
COMPLETED	57931	173384	159344
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort	Total
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.	Total of all reporting groups
Overall Participants	57931	173384	159344	390659
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	2.0 (0.7)	2.0 (0.7)	2.0 (0.7)	2.0 (0.7)
Sex: Female, Male (Count of Participants)
Female	27929 48.2%	83528 48.2%	77128 48.4%	188585 48.3%
Male	30002 51.8%	89856 51.8%	82216 51.6%	202074 51.7%
Race/Ethnicity, Customized (Count of Participants)
Northeast	8461 14.6%	18093 10.4%	22171 13.9%	48725 12.5%
South/Southeast	19875 34.3%	59167 34.1%	61965 38.9%	141007 36.1%
Midwest	17101 29.5%	51046 29.4%	41114 25.8%	109261 28%
West	12494 21.6%	45078 26%	34094 21.4%	91666 23.5%

Outcome Measures

1. Primary Outcome

Title	Incidence Rates of Intussusceptions (IS) Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	60 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-59 days, Any Dose	0.021	0.022	0.021
0-59 days, Dose 1	0.028	0.012	0.017
0-59 days, Dose 2	0.013	0.032	0.025

2. Primary Outcome

Title	Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	7 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-6 days, Any Dose	0.000	0.014	0.000
0-6 days, Dose 1	0.000	0.000	0.000
0-6 days, Dose 2	0.000	0.029	0.000

3. Primary Outcome

Title	Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	30 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-29 days, Any Dose	0.010	0.026	0.022
0-29 days, Dose 1	0.000	0.006	0.020
0-29 days, Dose 2	0.025	0.048	0.024

4. Secondary Outcome

Title	Incidence Rates of Kawasaki Disease Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	60 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-59 days, Any Dose	0.000	0.008	0.009
0-59 days, Dose 1	0.000	0.006	0.014
0-59 days, Dose 2	0.000	0.011	0.004

5. Secondary Outcome

Title	Incidence Rates of Convulsions Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	60 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-59 days, Any Dose	0.230	0.142	0.146
0-59 days, Dose 1	0.252	0.121	0.124
0-59 days, Dose 2	0.200	0.165	0.174

6. Secondary Outcome

Title	Incidence Rates of Acute Lower Respiratory Tract Infection (LRTI) Hospitalisation Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	60 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-59 days, Any Dose	1.518	1.320	1.669
0-59 days, Dose 1	1.696	1.529	2.008
0-59 days, Dose 2	1.278	1.079	1.260

7. Secondary Outcome

Title	Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	7 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-6 days, Any Dose	1.397	0.932	1.406
0-6 days, Dose 1	1.960	1.184	1.921
0-6 days, Dose 2	0.622	0.641	0.774

8. Secondary Outcome

Title	Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	30 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-29 days, Any Dose	1.593	1.383	1.788
0-29 days, Dose 1	1.858	1.523	2.166
0-29 days, Dose 2	1.228	1.221	1.327

9. Secondary Outcome

Title	Incidence Rates of All-cause Mortality Among the HRV Cohort and Comparator Cohorts
Description	Incidence rates were calculated following the first 2 doses of study vaccine as the number of events divided by the sum of the person-time in that risk period. Person-time was defined as the number of days at risk for the study outcomes. Person-time was calculated in months by dividing the number of person-days by (365.25/12).
Time Frame	60 days following each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on study population comprising of birth cohorts affiliated with 2 participating health insurance plans, United Healthcare & WellPoint, which were eligible for rotavirus vaccination according to routine recommendations. Within this population of infants, HRV, Concurrent Control & Recent Historical Control cohorts were defined.

Arm/Group Title	HRV Cohort	Concurrent Control Cohort	Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).	Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).	Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
Measure Participants	57931	173384	159344
0-59 days, Any Dose	0.048	0.045	0.062
0-59 days, Dose 1	0.047	0.059	0.075
0-59 days, Dose 2	0.050	0.029	0.045

Adverse Events

Arm/Group Title	HRV Cohort		Concurrent Control Cohort		Recent Historical Control Cohort
Arm/Group Description	HRV (Human Rotavirus) cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans within 30 days of birth and who received at least one dose of Rotarix vaccination as part of their normal health care (with no previous dose of RotaTeq prior to or concurrent with the first Rotarix vaccination).		Concurrent control cohort consisted of infants aged less than 1 year, enrolled in the participating health insurance plans, who were contemporaneous with the Rotarix vaccinees and who received at least one dose of IPV (Inactivated Poliovirus vaccine) with or without RotaTeq vaccination (with no previous dose of Rotarix prior to or concurrent with the first IPV vaccination).		Recent historical control cohort consisted of infants aged less than 1 year of age, enrolled in participating health insurance plans, vaccinated with at least one dose of IPV (Inactivated Poliovirus vaccine) between 1 January 2004 (OptumInsight) or 1 January 2006 (HealthCore) and 31 July 2008 and who did not receive any dose of rotavirus vaccination during the study period.
All Cause Mortality
	HRV Cohort		Concurrent Control Cohort		Recent Historical Control Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/57931 (0%)		27/173384 (0%)		33/159344 (0%)
Serious Adverse Events
	HRV Cohort		Concurrent Control Cohort		Recent Historical Control Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57931 (0%)		0/173384 (0%)		0/159344 (0%)
Other (Not Including Serious) Adverse Events
	HRV Cohort		Concurrent Control Cohort		Recent Historical Control Cohort
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57931 (0%)		0/173384 (0%)		0/159344 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.