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

Study Overview
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Brief Summary
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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.

Official Title
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Safety Study of GSK Biologicals' Rotarix® (Rotavirus Vaccine, Live, Oral) Administered to a Birth Cohort in United States Health Insurance Plans

Conditions
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Infections, Rotavirus

Intervention / Treatment
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* Other: Health Insurance Database


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Maximum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HRV cohort<br>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<br>* Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.<br>|
| Concurrent Control cohort<br>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<br>* Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.<br>|
| Recent Historical Control cohort<br>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<br>* Review of two health insurance databases in the US to determine the safety outcomes among infants who have received Rotarix or IPV vaccination.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Rates of Intussusceptions (IS) Among the HRV Cohort and Comparator Cohorts | 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). | 60 days following each vaccination | 
| Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts | 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). | 7 days following each vaccination | 
| Incidence Rates of IS Among the HRV Cohort and Comparator Cohorts | 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). | 30 days following each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence Rates of Kawasaki Disease Among the HRV Cohort and Comparator Cohorts | 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). | 60 days following each vaccination | 
| Incidence Rates of Convulsions Among the HRV Cohort and Comparator Cohorts | 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). | 60 days following each vaccination | 
| Incidence Rates of Acute Lower Respiratory Tract Infection (LRTI) Hospitalisation Among the HRV Cohort and Comparator Cohorts | 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). | 60 days following each vaccination | 
| Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts | 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). | 7 days following each vaccination | 
| Incidence Rates of Acute LTRI Hospitalisation Among the HRV Cohort and Comparator Cohorts | 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). | 30 days following each vaccination | 
| Incidence Rates of All-cause Mortality Among the HRV Cohort and Comparator Cohorts | 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). | 60 days following each vaccination |