A Study to Evaluate the Safety of FluMist in Healthy Children and Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study was to expand the data describing the safety profile of FluMist in the indicated populations (5-8, 9-17, and 18-49 years of age) and to assess the safety of annual revaccination in those who received FluMist in 2 or more consecutive years.

Detailed Description
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The primary objective of this study was to assess the safety of FluMist vaccination by comparing the rates of medically attended events (MAEs) (including serious adverse events [SAEs], anaphylaxis, urticaria, asthma, wheezing, pre-specified grouped diagnoses, and rare events potentially related to wild-type influenza) in FluMist recipients to rates in multiple non-randomized control groups.

Official Title
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Post-Marketing Evaluation of the Safety of Influenza Virus Vaccine Live, Intranasal (FluMist) in Healthy Children and Healthy Adults 5-49 Years of Age

Conditions
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Healthy

Intervention / Treatment
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* Biological: FluMist
* Biological: FluMist
* Biological: FluMist


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 5-49 years of age Members of the Kaiser Permanente (KP) Health Care Plan within KP of Northern California, KP of Colorado, and KP of Hawaii Exclusion Criteria: Must not have had any high risk underlying medical conditions, includig asthma

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 49 Years

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 |
| --- | --- |
| 1<br>5-8 years of age, estimated to be approximately 4,000 new FluMist vaccinees per season | Biological: FluMist<br>* Nasal Sprayer dose of FluMist with annual follow up<br>|
| 2<br>9-17 years of age, estimated to be approximately 5,000 new FluMist vaccinees per season | Biological: FluMist<br>* Nasal Sprayer dose of FluMist with annual follow up<br>|
| 3<br>18-49 years of age, estimated to be approximately 6,000 new FluMist vaccinees per season. | Biological: FluMist<br>* Nasal Sprayer dose of FluMist with annual follow up<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of Medically Attended Events (MAEs) Associated With a Significant Increased Risk in FluMist Recipients Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups | An MAE was defined as a coded medical diagnosis made by a health care provider and associated with a medical encounter (ie, a visit by a health plan member to a medical clinic or ED, or a hospital admission). Incident rate comparisons of MAEs with an identified increased risk associated with FluMist occurring in the same age group and setting across all three comparison groups, as these events are less likely to be due to chance alone. | 21 and 42 days | 
| Rates of MAEs Associated With a Significant Decreased Risk in FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups | Incident rate comparisons of MAEs with an identified decreased risk associated with FluMist occuring in the same age group and setting across all three comparison groups, as these events are less likely to be due to chance alone. All terms were analyzed for the entire population regardless of gender. | 21 and 42 days | 
| Rates of Anaphylaxis and Urticaria in FluMist Recipients Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups | Incident rate comparisons associated with a significantly increased risk in FluMist recipients compared to the within cohort control group for urticaria; there was no increased risk compared to the unvaccinated and TIV control groups and there were no anaphylaxis events that occurred within the 3-day risk period post vaccination. | 3 days | 
| Rates of MAEs Within the Pre-specified Grouped Diagnoses In The FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups. | There were no acute respiratory tract events, acute gastrointestinal tract events, or systemic bacterial infections with an identified increased or decreased risk associated with FluMist occuring in the same age group and setting across all three comparison groups. | 21 and 42 days | 
| Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the Within Cohort and Unvaccinated Control Groups | Incident rate comparisons associated with a significantly decreased risk in FluMist recipients compared to the within cohort control observed for all ages and 5-8 years of age within 21 days and compared to the unvaccinated control obseved for 18-49 years of age within 42 days. No asthma and wheezing incidence rate comparisons were significantly increased in FluMist recipients compared to the within cohort or unvaccinated control groups. | 21 and 42 days | 
| Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the TIV Control Group | Incident rate comparisons associated with a significantly decreased risk in FluMist recipients compared to the TIV control group for all ages, 5-8, 9-17, and 18-49 years of age. No asthma and wheezing incidence rate comparisons were significantly increased in FluMist recipients compared to the TIV control group. | 21 and 42 days | 
| Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the Unvaccinated Control Group | Incident rate comparisons associated with a significantly decreased risk in FluMist recipients compared to the unvaccinated control group for all ages, 5-8, and 9-17 years of age. No asthma and wheezing incidence rate comparisons were significantly increased in FluMist recipients compared to the unvaccinated control group. | 180 days | 
| Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the TIV Control Group | Incident rate comparisons associated with a significantly decreased risk in FluMist recipients compared to the TIV control group for all ages, 5-8, 9-17, and 18-49 years of age. No asthma and wheezing incidence rate comparisons were significantly increased in FluMist recipients compared to the TIV control group. | 180 days | 
| Rare Events Potentially Related to Wild-type Influenza in FluMist Recipients Compared to TIV and Unvaccinated Control Groups | Incident rate comparisons associated with a significantly decreased risk in FluMist recipients compared to TIV controls; there was no significantly decreased risk compared to the within cohort and unvaccinated controls. No MAEs potentially related to wild-type influenza were associated with a significantly increased risk in FluMist recipients. | 21 and 42 days | 
| Rates of Serious Adverse Events (SAEs) in FluMist Recipients Compared to Rates in Unvaccinated Control Group | Incident rate comparisons of SAEs with an identified decreased risk associated with FluMist compared to unvaccinated controls; no decreased risk was observed in compariosn to the within cohort control. There were no SAE incidence rate comparisons that were significantly increased in FluMist recipients. | 21 and 42 days | 
| Rates of SAEs in FluMist Recipients Compared to Rates in TIV Controls | Incident rate comparisons of SAEs with an identified decreased risk associated with FluMist compared to TIV controls. There were no SAE incidence rate comparisons that were significantly increased in FluMist recipients. | 21 and 42 days | 
| Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in Unvaccinated Controls | Incident rate comparisons of hospitalizations and deaths with an identified decreased risk associated with FluMist compared to unvaccinated controls. There were no hospitalization or death incidence rate comparisons that were significantly increased in FluMist recipients. | 180 days | 
| Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in TIV Controls | Incident rate comparisons of hospitalizations and deaths with an identified decreased risk associated with FluMist compared to TIV controls. There were no hospitalization or death incidence rate comparisons that were significantly increased in FluMist recipients. | 180 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rates of MAEs Associated With a Significant Decreased Risk in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in Within Cohort Controls | Incident rate comparisons of MAEs with an identified decreased risk in FluMist recipients receiving FluMist in 2 or more consecutive seasons compared to rates in within cohort controls within 21 days. There was no significant decreased risk in comparison to unvaccinated or TIV controls within the 21-day timeframe. | 21 days | 
| Rates of MAEs Associated With a Significant Increased Risk in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in Unvaccinated Controls | Incident rate comparisons of MAEs with an identified increased risk in FluMist recipients receiving FluMist in 2 or more consecutive seasons compared to rates in unvaccinated recipients. There was no increased risk at 3 or 21 days and there was no increased risk compared to the Within Cohort or TIV control groups. | 42 days | 
| Rates of MAEs Associated With a Significant Decreased Risk in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in TIV Controls Within 42 Days | Incident rate comparisons of MAEs with an identified decreased risk in FluMist recipients receiving FluMist in 2 or more consecutive seasons compared to rates in TIV recipients within 42 days. There was no significant decreased risk in comparison to unvaccinated controls within the 42-day timeframe. | 42 days | 
| Rates of MAEs Associated With a Significant Decreased Risk Within 180 Days in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in Unvaccinated Controls | Incident rate comparisons of MAEs within 180 days with an identified decreased risk associated with FluMist recipients compared to Unvaccinated Controls. There were no MAE incidence rate comparisons that were significantly increased in FluMist recipients compared to Unvaccinated Controls. | 180 days | 
| Rates of MAEs Associated With a Significant Decreased Risk Within 180 Days in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in TIV Controls | Incident rate comparisons of MAEs within 180 days with an identified decreased risk associated with FluMist recipients compared to TIV recipients. There were no MAE incidence rate comparisons that were significantly increased in FluMist recipients compared to TIV recipients. | 180 days | 
| Rates of SAEs and Hospitalizations or Deaths Within 180 Days in the Subset of Individuals Who Received FluMist in 2 or More Consecutive Years Compared to Rates in Unvaccinated and TIV Controls | Incident rate comparisons of SAEs and hospitalizations or deaths with an identified decreased risk associated with FluMist recipients compared to TIV recipients; there were no significant decreases compared to the unvaccinated controls. There were no SAE and hospitalization or death incidence rate comparisons that were significantly increased in FluMist recipients compared to their controls. | 180 days | 
| Rates of Solicited Adverse Events in Subsets of FluMist Recipients During the First Year of the Trial (2003-2004 Influenza Season) |  | Within 2-3 days of vaccination | 
| Rates of Solicited Adverse Events in Subsets of FluMist Recipients During the First Year of the Trial (2003-2004 Influenza Season) |  | Within 14 days of vaccination |