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

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00113880
Collaborator
(none)
63,061
Enrollment
77
Locations
80
Duration (Months)
819
Patients Per Site
10.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: FluMist
  • Biological: FluMist
  • Biological: FluMist

Detailed Description

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.

Study Design

Study Type:
Observational
Actual Enrollment :
63061 participants
Observational Model:
Cohort
Time Perspective:
Prospective
Official Title:
Post-Marketing Evaluation of the Safety of Influenza Virus Vaccine Live, Intranasal (FluMist) in Healthy Children and Healthy Adults 5-49 Years of Age
Study Start Date :
Oct 1, 2003
Actual Primary Completion Date :
Sep 1, 2008
Actual Study Completion Date :
Jun 1, 2010

Arms and Interventions

Arm Intervention/Treatment
1

5-8 years of age, estimated to be approximately 4,000 new FluMist vaccinees per season

Biological: FluMist
Nasal Sprayer dose of FluMist with annual follow up
2

9-17 years of age, estimated to be approximately 5,000 new FluMist vaccinees per season

Biological: FluMist
Nasal Sprayer dose of FluMist with annual follow up
3

18-49 years of age, estimated to be approximately 6,000 new FluMist vaccinees per season.

Biological: FluMist
Nasal Sprayer dose of FluMist with annual follow up

Outcome Measures

Primary Outcome Measures

  1. 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 [21 and 42 days]

    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.

  2. Rates of MAEs Associated With a Significant Decreased Risk in FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups [21 and 42 days]

    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.

  3. Rates of Anaphylaxis and Urticaria in FluMist Recipients Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups [3 days]

    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.

  4. Rates of MAEs Within the Pre-specified Grouped Diagnoses In The FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups. [21 and 42 days]

    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.

  5. Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the Within Cohort and Unvaccinated Control Groups [21 and 42 days]

    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.

  6. Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the TIV Control Group [21 and 42 days]

    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.

  7. Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the Unvaccinated Control Group [180 days]

    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.

  8. Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the TIV Control Group [180 days]

    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.

  9. Rare Events Potentially Related to Wild-type Influenza in FluMist Recipients Compared to TIV and Unvaccinated Control Groups [21 and 42 days]

    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.

  10. Rates of Serious Adverse Events (SAEs) in FluMist Recipients Compared to Rates in Unvaccinated Control Group [21 and 42 days]

    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.

  11. Rates of SAEs in FluMist Recipients Compared to Rates in TIV Controls [21 and 42 days]

    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.

  12. Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in Unvaccinated Controls [180 days]

    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.

  13. Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in TIV Controls [180 days]

    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.

Secondary Outcome Measures

  1. 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 [21 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 within cohort controls within 21 days. There was no significant decreased risk in comparison to unvaccinated or TIV controls within the 21-day timeframe.

  2. 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 [42 days]

    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.

  3. 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 [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.

  4. 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 [180 days]

    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.

  5. 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 [180 days]

    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.

  6. 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 [180 days]

    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.

  7. 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]

  8. 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:
5 Years to 49 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Kaiser Permanente Pediatrics Alameda California United States 94501
2 Kaiser Permanente Pediatrics Antioch California United States 94509
3 Kaiser Permanente Pediatrics Clovis California United States 93611
4 Kaiser Permanente Pediatrics Daly City California United States 94015
5 Kaiser Permanente Davis California United States 95616
6 Kaiser Pediatric Injections Fairfield California United States 94533
7 Kaiser Permanente-Pediatrics Folsom California United States 95630
8 Kaiser Permanente Adult Injection Fremont California United States 94538
9 Kaiser Permanente Pediatrics Fremont California United States 94543
10 Kaiser Permanente Pediactrics Fresno California United States 93726
11 Kaiser Permanente Pediatrics Gilroy California United States 93726
12 Kaiser Pediatric Injection Station Hayward California United States 94545
13 Kaiser Permanente Lincoln California United States 95648
14 Kaiser Pediatric Injection Station Livermore California United States 94551
15 Kaiser Permanente Injection Clinic Manteca California United States 95337
16 Kaiser Permanente Pediatrics Martinez California United States 94553
17 Kaiser Permanente Adult Medicine Milpitas California United States 95035
18 Kaiser Permanente Employee Health Milpitas California United States 95035
19 Kaiser Permanente Pediatrics Milpitas California United States 95035
20 Kaiser Permanente Injection Clinic Modesto California United States 95356
21 Kaiser Permanente Medicine Dept. Modesto California United States 95356
22 Kaiser Permanente Pediatrics Mountain View California United States 95356
23 Kaiser Permanente Pediatrics Napa California United States 94558
24 Kaiser Permanente Pediatrics Novato California United States 94945
25 Kaiser Permanente Employee Health Oakland California United States 94611
26 Kaiser Permanente Injection Clinic Oakland California United States 94611
27 Kaiser Permanente Pediatrics Oakland California United States 94611
28 Kaiser Permanente Regional Employee Health Oakland California United States 94612
29 Kaiser Permanente Pediatrics Petaluma California United States 94954
30 Kaiser Permanente Pediatrics Pleasanton California United States 94588
31 Kaiser Permanente Pediatrics Rancho Cordova California United States 95670
32 Kaiser Permanente Redwood City California United States 94063
33 Kaiser Permanente Adult Injection Clinic Richmond California United States 94804
34 Kaiser Permanente Pediatrics Richmond California United States 94804
35 Kaiser Permanente Pediatrics Roseville California United States 95661
36 Kaiser Permanente Roseville California United States 95661
37 Kaiser Permanente, Point West Clinic Pediatric Injection Sacramento California United States 95815
38 Kaiser Permanente Sacramento California United States 95815
39 Kaiser Pediatric Injection Station Sacramento California United States 95823
40 Kaiser Permanente Medicine Dept. Sacramento California United States 95823
41 Kaiser Permanente Medicine Dept. San Francisco California United States 94115
42 Kaiser Permanente Pediatrics San Francisco California United States 94115
43 Kaiser Permanente Pharmacy San Francisco California United States 94115
44 Kaiser Pediatric Adult Medicine San Jose California United States 95199
45 Kaiser Pediatric Injection Clinic San Jose California United States 95199
46 Kaiser Permanente Employee Health San Rafael California United States 94115
47 Kaiser Permanente Pediatrics San Rafael California United States 94901
48 Kaiser Permanente Adult Medicine Santa Clara California United States 95051
49 Kaiser Permanente Employee Health Santa Rosa California United States 95403
50 Kaiser Permanente Pediatrics Santa Rosa California United States 95403
51 Kaiser Permanente Pediatrics Selma California United States 93662
52 Kaiser Permanente Injection/Allergy Stockton California United States 95210
53 Kaiser Permanente Pediatrics Tracy California United States 95376
54 Kaiser Pediatric Injection Room Vacaville California United States 95688
55 Kaiser Permanente Adult Medicine Vacaville California United States 95688
56 Kaiser Permanente Injection Clinic Vallejo California United States 94589
57 Kaiser Permanente Pediatric Injections Vallejo California United States 94589
58 Kaiser Permanente Pediatrics Walnut Creek California United States 94596
59 Kaiser Permanente Pediatrics Walnut Creek California United States 94598
60 Kaiser Permanente, Hidden Lake Arvada Colorado United States 80003
61 Kaiser Permanente, Aurora Centrepoint Aurora Colorado United States 80012
62 Kaiser Permanente, Smoky Hill Aurora Colorado United States 80015
63 Kaiser Permanente, Baseline Boulder Colorado United States 80302
64 Kaiser Permanente, Boulder Boulder Colorado United States 80304
65 Kaiser Permanente, Broomfield Broomfield Colorado United States 80020
66 Kaiser Permanente, Skyline Denver Colorado United States 80205
67 Kaiser Permanente, East Denver Colorado United States 80231
68 Kaiser Permanente, Englewood Englewood Colorado United States 80110
69 Kaiser Permanente Highlands Ranch Colorado United States 80129
70 Kaiser Permanente Lafayette Colorado United States 80026
71 Kaiser Permanente, Lakewood Lakewood Colorado United States 80226
72 Kaiser Permanente Arapahoe Littleton Colorado United States 80122
73 Kaiser Permanente, Southwest Littleton Colorado United States 80123
74 Kaiser Permanente, Ken Caryl Littleton Colorado United States 80127
75 Kaiser Permanente, Longmont Primary Care Longmont Colorado United States 80501
76 Kaiser Permanente, Westminster Westminster Colorado United States 80234
77 Kaiser Permanente, Wheatridge Wheatridge Colorado United States 80033

Sponsors and Collaborators

  • MedImmune LLC

Investigators

  • Study Director: Christopher Ambrose, M.D., MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00113880
Other Study ID Numbers:
  • FM025
First Posted:
Jun 13, 2005
Last Update Posted:
Jan 8, 2013
Last Verified:
Dec 1, 2012

Study Results

Participant Flow

Recruitment Details Subjects 5 to 49 years of age who were members of the Kaiser Permanente (KP) Health Care Plan at health care centers in Northern California, Colorado, and Hawaii. The first subject vaccinated with FluMist was on 15Oct2003 and the date of the last subject/last assessment was 30Sep2008.
Pre-assignment Detail Of 197,502 subjects, 189,174 unique subjects were included in this study, representing the total number of subjects who were defined exclusively within each season. FluMist recipients who received an additional 7,570 FluMist doses were excluded from the analysis based on the presence of high risk underlying medical conditions and other factors.
Arm/Group Title FluMist Recipients Unvaccinated Control TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the KP Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Period Title: Overall Study
STARTED 63061 71949 62492
COMPLETED 63061 71949 62492
NOT COMPLETED 0 0 0

Baseline Characteristics

Arm/Group Title FluMist Recipients Unvaccinated Control TIV-Vaccinated Control Total
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the KP Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California). Total of all reporting groups
Overall Participants 63061 71949 62492 197502
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
17.1
(12.8)
17.1
(12.8)
16.8
(12.7)
17.1
(12.8)
Gender (dose) [Number]
Female
41593
41591
37373
120557
Male
33116
33115
29626
95857

Outcome Measures

1. Primary Outcome
Title 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
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). Significance was observed in the clinic setting, 21 days post Dose 1 in 7 subjects (breast lump/cyst, 9-17 yrs) and in 22 subjects (mastitis, 18-49 yrs).
Arm/Group Title FluMist Recipients Within Cohort Control Unvaccinated Control TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 63061 71949 62492
Measure Doses 74709 74709 74706 66999
Breast lump/cyst
0.33
0.00
0.00
0.00
Mastitis
1.46
0.61
0.20
0.23
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Breast lump/cyst event rates were presented per 1,000 person-months. If the control group has no event, the relative risk (RR) or hazard ratio (HR) is not estimable.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Exact method or Cox model
Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Unvaccinated Control
Comments Breast lump/cyst event rates were presented per 1,000 person-months. If the control group has no event, the RR or HR is not estimable.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Exact method or Cox model
Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, TIV-Vaccinated Control
Comments Breast lump/cyst event rates were presented per 1,000 person-months. If the control group has no event, the RR or HR is not estimable.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Exact method or Cox model
Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Mastitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.59
Confidence Interval (2-Sided) 95%
0.64 to 3.92
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Unvaccinated Control
Comments Mastitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 7.35
Confidence Interval (2-Sided) 95%
2.20 to 24.54
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, TIV-Vaccinated Control
Comments Mastitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 7.17
Confidence Interval (2-Sided) 95%
2.13 to 24.13
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title Rates of MAEs Associated With a Significant Decreased Risk in FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (1 or 2 for ages 5-8 years). Significance observed in the clinic, 21 days post Dose 1 in 1 subj. (heart murmur, all ages combined); 18 and 19 subj.(pregnancy exam, 18-49 and all ages combined).
Arm/Group Title FluMist Recipients Within Cohort Control Unvaccinated Control TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 63061 71949 62492
Measure Doses 74709 74709 74706 66999
Heart murmur
0.02
0.16
0.15
0.21
Pregnancy exam, 18-49 yrs
1.19
3.06
23.48
70.41
Pregnancy exam, all ages combined
0.37
0.89
7.18
20.09
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Heart murmur event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.03
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.00 to 0.79
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Unvaccinated Control
Comments Heart murmur event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.13
Confidence Interval (2-Sided) 95%
0.02 to 1.00
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, TIV-Vaccinated Control
Comments Heart murmur event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.11
Confidence Interval (2-Sided) 95%
0.01 to 0.86
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Pregnancy exam/supervision event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.20 to 0.70
Parameter Dispersion Type:
Value:
Estimation Comments Population was the 18-49 year age group.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Pregnancy exam/supervision event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.22 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments Population was the all ages combined group.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Unvaccinated Control
Comments Pregnancy exam/supervision event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.03 to 0.08
Parameter Dispersion Type:
Value:
Estimation Comments Population was the 18-49 year age and the all ages combined groups.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, TIV-Vaccinated Control
Comments Pregnancy exam/supervision event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
0.01 to 0.03
Parameter Dispersion Type:
Value:
Estimation Comments Population was the 18-49 year age and all ages combined groups.
3. Primary Outcome
Title Rates of Anaphylaxis and Urticaria in FluMist Recipients Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups
Description 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.
Time Frame 3 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (3 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years).
Arm/Group Title FluMist Recipients Within Cohort Control Unvaccinated Control TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 63061 71949 62492
Measure Doses 74709 74709 74706 66999
Number [Cases per 1,000 person-months]
1.19
0.89
0.83
1.58
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Urticaria event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 2.06
Confidence Interval (2-Sided) 95%
1.02 to 4.13
Parameter Dispersion Type:
Value:
Estimation Comments
4. Primary Outcome
Title Rates of MAEs Within the Pre-specified Grouped Diagnoses In The FluMist Group Compared to Rates in Within Cohort, Unvaccinated, and TIV Control Groups.
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years).
Arm/Group Title FluMist Recipients Within Cohort Control Unvaccinated Control TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California). Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 63061 71949 62492
Measure Doses 74709 74709 74706 66999
Number [Cases per 1,000 person-months]
0
0
0
0
5. Primary Outcome
Title Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the Within Cohort and Unvaccinated Control Groups
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). Significance was observed across all settings, post Dose 1 within 21 days for within cohort and within 42 days for unvaccinated.
Arm/Group Title FluMist Recipients Within Cohort Control Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 63061 71949
Measure Doses 74709 74709 74706
Any asthma or wheezing event, all ages, 21 d
2.42
3.42
2.52
Any asthma or wheezing event, 21 d, 5-8
3.28
5.59
3.03
Any asthma or wheezing event, 42 d, 18-49
1.48
NA
2.18
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.56 to 0.89
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages combined within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.41 to 0.83
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Unvaccinated Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.46 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in unvaccinated controls represents the denominator.
6. Primary Outcome
Title Rates of Asthma and Wheezing Within 21 and 42 Days in FluMist Recipients Compared to Rates in the TIV Control Group
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). Significance was observed across all settings, post Dose 1 within 21 days and 42 days (all age groups) and post Dose 2 (PD2) within 42 days (5-8 yrs).
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Any asthma or wheezing event, 21 d, all ages
2.30
3.20
Any asthma or wheezing event, 21 d, 5-8
3.07
10.07
Any asthma or wheezing event, 21 d, 9-17
2.43
7.15
Any asthma or wheezing event, 21 d, 18-49
1.24
2.94
Any asthma or wheezing event, 42 d, all ages
2.76
7.23
Any asthma or wheezing event, 42 d, 5-8
4.11
10.28
Any asthma or wheezing event, 42 d, 9-17
2.70
7.57
Any asthma or wheezing event, 42 d, 18-49
1.37
3.37
Any asthma or wheezing event, 42 d, PD2, 5-8
7.10
14.99
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.27 to 0.41
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages combined within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
0.22 to 0.42
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.24 to 0.47
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.23 to 0.75
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.33 to 0.44
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages combined within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.32 to 0.50
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.28 to 0.45
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.27 to 0.60
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.21 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years, PD2 within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
7. Primary Outcome
Title Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the Unvaccinated Control Group
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (180 days), age group (5-8, 9-17, 18-49 yrs), setting (clinic, hospital, or ED), and number of doses (1 or 2 for 5-8 yrs). Significance was observed for asthma/reactive airway disease (RAD) and any ashtma or wheezing event across all settings, PD1 (all ages and 9-17 yrs) and PD2 (5-8 yrs).
Arm/Group Title FluMist Recipients Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 71949
Measure Doses 74709 74706
Any asthma or wheezing event, PD1, all ages
4.07
4.45
Any asthma or wheezing event, PD1, 9-17
4.00
4.81
Asthma/RAD, PD1, all ages
3.04
3.48
Asthma/RAD, PD1, 9-17
3.10
3.94
Asthma/RAD, PD2, 5-8
2.69
5.54
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.92
Confidence Interval (2-Sided) 95%
0.86 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages combined, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.75 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 yrs., within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.81 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments Population: All ages, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.79
Confidence Interval (2-Sided) 95%
0.70 to 0.88
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.29 to 0.79
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8yrs, within 180 days, PD2. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
8. Primary Outcome
Title Rates of Asthma and Wheezing Within 180 Days in FluMist Recipients Compared to Rates in the TIV Control Group
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (180 days), age group (5-8, 9-17, 18-49 yrs), setting (clinic, hospital, or ED), and number of doses (1 or 2 for 5-8 yrs). Significance was observed for asthma/RAD, wheezing/shortness of breath (SOB), and any ashtma or wheezing event across all settings, PD1 (all age groups) and PD2.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Any asthma or wheezing event, PD1, all ages
4.06
8.50
Any asthma or wheezing event, PD1, 5-8
5.88
11.45
Any asthma or wheezing event, PD1, 9-17
3.96
9.41
Any asthma or wheezing event, PD1, 18-49
2.27
3.98
Any asthma or wheezing event, PD2, 5-8
5.76
11.40
Asthma/RAD, PD1, all ages
3.04
7.23
Asthma/RAD, PD1, 5-8
3.87
9.14
Asthma/RAD, PD1, 9-17
3.08
8.25
Asthma/RAD, PD1, 18-49
2.10
3.65
Asthma/RAD, PD2, 5-8
2.18
7.67
Wheezing/SOB, PD1, all ages
1.15
1.53
Wheezing/SOB, PD1, 5-8
2.29
2.77
Wheezing/SOB, PD1, 9-17
0.98
1.37
Wheezing/SOB, PD1, 18-49
0.19
0.41
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.45 to 0.51
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages combined, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.47 to 0.56
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.38 to 0.46
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.49 to 0.67
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.33 to 0.76
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 yrs, within 180 days, PD2. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.39 to 0.45
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.38 to 0.47
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.34 to 0.41
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.05
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.49 to 0.68
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/Rad event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.15 to 0.52
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 yrs, within 180 days, PD2. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Wheezing/SOB event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.66 to 0.85
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Wheezing/SOB event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.70 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Wheezing/SOB event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.58 to 0.88
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Wheezing/SOB event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.27 to 0.78
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 180 days, PD1. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
9. Primary Outcome
Title Rare Events Potentially Related to Wild-type Influenza in FluMist Recipients Compared to TIV and Unvaccinated Control Groups
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). significance was observed for encephalitis/encephalopathy, for all age groups, across all settings within 42 days, PD1.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control Unvaccinated Controls
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California). Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492 71949
Measure Doses 74709 66999 74706
Number [Cases per 1,000 person-months]
0.00
0.05
0.00
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Encephalitis/encephalopathy event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 0.82
Parameter Dispersion Type:
Value:
Estimation Comments The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
10. Primary Outcome
Title Rates of Serious Adverse Events (SAEs) in FluMist Recipients Compared to Rates in Unvaccinated Control Group
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). Significance was observed in the any/death setting, 21 and 42 days post Dose 1, for all ages and 18-49.
Arm/Group Title FluMist Recipients Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 71949
Measure Doses 74709 74706
Any SAE, all ages, 21 days
1.12
1.72
Any SAE, 18-49, 21 days
1.33
3.85
Any SAE, all ages, 42 days
0.98
1.64
Any SAE, 18-49, 42 days
1.28
3.87
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.47 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.21 to 0.57
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.47 to 0.77
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.23 to 0.48
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
11. Primary Outcome
Title Rates of SAEs in FluMist Recipients Compared to Rates in TIV Controls
Description 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.
Time Frame 21 and 42 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (21 and 42 days), age group (5-8, 9-17, 18-49 years of age), setting (clinic, hospital, or ED), and number of doses (one or two for ages 5-8 years). Significance was observed in the any/death setting, 21 and 42 days post Dose 1, for all ages and 18-49.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Any SAE, all ages, 21 days
1.12
0.00
Any SAE, 18-49, 21 days
1.33
0.00
Any SAE, all ages, 42 days
0.98
0.23
Any SAE, 18-49, 42 days
1.28
0.23
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.47 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.21 to 0.57
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 21 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.47 to 0.77
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments SAE event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.23 to 0.48
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
12. Primary Outcome
Title Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in Unvaccinated Controls
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (180 days), age group (5-8, 9-17, 18-49 years of age), and number of doses (one or two for ages 5-8 years). Significance was observed in the hospitalization/death setting, 180 days post Dose 1, for all ages and 18-49.
Arm/Group Title FluMist Recipients Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 71949
Measure Doses 74709 74706
Any hosp. or death, all ages
0.97
1.49
Any hosp. or death, 18-49
1.46
3.36
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.64
Confidence Interval (2-Sided) 95%
0.57 to 0.73
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.36 to 0.51
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
13. Primary Outcome
Title Rates of Hospitalizations and Deaths Within 180 Days in FluMist Recipients Compared to Rates in TIV Controls
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (180 days), age group (5-8, 9-17, 18-49 years of age), and number of doses (one or two for ages 5-8 years). Significance was observed in the hospital/death setting 180 days post Dose 1, for all ages and 18-49.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Any hosp or death, all ages
0.95
3.12
Any hosp or death, 18-49
1.46
9.10
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.26 to 0.33
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.13 to 0.18
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
14. Secondary Outcome
Title 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
Description 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.
Time Frame 21 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (3, 21, and 42 days), age group (5-8, 9-17, 18-49 years of age), and setting (clinic, hospital, or ED), post Doe 1. FluMist recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance observed across all settings.
Arm/Group Title FluMist Recipients Within Cohort Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. FluMist recipients served as their own controls based on the observation time after vaccination. FluMist vaccinated cohort served as its own control. In the primary analyses using within-cohort controls, "risk" periods of Days 0 to 3 and Days 0 to 21 post vaccination were compared to "reference" observation time occurring after the respective risk periods, ie, Days 4 to 42 for the risk period of Days 0 to 3 and Days 22 to 42 for the risk period of Days 0 to 21.
Measure Participants 63061 63061
Measure Doses 74709 74709
Sinusitis, 18-49
2.57
7.03
URI, all ages
10.24
14.79
URI, 9-17
19
38
URI, 9-17
7.26
14.90
URI, 18-49
11.16
15.86
Any acute resp. tract event, all ages
29.20
37.45
Any acute resp. tract event , 9-17
23.03
33.15
Any acute resp. tract event ,18-49
21.54
30.09
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Sinusitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.16
Confidence Interval (2-Sided) 95%
0.03 to 0.93
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments URI event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.60
Confidence Interval (2-Sided) 95%
0.40 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments URI event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.28 to 0.84
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments URI event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.10 to 0.78
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any acute resp. tract event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.63 to 0.96
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any acute resp. tract event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.03
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.50 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any acute resp. tract event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.41
Confidence Interval () 95%
0.21 to 0.79
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years, within 21 days. The rate of events during the risk period represents the numerator; the rate of events during the control period represents the denominator.
15. Secondary Outcome
Title 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
Description 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.
Time Frame 42 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (3, 21, and 42 days), age group (5-8, 9-17, 18-49 years of age), and setting (clinic, hospital, or ED), post Doe 1. FluMist recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance observed across all settings.
Arm/Group Title FluMist Recipients Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 71949
Measure Doses 74709 74706
Sinusitis, all ages, 42 days
3.74
1.92
IBS, all ages, 42 days
0.57
0.77
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Sinusitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.95
Confidence Interval (2-Sided) 95%
1.14 to 3.34
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Irritable bowel syndrome event rates were presented per 1,000 person-months. If the control group has no event, the RR or HR is not estimable.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Exact method or Cox model
Comments
16. Secondary Outcome
Title 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
Description 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.
Time Frame 42 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (3, 21, and 42 days), age group (5-8, 9-17, 18-49 years of age), and setting (clinic, hospital, or ED), post Doe 1. FluMist recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance observed across all settings.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Asthma/RAD, all ages
1.22
3.87
Asthma/RAD, 5-8
1.82
5.11
Asthma/RAD, 9-17
1.43
4.28
Pharyngitis, all ages
8.18
11.06
Pharyngitis, 18-49
2.77
7.42
Any acute resp. tract event, all ages
30.72
36.86
Any acute resp. tract event , 9-17
24.81
34.06
Any asthma or wheezing event, all ages
2.04
5.31
Any asthma or wheezing event, 9-17
2.04
5.92
Any asthma or wheezing event,18-49
0.00
2.31
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
0.15 to 0.57
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.03
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.12 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.13 to 0.74
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Pharyngitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.55 to 0.99
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Pharyngitis event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.04
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.14 to 0.93
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any acute respiratory tract event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.71 to 0.97
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any acute respiratory tract event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.57 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.22 to 0.61
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.33
Confidence Interval (2-Sided) 95%
0.16 to 0.68
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.03
Comments
Method Fisher Exact
Comments
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
0.00 to 0.82
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49, within 42 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
17. Secondary Outcome
Title 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
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (180 days), age group (5-8, 9-17, 18-49 years of age), and setting (clinic, hospital, or ED), post Doe 1. FluMist recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance observed across all settings.
Arm/Group Title FluMist Recipients Unvaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. Non-randomized unvaccinated subjects were matched 1:1 with FluMist recipients and were selected from the pool of individuals who were members of the Kaiser Health Maintenance Organization (HMO) during the same month that the reference FluMist recipient was vaccinated, and included only those who did not receive the trivalent inactivated influenza vaccine (TIV) formulation at the Kaiser HMO. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, emergency department (ED), and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 71949
Measure Doses 74709 74706
Asthma/RAD, all ages
2.88
3.98
Asthma/RAD, 9-17
3.11
4.63
Any asthma or wheezing event, all ages
3.70
4.93
Any asthma or wheezing event, 9-17
3.80
5.25
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.58 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.67
Confidence Interval (2-Sided) 95%
0.49 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.61 to 0.92
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.69
Confidence Interval (2-Sided) 95%
0.52 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the unvaccinated controls represents the denominator.
18. Secondary Outcome
Title 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
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses performed by period (180 days), age group (5-8, 9-17, 18-49 years of age), and setting (clinic, hospital, or ED), post Doe 1. FluMist recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance observed across all settings.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Asthma/RAD, all ages
2.80
6.77
Asthma/RAD, 5-8
3.19
8.49
Asthma/RAD, 9-17
3.09
7.37
Asthma/RAD, 18-49
1.64
3.29
Any asthma or wheezing event, all ages
3.62
7.95
Any asthma or wheezing event, 5-8
4.86
9.94
Any asthma or wheezing event, 9-17
3.82
8.83
Any asthma or wheezing event,18-49
1.64
3.51
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.41
Confidence Interval (2-Sided) 95%
0.33 to 0.51
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.37
Confidence Interval (2-Sided) 95%
0.26 to 0.55
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.31 to 0.56
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Asthma/RAD event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.02
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.26 to 0.91
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.45
Confidence Interval () 95%
0.37 to 0.55
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.35 to 0.67
Parameter Dispersion Type:
Value:
Estimation Comments Population: 5-8 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.43
Confidence Interval (2-Sided) 95%
0.33 to 0.56
Parameter Dispersion Type:
Value:
Estimation Comments Population: 9-17 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Any asthma or wheezing event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.25 to 0.85
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 years, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
19. Secondary Outcome
Title 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
Description 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.
Time Frame 180 days

Outcome Measure Data

Analysis Population Description
Analyses were performed by period (180 days) and age group (5-8, 9-17, 18-49 years of age), post Dose 1. recipients who were part of the main analysis and received FluMist in both the current and the immediate prior season(s) were included in this analysis. Significance was observed for any hospitalization or death, for all ages and 18-49.
Arm/Group Title FluMist Recipients TIV-Vaccinated Control
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist, while subjects ≥ 9 years of age were expected to receive only 1 dose. TIV-Vaccinated Control Non-randomized TIV-vaccinated subjects matched 1:1 with FluMist recipients and were selected from the pool of individuals who received TIV but not FluMist at the Kaiser HMO during the same month that the reference FluMist recipient was vaccinated. Other matching factors included age (within 1 year), gender, prior year health care utilization level (ie, similar number of hospital, ED, and clinic visits), and medical center (only for subjects from Northern California).
Measure Participants 63061 62492
Measure Doses 74709 66999
Any hosp or death, all ages
0.91
1.93
Any hosp or death, 18-49
1.75
5.50
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple confidence intervals (CIs) were constructed without multiplicity adjustment.
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.32 to 0.69
Parameter Dispersion Type:
Value:
Estimation Comments Population: all ages, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FluMist Recipients, Within Cohort Control
Comments Hospitalization or death event rates were presented per 1,000 person-months.
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value 0.01
Comments Due to the exploratory nature of the study and the lack of formal hypothesis testing, multiple CIs were constructed without multiplicity adjustment
Method Regression, Cox
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.17 to 0.54
Parameter Dispersion Type:
Value:
Estimation Comments Population: 18-49 yrs, within 180 days. The rate of events in FluMist recipients represents the numerator; the rate of events in the TIV controls represents the denominator.
20. Secondary Outcome
Title Rates of Solicited Adverse Events in Subsets of FluMist Recipients During the First Year of the Trial (2003-2004 Influenza Season)
Description
Time Frame Within 2-3 days of vaccination

Outcome Measure Data

Analysis Population Description
Subsets of FluMist recipients 5-8, 9-17, and 18-49 years of age
Arm/Group Title FluMist Recipients (5-8 Years Old) FluMist Recipients (9-17 Years Old) FluMist Recipients (18-49 Years Old)
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist. Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects ≥ 9 years of age were expected to receive only 1 dose. Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects ≥ 9 years of age were expected to receive only 1 dose.
Measure Participants 749 683 643
Fever
8.3
6.1
6.8
Runny nose
34.3
30.3
41.7
Cough
17.6
11.4
13.1
Sore throat
9.5
9.0
20.9
Irritability
5.9
4.4
6.8
Headache
9.2
15.2
21.7
Chillls
3.6
4.2
7.8
Vomiting
2.3
1.3
0.8
Muscle aches
4.3
5.2
12.7
Fatigue
10.8
12.9
18.1
21. Secondary Outcome
Title Rates of Solicited Adverse Events in Subsets of FluMist Recipients During the First Year of the Trial (2003-2004 Influenza Season)
Description
Time Frame Within 14 days of vaccination

Outcome Measure Data

Analysis Population Description
Subsets of FluMist recipients 5-8, 9-17, and 18-49 years of age
Arm/Group Title FluMist Recipients (5-8 Years Old) FluMist Recipients (9-17 Years Old) FluMist Recipients (18-49 Years Old)
Arm/Group Description Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects from 5-8 years of age may have received 1 or 2 doses of FluMist. Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects ≥ 9 years of age were expected to receive only 1 dose. Subjects who had been immunized with FluMist as part of routine clinical practice at health care centers within the Kaiser Permanente Health Care Plan. Subjects ≥ 9 years of age were expected to receive only 1 dose.
Measure Participants 749 683 643
Fever
13.4
11.0
7.7
Runny nose
38.2
33.4
38.6
Cough
25.6
18.8
17.3
Sore throat
15.8
17.4
20.3
Irritability
8.6
5.6
7.2
Headache
11.0
22.2
26.8
Chillls
5.5
7.2
10.0
Vomiting
5.7
4.1
1.6
Muscle aches
8.4
9.0
16.8
Fatigue
12.4
15.0
18.6

Adverse Events

Time Frame 3, 21, 42 days, and 6 months post vaccination
Adverse Event Reporting Description This study assessed for medically attended events (MAEs) not adverse events. 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. Results for MAEs are reported in the Outcome Measures.
Arm/Group Title FluMist Recipients
Arm/Group Description
All Cause Mortality
FluMist Recipients
Affected / at Risk (%) # Events
Total / (NaN)
Serious Adverse Events
FluMist Recipients
Affected / at Risk (%) # Events
Total 202/63061 (0.3%)
Blood and lymphatic system disorders
Anaemia 2/63061 (0%) 2
Lymphadenitis 1/63061 (0%) 1
Cardiac disorders
Angina unstable 1/63061 (0%) 1
Atrial fibrillation 1/63061 (0%) 1
Cardiac failure congestive 1/63061 (0%) 1
Coronary artery disease 1/63061 (0%) 1
Congenital, familial and genetic disorders
Cleft palate 1/63061 (0%) 1
Congenital anomaly 3/63061 (0%) 3
Eye anterior chamber congenital anomaly 1/63061 (0%) 1
Factor ix deficiency 1/63061 (0%) 1
Pierre robin syndrome 1/63061 (0%) 1
Ear and labyrinth disorders
Deafness 2/63061 (0%) 2
Endocrine disorders
Goitre 1/63061 (0%) 1
Eye disorders
Retinal detachment 1/63061 (0%) 1
Gastrointestinal disorders
Abdominal pain 5/63061 (0%) 5
Colitis ulcerative 2/63061 (0%) 2
Constipation 1/63061 (0%) 1
Dyspepsia 1/63061 (0%) 1
Gastric ulcer 1/63061 (0%) 1
Gastrooesophageal reflux disease 2/63061 (0%) 2
Malocclusion 1/63061 (0%) 1
Pancreatitis 4/63061 (0%) 4
Peritoneal adhesions 1/63061 (0%) 1
Tooth disorder 2/63061 (0%) 2
Umbilical hernia 1/63061 (0%) 1
Vomiting 1/63061 (0%) 1
General disorders
Adverse drug reaction 1/63061 (0%) 1
Chest pain 3/63061 (0%) 3
Hepatobiliary disorders
Cholecystitis 2/63061 (0%) 2
Cholelithiasis 4/63061 (0%) 4
Infections and infestations
Abscess 1/63061 (0%) 1
Appendicitis 9/63061 (0%) 9
Arthritis bacterial 1/63061 (0%) 1
Cellulitis 4/63061 (0%) 4
Diverticulitis 1/63061 (0%) 1
Gastroenteritis 2/63061 (0%) 2
Infectious mononucleosis 1/63061 (0%) 1
Osteomyelitis 2/63061 (0%) 2
Pelvic inflammatory disease 1/63061 (0%) 1
Pneumonia 3/63061 (0%) 3
Psoas abscess 1/63061 (0%) 1
Rash pustular 1/63061 (0%) 1
Sinusitis 1/63061 (0%) 1
Staphylococcal bacteraemia 1/63061 (0%) 1
Tuberculosis 1/63061 (0%) 1
Urinary tract infection 2/63061 (0%) 2
Viral infection 1/63061 (0%) 1
Injury, poisoning and procedural complications
Ankle fracture 1/63061 (0%) 1
Comminuted fracture 1/63061 (0%) 1
Drug exposure during pregnancy 2/63061 (0%) 2
Incisional hernia 1/63061 (0%) 1
Injury 15/63061 (0%) 15
Open wound 1/63061 (0%) 1
Overdose 1/63061 (0%) 1
Poisoning 1/63061 (0%) 1
Road traffic accident 2/63061 (0%) 2
Metabolism and nutrition disorders
Diabetes mellitus 1/63061 (0%) 1
Hyperlipidaemia 1/63061 (0%) 1
Musculoskeletal and connective tissue disorders
Back pain 1/63061 (0%) 1
Kyphosis 1/63061 (0%) 1
Musculoskeletal pain 1/63061 (0%) 1
Scoliosis 2/63061 (0%) 2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign hydatidiform mole 1/63061 (0%) 1
Benign neoplasm 3/63061 (0%) 3
Breast cancer 2/63061 (0%) 2
Colon cancer 2/63061 (0%) 2
Leiomyoma 1/63061 (0%) 1
Leukaemia 1/63061 (0%) 1
Lung neoplasm malignant 1/63061 (0%) 1
Neoplasm malignant 1/63061 (0%) 1
Non-hodgkin's lymphoma 1/63061 (0%) 1
Renal cancer 1/63061 (0%) 1
Uterine leiomyoma 3/63061 (0%) 3
Nervous system disorders
Autism 1/63061 (0%) 1
Cerebrovascular accident 1/63061 (0%) 1
Convulsion 1/63061 (0%) 1
Dystonia 1/63061 (0%) 1
Epilepsy 6/63061 (0%) 6
Febrile convulsion 2/63061 (0%) 2
Headache 1/63061 (0%) 1
Hemicephalalgia 1/63061 (0%) 1
Meningitis eosinophilic 1/63061 (0%) 1
Migraine 1/63061 (0%) 1
Petit mal epilepsy 1/63061 (0%) 1
Syncope 1/63061 (0%) 1
Thoracic outlet syndrome 1/63061 (0%) 1
Viith nerve paralysis 4/63061 (0%) 4
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 8/63061 (0%) 8
Blighted ovum 1/63061 (0%) 1
Ectopic pregnancy 2/63061 (0%) 2
Pregnancy 1/63061 (0%) 1
Psychiatric disorders
Alcohol abuse 1/63061 (0%) 1
Alcohol withdrawal syndrome 1/63061 (0%) 1
Anorexia nervosa 1/63061 (0%) 1
Dependence 1/63061 (0%) 1
Eating disorder 1/63061 (0%) 1
Major depression 1/63061 (0%) 1
Mental disorder 15/63061 (0%) 15
Suicide attempt 1/63061 (0%) 1
Reproductive system and breast disorders
Breast pain 1/63061 (0%) 1
Endometriosis 1/63061 (0%) 1
Menstrual disorder 1/63061 (0%) 1
Uterine prolapse 1/63061 (0%) 1
Respiratory, thoracic and mediastinal disorders
Pleural effusion 1/63061 (0%) 1
Pulmonary oedema 1/63061 (0%) 1
Rhinitis allergic 1/63061 (0%) 1
Skin and subcutaneous tissue disorders
Hyperhidrosis 1/63061 (0%) 1
Surgical and medical procedures
Elective procedure 2/63061 (0%) 2
Female sterilisation 1/63061 (0%) 1
Vascular disorders
Deep vein thrombosis 1/63061 (0%) 1
Kawasaki's disease 1/63061 (0%) 1
Other (Not Including Serious) Adverse Events
FluMist Recipients
Affected / at Risk (%) # Events
Total 0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome. The PIs also agree for data to be presented first as a joint, multi-center publication.

Results Point of Contact

Name/Title Chris Ambrose, MD, Sr Director, Medical Affairs
Organization MedImmune, LLC
Phone 301-398-0000
Email ambrosec@medimmune.com
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00113880
Other Study ID Numbers:
  • FM025
First Posted:
Jun 13, 2005
Last Update Posted:
Jan 8, 2013
Last Verified:
Dec 1, 2012