Human Papillomavirus Infection
Conditions
Keywords
Human Papillomavirus (HPV)
Brief summary
This is a post-licensure safety surveillance program to detect potential safety signals in subjects, from the managed care organizations database, who have used GARDASIL™.
Interventions
None listed
Sponsors
Kaiser Permanente
Merck Sharp & Dohme LLC
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
9 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
3-Dose Safety Population * Female 9-26 years at the time of first dose of GARDASIL™ * Completed the 3-dose regimen of GARDASIL™ per protocol Pregnancy Safety Population * Received at least one dose of GARDASIL™ up to 30 days prior to the date of conception or any time between conception and the day of pregnancy resolution Autoimmune Safety Population * Female who has received at least one dose of GARDASIL™ * Has been a member of same Managed Care Organization (MCO) for at least 12 months prior to the receipt of GARDASIL™ Any Dose Safety Population * Female who has received at least one dose of GARDASIL™
Exclusion criteria
3-Dose Safety Population * Male * Receives incomplete regimen of GARDASIL™ * Completes the three dose regimen of GARDASIL™ in more than 12 months * Less than 28 day interval between doses 1 and 2 or less than a 12 week interval between doses 2 and 3 * Younger than 9 or older than 26 years of age at receipt of first dose Pregnancy Safety Population * Males * No record of pregnancy at the Managed Care Organization (MCO) Autoimmune Safety Population * Member of the same MCO for less than 12 months prior to receiving the first dose * Male
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Syncope | On day of each vaccination | Syncope was defined as the presence of a syncope diagnosis code in the emergency room or hospital setting in the vaccination risk period or in the post-vaccination self-comparison period. These codes could have represented a new event, a pre-existing event, a prior history of the event, a rule out diagnosis, miscoding, or a misdiagnosis. Consistent with the study's design, diagnosis codes for general safety analyses were not confirmed in this study. |
| Incidence Rate of Cellulitis | Within 14 days and within 60 days immediately after each vaccination | Cellulitis was defined as the presence of a cellulitis or abscess diagnosis code in the emergency room or hospital setting in the vaccination risk period or in the post-vaccination self-comparison period. These codes could have represented a new event, a pre-existing event, a prior history of the event, a rule out diagnosis, miscoding, or a misdiagnosis. Consistent with the study's design, diagnosis codes for general safety analyses were not confirmed in this study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy | First dose of Gardasil in pregnancy up to 6 months after birth | Pregnancy exposure was defined as receipt of Gardasil at any time from 1 month prior to conception through end of pregnancy. |
| Number of Miscarriages Among Females Who Received Gardasil During Pregnancy | First dose of Gardasil in pregnancy up to pregnancy resolution | Pregnancy exposure was defined as receipt of Gardasil at any time from 1 month prior to conception through end of pregnancy. |
| Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil | within 6 months immediately after each vaccination | Autoimmune cases were defined as newly diagnosed cases within 6 months after any dose of Gardasil, as confirmed by medical record review by panels of physicians specializing in the 16 autoimmune conditions of interest. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Any Dose Safety Population Any female who received any dose of Gardasil at a managed care organization (MCO) between August 2006 and March 2008. | 189,629 |
| Total | 189,629 |
Baseline characteristics
| Characteristic | Any Dose Safety Population |
|---|---|
| Age, Customized >26 years | 1679 Participants |
| Age, Customized <9 years | 45 Participants |
| Age, Customized Between 16 and 26 years | 91066 Participants |
| Age, Customized Between 9 and 15 years | 96839 Participants |
| Sex: Female, Male Female | 189629 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Incidence Rate of Cellulitis
Cellulitis was defined as the presence of a cellulitis or abscess diagnosis code in the emergency room or hospital setting in the vaccination risk period or in the post-vaccination self-comparison period. These codes could have represented a new event, a pre-existing event, a prior history of the event, a rule out diagnosis, miscoding, or a misdiagnosis. Consistent with the study's design, diagnosis codes for general safety analyses were not confirmed in this study.
Time frame: Within 14 days and within 60 days immediately after each vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Dose Safety Population | Incidence Rate of Cellulitis | Days 1-14 after vaccination | 3.53 Rate per 1000 person years |
| Any Dose Safety Population | Incidence Rate of Cellulitis | Days 1-60 after vaccination | 2.25 Rate per 1000 person years |
| 3-Dose Safety Population | Incidence Rate of Cellulitis | Days 1-14 after vaccination | 2.17 Rate per 1000 person years |
| 3-Dose Safety Population | Incidence Rate of Cellulitis | Days 1-60 after vaccination | 1.66 Rate per 1000 person years |
Comparison: Days 1-14 after vaccination.95% CI: [1.17, 2.3]unconditional logistic regression
Comparison: Days 1-60 after vaccination.95% CI: [0.82, 1.35]unconditional logistic regression
Comparison: Days 1-14 after vaccination.95% CI: [0.53, 1.98]unconditional logistic regression
Comparison: Days 1-60 after vaccination.95% CI: [0.5, 1.21]unconditional logistic regression
Primary
Incidence Rate of Syncope
Syncope was defined as the presence of a syncope diagnosis code in the emergency room or hospital setting in the vaccination risk period or in the post-vaccination self-comparison period. These codes could have represented a new event, a pre-existing event, a prior history of the event, a rule out diagnosis, miscoding, or a misdiagnosis. Consistent with the study's design, diagnosis codes for general safety analyses were not confirmed in this study.
Time frame: On day of each vaccination
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Any Dose Safety Population | Incidence Rate of Syncope | 24.21 Rate per 1000 person years |
| 3-Dose Safety Population | Incidence Rate of Syncope | 13.84 Rate per 1000 person years |
95% CI: [3.91, 9.21]unconditional logistic regression
95% CI: [1.18, 7.08]unconditional logistic regression
Secondary
Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil
Autoimmune cases were defined as newly diagnosed cases within 6 months after any dose of Gardasil, as confirmed by medical record review by panels of physicians specializing in the 16 autoimmune conditions of interest.
Time frame: within 6 months immediately after each vaccination
Population: Number of females with at least 12 months' membership at a MCO prior to Gardasil.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Dose Safety Population | Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil | No. of potential autoimmune cases | 719 Number of autoimmune cases |
| Any Dose Safety Population | Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil | No. that underwent medical record review | 318 Number of autoimmune cases |
| Any Dose Safety Population | Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil | No. of confirmed new onset cases within 6 months | 124 Number of autoimmune cases |
| Any Dose Safety Population | Number of Cases of New Onset Autoimmune Conditions in Females Receiving at Least One Dose of Gardasil | No. associated with Gardasil by safety committee | 0 Number of autoimmune cases |
Secondary
Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy
Pregnancy exposure was defined as receipt of Gardasil at any time from 1 month prior to conception through end of pregnancy.
Time frame: First dose of Gardasil in pregnancy up to 6 months after birth
Population: Number of females potentially exposed to Gardasil during potential pregnancy as identified from unconfirmed diagnosis codes in electronic medical records.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Dose Safety Population | Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy | Number (No.) of potential congenital anomalies | 170 Number of congenital anomalies |
| Any Dose Safety Population | Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy | No. that underwent medical record review | 170 Number of congenital anomalies |
| Any Dose Safety Population | Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy | No. of confirmed congenital anomalies | 44 Number of congenital anomalies |
| Any Dose Safety Population | Number of Congenital Anomalies Among Females Who Received Gardasil During Pregnancy | No. associated with Gardasil by safety committee | 0 Number of congenital anomalies |
Secondary
Number of Miscarriages Among Females Who Received Gardasil During Pregnancy
Pregnancy exposure was defined as receipt of Gardasil at any time from 1 month prior to conception through end of pregnancy.
Time frame: First dose of Gardasil in pregnancy up to pregnancy resolution
Population: Number of females potentially exposed to Gardasil during potential pregnancy as identified from unconfirmed diagnosis codes in electronic medical records.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Any Dose Safety Population | Number of Miscarriages Among Females Who Received Gardasil During Pregnancy | No. of potential miscarriages indentified | 633 Number of miscarriages |
| Any Dose Safety Population | Number of Miscarriages Among Females Who Received Gardasil During Pregnancy | No. that underwent medical record review | 100 Number of miscarriages |
| Any Dose Safety Population | Number of Miscarriages Among Females Who Received Gardasil During Pregnancy | No. of confirmed miscarriages | 9 Number of miscarriages |
| Any Dose Safety Population | Number of Miscarriages Among Females Who Received Gardasil During Pregnancy | No. associated with Gardasil by safety committee | 0 Number of miscarriages |