Observational Surveillance Study to Detect Potential Safety Signals in Patients Who Have Had at Least One Dose of GARDASIL™ (V501-031)

A Post-licensure Surveillance Program for the Safety of GARDASIL™ in a Managed Care Organization Setting

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™.

Study Overview

• Status: Completed
• Conditions: Human Papillomavirus Infection

• Study Type: Observational
• Enrollment (Actual): 189629

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

Managed Care Organizations (MCO) databases

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort
3-Dose Safety Population (Primary); Females between ages 9 to 26 at receipt of the first dose of GARDASIL who are members of the participating MCOs and have completed the 3-dose regimen of GARDSIL vaccination with 12 months.
Pregnancy Safety Population; Females who received at least one dose of GARDASIL during pregnancy.
Autoimmune Safety Population; Females who have received at least one dose of GARDASIL and have been members in the same MCO for at least 12 months prior to receiving their first dose of GARDASIL.
Any Dose Safety Population (Secondary); Females who have received at least one dose of GARDASIL and have been members in the same MCO for at least 12 months prior to receiving their first dose of GARDASIL.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	On day of each vaccination
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.	Within 14 days and within 60 days immediately after each vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	First dose of Gardasil in pregnancy up to 6 months after birth
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.	First dose of Gardasil in pregnancy up to pregnancy resolution
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.	within 6 months immediately after each vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Kaiser Permanente

Publications and helpful links

General Publications

• Chao C, Klein NP, Velicer CM, Sy LS, Slezak JM, Takhar H, Ackerson B, Cheetham TC, Hansen J, Deosaransingh K, Emery M, Liaw KL, Jacobsen SJ. Surveillance of autoimmune conditions following routine use of quadrivalent human papillomavirus vaccine. J Intern Med. 2012 Feb;271(2):193-203. doi: 10.1111/j.1365-2796.2011.02467.x. Epub 2011 Nov 15.
• Klein NP, Hansen J, Chao C, Velicer C, Emery M, Slezak J, Lewis N, Deosaransingh K, Sy L, Ackerson B, Cheetham TC, Liaw KL, Takhar H, Jacobsen SJ. Safety of quadrivalent human papillomavirus vaccine administered routinely to females. Arch Pediatr Adolesc Med. 2012 Dec;166(12):1140-8. doi: 10.1001/archpediatrics.2012.1451.

Helpful Links

• EUPAS Register (EUPAS17730)

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2007
• Primary Completion (Actual): December 13, 2010
• Study Completion (Actual): December 13, 2010

Study Registration Dates

• First Submitted: February 26, 2010
• First Submitted That Met QC Criteria: March 1, 2010
• First Posted (Estimate): March 2, 2010

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Human Papillomavirus (HPV)
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Tumor Virus Infections; Papillomavirus Infections
• Other Study ID Numbers: V501-031; 2010_019; EP08014.031 (Other Identifier: Merck)