Quadrivalent Human Papillomavirus Vaccine (HPV4) Adverse Events Vaccine Adverse Event Reporting System (VAERS) John Iskander MD MPH Immunization Safety Office

Safety Data for HPV4: Learning Objective Participants will be able to describe adverse events (AEs) most commonly reported to the Vaccine Adverse Event Reporting System (VAERS) following quadrivalent human papillomavirus (HPV4) (types 6,11,16,18) recombinant vaccine.

Safety Data for HPV4: Outline VAERS background Overview of all HPV4 Adverse Event Reports HPV4 Adverse Event Reports among females aged 9-26 years HPV4 safety data compared to other adolescent vaccinations among females aged 9-26 year

VAERS Overview A national vaccine safety surveillance program co-managed by CDC and FDA collects and analyzes information from reports of possible adverse events following immunization helps to ensure that the benefits of immunizations continue to be far greater than the risks National in scope covering a diverse population Useful for generating signals for new, unusual, or rare events

Safety Data for HPV4: Adverse Events Reported to VAERS 852 total reports received as of February 27, 2007 > 3.2 million doses distributed through January 2007 Demographics 96% (n=816) females 36% (n=310) persons aged 18-29 years 33% (n=280) persons aged 6-17 years 28% (n=236) age unknown

Safety Data for HPV4: Adverse Events Reported to VAERS Onset interval 39% (n=334) day of vaccination (day 0) 11% (n=97) day 1 34% (n=289) unknown interval Range 0 to over 120 days; median <1 day Recovery 46% (n=388) recovered 30% (n=258) unknown recovery status Source of reports 77% (n=652) vaccine manufacturer 9% (n=76) provider

Safety Data for HPV4: Most frequently reported terms MedDRA Term n % based on N = 852 Dizziness 96 11 Syncope 92 Injection Site Pain 88 10 Pain 73 9 Nausea 72 More than one code may be assigned to a single event.

Safety Data for HPV4: Co-administered Vaccines % Based on N=852 HPV4 alone 752 88 HPV4 and MNQ 16 2 Hep A and HPV4 11 1 Flu and HPV4 10 HPV4 and Tdap 8

Safety Data for HPV4: Serious Reports* 88% (36/41) HPV4 alone No deaths 37% (15/41) required hospitalization Recovery 39% (16/41) recovered 37% (15/41) patient had not recovered * Defined by Code of Federal Regulations as involving hospitalization, death, disability, life threatening illness, or certain other medically important conditions

Safety Data for HPV4: Most frequently reported serious terms MedDRA Term n % Based on N=41 Computerized Tomogram Normal 7 17 Vomiting 6 15 Nausea Dehydration 5 12 Pyrexia Dizziness More than one code may be assigned to a single event.

Safety Data for HPV4: Guillain Barré Syndrome 3 reports of GBS after HPV4 13 y/o onset 8 days; received PPV within 30 days of HPV4; unknown recovery status 16 y/o onset unknown; received HPV4 alone; not recovered at time report submitted 13 y/o onset 13 days; received MNQ and HPV4 at the same time; unknown recovery status

Safety Data for HPV4: Adverse Events Reported to VAERS Females ages 9-26 567 total reports as of Feb 27, 2007 Onset interval 46% (n=259) day of vaccination (day 0) 14% (n=81) day 1 19% (n=108) unknown onset interval Range: 0 to over 120 days; median 0 days (day of vaccination)

Safety Data for HPV4: Most frequently reported terms Females ages 9-26 As coded using the MedDRA preferred terms. More than one code may be assigned to a single event MedDRA Term n % Based on N=567 Dizziness 70 12 Nausea 55 10 Injection Site Pain 53 9 Pain 52 Syncope 49

Safety Data for HPV4: Serious Events* Females ages 9-26 6% (41/567) serious reports 86% (36/41) HPV4 alone 36% (36/41) required hospitalization Recovery 44% (16/41) recovered 39% (14/41) not recovered * Defined by Code of Federal Regulations as involving hospitalization, death, disability, life threatening illness, or certain other medically important conditions

Safety Data for HPV4: Most frequently reported serious terms Females ages 9-26 MedDRA Term n % Based on N=36 Computerized Tomogram Normal 7 19 Vomiting 6 17 Dehydration 5 14 Pyrexia Nausea More than one code may be assigned to a single event.

Safety Data for HPV4: Syncope Females ages 9-26 55 reports 82% (n=45) HPV4 alone 6% (n=3) serious Onset 66% (n=36) day of vaccination (day 0) 29% (n=16) day 1 Recovery 58% (n=32) recovered 29% (n=16) unknown recovery

Safety Data for HPV4: Syncope and other Adolescent Vaccines Females ages 9-26 Hepatitis B (N=5298) 297 reports 51% (n=151) Hep B alone 7% (n=21) serious Menactra (MCV4) (N=570) 30 reports 43% (n=13) MCV4 alone No serious reports Tdap (N=396) 24 reports 33% (n=8) Tdap alone

Safety Data for HPV4: Common Adverse Event Comparison Females ages 9-26 HPV4 (N=567) % Menactra (N=570) Tdap (N=396) Hep B (N=5298) Dizziness 12 13 11 Injection Site Pain 9 8 Pain 17 15 Syncope 5 6

Limitations of VAERS Limitations Underreporting (differential reporting) Preferential reporting of events proximal to immunization Inaccurate, or incomplete information Stimulated reporting No basis for calculating incidence rates of adverse events

Conclusion Overall HPV4 has a favorable safety profile; there have been few serious reports The proportion of syncope reports is slightly higher in females ages 9-26 who received HPV4 compared to other vaccines Providers should follow ACIP recommendations for prevention of accidents due to syncope following vaccination: Providers should *strongly consider observing patients for 15 minutes after they are vaccinated. If syncope develops, patients should be observed until the symptoms resolve. Centers for Disease Control and Prevention. General Recommendations on Immunization: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep 2006; 55; 1-48. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5515a1.htm

Background Slides

Safety Data for HPV4: Adverse Events Reported to VAERS Females ages 9-26 Recovery 48% (n=270) reported recovered at time report submitted 25% (n=140) unknown 24% (n=137) reported not recovered at time report submitted Source of reports 69% (n=390) vaccine manufacturer 12% (n=66) provider

Safety Data for HPV4: Co-administered Vaccines Females ages 9-26 % Based on N=567 HPV4 alone 484 85 HPV4 and MNQ 16 3 Hep A and HPV4 11 2 Flu and HPV4 10 HPV4 and Tdap 7 1

Safety Data for HPV4: Injection Site Pain Females ages 9-26 50 reports 86% (n=43) HPV4 alone 2% (n=1) serious Onset interval 52% (n=26) day of vaccination (day 0) 10% (n=5) day 1 Recovery 42% (n=21) recovered 34% (n=17) unknown recovery

Injection Site Pain and other Adolescent Vaccines Females ages 9-26 Hepatitis B 408 reports 63% (n=258) Hep B alone 3% (n=11) serious Menactra 44 reports 59% (n=26) MCV4 alone 2% (n=1) serious Tdap 46 reports 67% (n=31) Tdap alone

Safety Data for HPV4 Common Adverse Event Comparison Females ages 9-26 HPV4 (N=567) n % Menactra (N=570) Tdap (N=396) n % Hep B (N=5298) n % Dizziness 70 12 71 13 49 569 11 Injection site pain 53 9 44 8 46 412 Pain 52 99 17 59 15 463 Syncope 30 5 20 289 6