Immunization Safety Office: Overview and Considerations on Safety of Alternative Immunization Schedules

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1 Immunization Safety Office: Overview and Considerations on Safety of Alternative Immunization Schedules Frank DeStefano MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion, National Center for Emerging and Zoonotic Infectious Diseases Centers for Disease Control and Prevention (CDC) 1

2 Outline Overview of Immunization Safety Office Vaccine Safety Datalink (VSD) VSD studies of children on different vaccination schedules Examples Feasibility study of under-vaccinated children

3 ISO mission To assess the safety of vaccines administered to children, adolescents and adults Comprehensive approach to vaccine safety includes Surveillance to detect possible adverse events following immunization (AEFI) in a timely way Investigation and research of possible AEFI to determine causality and risk factors Development of strategies for prevention of AEFI Timely communication and education to partners and public

4 ISO: Monitoring systems and research activities Vaccine Adverse Event Reporting System (VAERS) Clinical Immunization Safety Assessment Network (CISA) Vaccine Safety Datalink (VSD) 4

5 Vaccine Adverse Event Reporting System (VAERS) A national vaccine safety surveillance system that receives voluntary reports of adverse events following immunization Mandated by the 1986 Childhood Vaccine Injury Act Mission to provide comprehensive post-marketing safety surveillance of vaccines licensed in the U.S. Co-sponsored by CDC and FDA Helps to rapidly detect potential vaccine safety concerns ( signals ) 5

6 CISA CDC established the Clinical Immunization Safety Assessment Network (CISA) in 2001 to Conduct individual-level clinical vaccine safety research Investigate pathophysiologic mechanisms and biologic basis of adverse events following immunization (AEFI) Provide evidence-based recommendations for the evaluation, diagnosis and management of AEFIs CISA network sites: Boston Medical Center Johns Hopkins Univ Stanford Univ Columbia Univ Med Center No. California Kaiser Permanente Vanderbilt Univ Medical Center 6

7 Studies of the Immunization Schedule: VAERS and CISA VAERS and CISA Assess individual cases Usually one vaccine adverse event pair Not suitable for studying simultaneous or cumulative immunizations over time

8 Vaccine Safety Datalink (VSD) Established in 1990 A collaborative project among CDC and 10 managed care organizations (MCOs) Allows for planned epidemiologic studies of Allows for planned epidemiologic studies of vaccine safety as well as timely investigation of new vaccine safety signals

9 Group Health Cooperative Northwest Kaiser Permanente No. CA Kaiser Permanente So. CA Kaiser Permanente VSD Sites: 2011 Health Partners Kaiser Permanente Colorado Marshfield Clinic AHIP Kaiser Permanente Georgia Harvard Pilgrim Kaiser Permanente Hawaii

10 Advantages of VSD MCOs for Vaccine Safety Research Identifiable large population (known denominator) Incidence rates and attributable risks Longitudinal follow-up of individuals Computerized data bases (including immunization tracking systems) Studies can be more efficient Ability to review medical charts Integrated systems All levels of care covered (outpatient to hospital) May have pharmacy and laboratory

11 VSD Annual Cycle Files + Chart Review Procedure Codes ER Visits Hospital discharge diagnosis codes Linked by Study IDs Enrollment and demographics Outpatient and Clinic visits + Birth and death certificate information & Family Linkage Immunizations Records

12 The VSD Distributed Data Model CDC Direct SAS Programs, Logs, Output, & Analytical Datasets Hub Indirect

13 Studies of the Immunization Schedule: VSD VSD has a complete longitudinal record of immunizations for individuals who were MCO members from birth VSD MCOs have high vaccination coverage which limits ability to study under-vaccinated individuals Few unvaccinated individuals (limited power) Incompletely vaccinated individuals may be different from fully vaccinated individuals (confounding)

14 VSD Study Methods Acute events following a single vaccine Analyze risk windows (e.g., increased risk of febrile seizure is limited to 5-12 days after a measles-containing vaccine) Self-control methods to address confounding (best for acute events with a defined risk window) Conditions with long latency periods or following multiple vaccinations over time More challenging to study (especially in a highly vaccinated population)

15 VSD Studies of Cumulative Vaccine Examples: Exposures in Early Life Vaccinations and risk of asthma Vaccinations and neurodevelopmental Vaccinations and neurodevelopmental outcomes

16 VSD Study of Infant Vaccinations and Asthma Children enrolled at one of the VSD MCOs Exposure: Vaccinations received in first 18 months of life Outcome: Development of asthma by age 4-7 Total vaccine doses Proportion with asthma Adjusted OR (95% CI) (%) /338 (9) Referent 12 46/494 (9) 1.02 ( ) /946 (8) 1.04 ( ) Maher 2004; Pharmacoepidemiol Drug Saf: 13(1):1-9

17 On-time Vaccinations and Neurodevelopmental Outcomes Children enrolled from VSD MCOs, born Exposure: Vaccinations received in first year of life and categorized according to the highest and lowest exposures during the first 7 months of life Outcome: Neuropsychological functioning as measured by a standardized test battery administered when children were 6-11 years old Results: Of 42 outcomes evaluated, no statistically significant differences favored the less vaccinated children; two favored the most highly vaccinated: Outcome NEPSY speeded naming test Adjusted Coefficient (difference in mean scores) P WISC performance IQ Smith M J, Woods C R Pediatrics 2010;125:

18 Up-to-date status in the study cohort. (3 DTP, 3 Hib, 2 polio, 2 hep B) Smith M J, Woods C R Pediatrics 2010;125: by American Academy of Pediatrics

19 Population-based cohort study of undervaccination and alternative immunization schedules: A VSD feasibility study Objectives 1. Build cohort of undervaccinated children ages 2 to 24 months across 8 MCO sites (N=200,21) 2. Describe patterns and trends of specific alternative immunization schedules over time ( ) 3. Compare health care utilization patterns between undervaccinated children and children on the ACIP schedule

20 Preliminary results 1. Undervaccination increased significantly among children born Prevalence of specific alternative immunization schedules increased significantly among children born Undervaccinated children had significantly lower outpatient utilization rates and significantly higher inpatient utilization rates than children who were age-appropriately vaccinated.

21 Courtesy of Jason Glanz, Kaiser Permanente of Colorado

22 Health care utilization from birth to 36 months (preliminary results) Alternative vaccination schedules (n= 74,986) # visits per 1000 children On-time vaccinations (n= 125,035) # of visits per 1000 children Incidence rate ratios (95% confidence interval) All outpatient (OP) visits 16,083 19, ( ) OP visits for fever ( ) OP visits for pharyngitis ( ) OP visits for sinusitis ( ) OP visits for URI ( ) Well child visits ( ) Inpatient visits ( ) ED visits ( ) ED = emergency department Incidence rate ratios calculated using conditional Poisson regression Courtesy of Jason Glanz, Kaiser Permanente of Colorado

23 Conclusions VSD has complete immunization histories on many members and can identify individuals vaccinated according to alternative vaccination schedules Feasibility of safety studies in VSD of alternative vaccination schedules Must be able to adequately address confounding, including differences in health care utilization More feasible for severe health outcomes that invariably require care through the traditional healthcare system (e.g., type 1 diabetes) Outcomes that do not necessarily require healthcare visits would best be evaluated through in-person assessments (e.g., neurodevelopmental outcomes)