Data and Approaches in National and International Immunization Studies. Emory University, Schools of Public Health & Medicine & CHRSE

Transcription

1 Data and Approaches in National and International Immunization Studies Saad B. Omer, MBBS MPH PhD Emory University, Schools of Public Health & Medicine & CHRSE

2 Outline Characteristics of vaccine refusers Potential methodological issues relevant to studies among refusers Potential for conducting international studies Limitations of international data

3 Can We Conduct Vaccine Outcome Studies in Vaccine Refusers?

4 School Immunization Requirements State laws (not federal) Major role in low rates of vaccine preventable diseases Exemptions Medical (50 states) Religious (48 states) Personal belief (philosophical) exemptions (20 states) A model to study vaccine refusal

5 Nonmedical Exemptions for States With Religious Exemptions and With Personal Belief Exemptions Only Religious Exemptions Permitted Personal Belief Exemptions Permitted Exemption Ra ate Omer et al., JAMA, 2006 Data updated

6 WA State Counties School Entry Exemption Rates Omer et al., New Eng Journal of Medicine, 2009

7 Relative Locations of Pertussis Space-time Clusters & Exemptions Spatial Clusters Overlap of Exemptions Clusters with Pertussis Clusters Unadjusted OR 3.0 ( ) Adjusted OR 2.7 ( ) Omer, Enger, Moulton et al., Am. J. Epi., 2008

8 Parents Perceptions by Child's Vaccination Status p<0.01 p<0.01 p<0.01 p<0.01 p<0.01 p<0.01 Salmon, Moulton, Omer et al., AJPH, 2005

9 Provider Perceptions of Exempt vs. Vaccinated Children Disease Susceptibility Disease Severity Vaccine Efficacy Health Care Provides in High Category Association with Parent Responses Exempt Vaccinated Odds Ratio Vaccine Safety * * P Value <0.05 Salmon, Pan, Omer et al., Human Vacc. 2009

10 Care Seeking Behavior Parents of exempt children more likely to report use CAM professionals by immediate family members 79.6% (exempt) vs 51.2% (vaccinated) Salmon, Moulton, Omer et al. Arch Ped Adol Med, 2005

11 Number of recommended vaccines received for children with nonmedical exemptions n = % Salmon, Moulton, Omer et al. Arch Ped Adol Med, 2005

12 Recommended vaccines not received by children with nonmedical exemptions n = 277 Salmon, Moulton, Omer et al. Arch Ped Adol Med, 2005

13 Characteristics of Unvaccinated ( Zero Dose ) vs. Under-vaccinated Children Unvaccinated children more likely to be: Male White Belong to households with higher income Married mother with a college education Live with 4 children Smith, Chu, & Baker, Pediatrics, 2004

14 Methodological Issues With Assessing Outcomes in Vaccine Refusers Only a quarter of exempt children refuse all vaccines Risk profile different from the general population External validity Selection bias Information & selection bias due to differential health seeking behavior

15 Developing Evidence-base from International Studies Delays in New Vaccine Introduction in Low Income Countries

16 Hib Vaccine Introduction in High & Low-income Countries GAVI Alliance 2012

17 Hepatitis B Vaccine Introduction in High & Lowincome Countries GAVI Alliance 2012

18 Developing Evidence-base from International Studies Case Study of Maternal Influenza Immunization

19 Odds Ratios of Cardiopulmonary Events by Pregnancy Status Tennessee Medicaid Program Odds Ratio os Data Source: Neuzil et al, AJE, 1998

20 Influenza-Associated Mortality Rate Among Children in the United States, Mortality Rate per 100 0,000 Person-Years Influenza vaccine not available < 6 mos 6-11 mos 1 year 2 years 3 years 4 years 5-10 years Age Group Bhat N, NEJM; years Bhat N, NEJM; 2005.

21

22 Mothers Gift Randomized, Double-blind, Controlled Trial Dhaka, Bangladesh Aug 04 December 05

23 Laboratory-Proven Influenza in Infants Whose Mothers Received Influenza Vaccine vs Controls 63% Efficacy Zaman et al., New Eng Journal of Medicine, 2008

24 Difference in Birth Weight by Maternal Influenza Immunization & Influenza Activity Period Steinhoff, Omer, Roy et al., IDSA, 2009

25 Cohort analysis of surveillance data Birth outcomes & influenza vaccine data: Georgia Pregnancy Risk Assessment Monitoring System Influenza activity data State and Territorial Epidemiologists Reports Based on lab-based and syndromic data Omer et al., PLoS Medicine, 2011

26 Adjusted Odds Ratios of Prematurity by Maternal Influenza Vaccine Status Analysis Period Odds Ratio (95% CI) P value All seasons/periods 0.82 ( ) 0.28 Putative flu season (Oct-May) 0.60 ( ) 0.02 Period of widespread activity 0.28 ( ) 0.01 Omer et al., PLoS Medicine, 2011

27 Adjusted Odds Ratios of Small for Gestational Age by Maternal Influenza Vaccine Status Analysis Period Odds Ratio (95% CI) P value All seasons/periods 0.83 ( ) 0.29 Putative flu season (Oct-May) 0.74 ( ) 0.18 Period of widespread activity 0.31 ( ) Omer et al., PLoS Medicine, 2011

28 Limitations of International Studies I Generalizability to the U.S. Better for GCP compliant trials Ethically, only interventions with Ethically, only interventions with relevance to the country where the study is being conducted can be evaluated

29 Limitations of International Studies II Randomized trials can only be done prior to the widespread introduction of vaccines Only appropriate for evaluating specific vaccines not the whole schedule

30 Thank You!