Evaluating Adverse Events after Vaccination in the Medicare Population

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Evaluating Adverse Events after Vaccination in
the Medicare Population

• Robert Ball, MD, MPH, ScM
• Chief, Vaccine Safety Branch
• Division of Epidemiology
• CBER, FDA
• FDA/Industry Statistics Workshop
• September 29, 2006

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Collaborators

• CMS
• Lawrence La Voie, Peter Houck, Rebecca Hudson
• FDA/CBER
• Dale Burwen, Miles Braun

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Medicare and Vaccine Safety Background

• Post-licensure observational studies using large
  linked databases can provide important data about
  whether adverse events are associated with
  vaccines.
• Serious adverse events requiring hospitalization
  after vaccination are uncommon, but are important
  to evaluate to ensure safe vaccination and
  maintain the publics confidence in vaccination.
• Medicare data can help fill an important need
  because other databases may not have sufficient
  statistical power to examine rare events, and may
  under represent the elderly.

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Medicare and Vaccine Safety Background

• 41 million Medicare beneficiaries (96 of 65
  year olds in US).
• 35 million 65 years old.
• 6 million are younger with disabilities or end
  stage renal disease.
• Key consumers of influenza and pneumococcal
  vaccines.
• Nearly all of the elderly, and many younger
  beneficiaries, are recommended to receive the
  vaccines based on their high disease risk.
• According to the CDC, routine revaccination of
  immunocompetent persons previously vaccinated
  with pneumococcal vaccine is not recommended,
  although revaccination once is recommended for
  certain persons provided that 5 years have
  elapsed since receipt of the first dose, and
  revaccination following a second dose is not
  routinely recommended.
• Pneumococcal and influenza vaccination have been
  covered benefits in the Medicare program since
  1981 and 1993, respectively.

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Medicare and Vaccine Safety Study Questions

• Can Medicare data be used to evaluate adverse
  events after influenza and pneumococcal vaccines?
• Is hospitalization for urinary tract infection
  (UTI), not likely associated with vaccination, or
  for cellulitis and abscess of the upper arm and
  forearm (CAUAF) associated with vaccination?
• What are the data quality issues relevant to
  vaccine safety analyses?

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Methods Description of Study and Statistical
Analysis

• Case series design to evaluate the frequency of
  hospitalization during the period immediately
  after vaccination compared with the average
  frequency during the periods before and after
  vaccination.
• Only persons who both were vaccinated and were
  hospitalized for the selected condition were
  included.
• 7 days immediately preceding vaccination were
  excluded because of the healthy vaccinee effect
  vaccinated persons are less likely to be acutely
  ill and hospitalized.
• Determined the average frequency based on 54 days
  (days 8 to 30 prior to vaccination and days 0 to
  30 after vaccination).
• Tested whether the frequency of hospitalization
  deviated from a uniform distribution equal to the
  average frequency using the ?2 goodness-of-fit
  test.
• If the observed frequency during the 54 days
  deviated from the uniform distribution, we tested
  whether the deviation localized to the week after
  vaccination by omitting days 0 to 7, and
  repeating the ?2 goodness-of-fit test for
  deviation from a uniform distribution.
• Among the cohort of persons who received
  pneumococcal vaccine in 2001, we evaluated
  whether prior receipt of vaccine and shorter
  interval between vaccinations (lt5 years) were
  risk factors for hospitalization for cellulitis
  and abscess of the upper arm and forearm (CAUAF).
  
• Proportions were compared using ?2.

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Methods Data Quality Assessment

• To assess agreement with other data sources, we
  compared vaccine coverage rates using Medicare
  claims data to published rates obtained from
  survey data including
• Agency for Healthcare Research and Qualitys
  (AHRQ) Consumer Assessment of Health Plan
  Surveys (CAHPS)
• CMS Medicare Current Beneficiary Survey (MCBS)
• Centers for Disease Control and Preventions
  (CDC) National Health Information Survey (NHIS)
• State-based Behavioral Risk Factor Surveillance
  System (BRFSS)

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Methods Data Sources

• Data from the National Claims History File and
  Enrollment Database for 2001
• 2001 Medicare 5 sample and the 1991-2001
  Pneumococcal Vaccine File

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Interval Between Influenza Immunization and
Admission Date for Selected Conditions
Number of Hospitalizations
Days before vaccination Days
after vaccination
Date of vaccination
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Interval Between Pneumococcal Immunization and
Admission Date for Selected Conditions
Number of Hospitalizations
Days before vaccination Days
after vaccination
Date of vaccination

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Interval Between Receipt of Last Two Pneumococcal
Vaccines, Among Persons Vaccinated in 2001
Number of Persons
Years
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Influenza Vaccination Rates (per 100), Persons
Age 65, by Data Source
TABLE 1. Influenza Vaccination Rates (per 100),
Persons Age 65, by Data Source  

  Abbreviations CAHPS, Consumer Assessment of
Health Plan Surveys MCBS, Medicare Current
Beneficiary Survey NHIS, National Health
Interview Survey BRFSS, Behavioral Risk Factor
Surveillance System NA, published results not
available.
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Pneumococcal Vaccination Rates (per 100), Persons
Age 65, by Data Source
TABLE 2. Pneumococcal Vaccination Rates (per
100), Persons Age 65, by Data Source  
TABLE 1. Influenza Vaccination Rates (per 100),
Persons Age 65, by Data Source  


Abbreviations CAHPS, Consumer Assessment of
Health Plan Surveys MCBS, Medicare Current
Beneficiary Survey NHIS, National Health
Interview Survey BRFSS, Behavioral Risk Factor
Surveillance System NA, published results not
available.
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Conclusions

• Using Medicare administrative data, we identified
  a possible increased risk of hospitalization for
  cellulitis and abscess of the upper arm and
  forearm after pneumococcal vaccine, but not
  influenza vaccine.
• This risk of hospitalization was not detected in
  smaller studies.
• Injection site reactions are likely to often be
  misdiagnosed as cellulitis. These data are
  consistent with the known local reactogenicity of
  pneumococcal vaccine.
• The revaccination rate for pneumococcal vaccine
  is higher than expected and the interval of
  revaccination in some cases is shorter than
  expected (lt5 years) based on current
  recommendations.

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Conclusions

• A potential limitation of Medicare data
  identified is the difference in vaccination rates
  between claims data and survey data.
• This limitation can be addressed using the case
  series study design, where only individuals who
  have both the condition under study and received
  the vaccine are included.
• Screening analyses can be performed using
  administrative data, but medical record review to
  validate diagnoses will often be needed for
  rigorous study of vaccine-adverse event
  associations.
• Current and future projects include the
  evaluation of Guillain Barre Syndrome after
  influenza vaccine, cellulitis after pneumococcal
  polysaccharide vaccine, and pandemic influenza
  vaccine safety preparedness.

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Distribution of vaccine claim dates, Medicare
data, 5 sample, 2001
Percent
Month