FinOM Efficacy Trial of 7Valent Pneumococcal Conjugate Vaccine

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FinOM Efficacy Trial of 7-Valent Pneumococcal
Conjugate Vaccine

• Terhi Kilpi
• National Public Health Institute (KTL)
• Finland

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FinOM Study Group
FinOM Vaccine Trial

• Principal investigator
• Study coordination
• Bacteriology
• Immunology
• Otorhinolaryngology
• Biostatistics
• Data management
• Virology
• Study clinic personnel
• Senior adviser

• Juhani Eskola, Terhi Kilpi
• Arto Palmu , Kari S Lankinen
• Elja Herva, Maija Leinonen
• Helena Käyhty, Heidi Åhman
• Pekka Karma
• Jukka Jokinen, Mika Lahdenkari, Jouko Verho
• Jaason Haapakoski, Esa Ruokokoski, Marko Grönholm
• Tapani Hovi
• Wilhelm Bredenberg, Heljä Savolainen, Ritva
  Syrjänen
• P Helena Mäkelä

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FinOM Vaccine Trial

• evaluated efficacy of two 7-valent pneumococcal
  (Pnc) conjugate vaccines for prevention of AOM
  due to vaccine serotypes in children less than 2
  years of age
• clinical phase from December 1995 to March 1999
• 2 497 children enrolled (55 of the birth
  cohort) in Tampere area

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Study design
FinOM Vaccine Trial

• All children were randomized to receive PncCRM
  (Prevnar, Prevenar), PncOMPC, or control (HBV)
  vaccine at 2, 4, 6, and 12 mo
• Follow-up from 2 to 24 mo at the study clinic
• All respiratory infections requiring medical
  attention were evaluated and treated at the study
  clinic

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Definition of AOM
FinOM Studies

• Symptoms
• At least one of the following fever, earache,
  irritability, diarrhea, vomiting, acute otorrhea
  not caused by otitis externa, or other symptoms
  of respiratory infection
• Signs
• A visually abnormal tympanic membrane (in regard
  of color, position and/or mobility) suggesting
  middle ear effusion

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Acute Otitis Media (AOM)
FinOM Studies

• Myringotomy with aspiration performed in AOM with
  effusion
• Middle ear fluid (MEF) sample for bacterial
  culture, pneumococcal serotyping and pneumolysin
  PCR
• AOM episode defined to start at diagnosis and to
  last for 30 days

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Efficacy of PncCRM against AOM
FinOM Vaccine Trial

• Primary
• All AOM episodes due to vaccine serotypes
• Secondary
• First and subsequent AOM episodes due to vaccine
  serotypes
• Other
• All Pnc AOM episodes
• All AOM episodes
• Recurrent AOM

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Efficacy of PncCRM against AOM
FinOM Vaccine Trial

• Post Hoc
• AOM episodes due to vaccine related serotypes
  (6A, 9N, 18B, 19A, 23A)
• AOM episodes due to serotypes unrelated to
  vaccine types
• AOM episodes due to individual serotypes

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Disposition of subjects
FinOM Vaccine Trial
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All AOM episodes due to vaccine serotypes
Primary analysis
FinOM Vaccine Trial
Per protocol follow-up from 6.5 to 24 months of
age
Vaccine efficacy 57 (95 CI 44 to 67)
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First and subsequent AOM episodes due to vaccine
serotypes
Secondary analysis
FinOM Vaccine Trial
Per protocol follow-up
Per person-year
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Summary of efficacy results
FinOM Vaccine Trial
Acute Otitis Media
Per protocol follow-up from 6.5 to 24 months of
age
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Summary of efficacy results
FinOM Vaccine Trial
Acute Otitis Media
Intention to treat follow-up from 2 to 24 months
of age
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Pneumococcal AOM episodes
FinOM Vaccine Trial
Acute Otitis Media
Per protocol follow-up from 6.5 to 24 months of
age
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PCR counts in MEF of Pnc Ply PCR positive AOM
FinOM Vaccine Trial
GM (95 CI)
PCR counts
Pnc culture positive
Pnc culture negative
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Individual vaccine serotypes
FinOM Vaccine Trial
Acute Otitis Media
Per protocol follow-up
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Vaccine, vaccine-related and other serotypes
FinOM Vaccine Trial
Acute Otitis Media
Per protocol follow-up
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Vaccine-related serotypes
FinOM Vaccine Trial
Acute Otitis Media
Per protocol follow-up
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PncCRM
FinOM Vaccine Trial
Conclusions

• is efficacious against
• culture-confirmed, vaccine serotype specific AOM
  (VE 57)
• culture-confirmed AOM due to vaccine-related
  serotypes (VE 51)
• culture-confirmed pneumococcal AOM (VE 34)

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Extended follow-up
FinOM Vaccine Trial
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Objectives
FinOM Follow-up Study

• To assess long-term effects of PncCRM on
• pneumococcal carriage
• antibody persistence
• surgery due to OM in the routine practice after
  the Vaccine Trial

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Methods
FinOM Follow-up Study

• Single follow-up visit at the age of 4 to 5 years
  in spring 2001
• Collection of data
• Parental interview
• Pneumatic otoscopy
• Medical records
• Nasopharyngeal, blood and saliva samples

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Inclusion criteria
FinOM Follow-up Study
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Study flow
FinOM Vaccine Trial and Follow-up Study
Children, N
Hospital tympanostomy data available
Eligible children Analysis population 2
Fully evaluated children Analysis population 1
Age, months
Start of long-term follow-up
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Case ascertainment for tube placement
FinOM Follow-up Study

• Fully evaluated children (Analysis population 1)
• Parental interview
• Hospital records from Tampere University
  Hospital, three district hospitals (78)
• Medical records from private physician offices
  for verification (22)
• Eligible children (Analysis population 2)
• Hospital records from Tampere University
  Hospital, three district hospitals

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Tube placement during the Vaccine Trial
FinOM Studies

• Included in the study services
• Close follow-up in the study clinics, active
  treatment strategy, specific criteria for
  referral in the SOP
• Tampere University Hospital
• Free of charge
• Within 4 to 8 weeks of referral

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Tube placement after the Vaccine Trial
FinOM Studies

• Public hospitals
• Nominal charge
• Waiting time 3 to 4 months
• 78
• Private medical centers and hospitals
• Charge 10 x public sector charge
• No waiting time
• 22

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Incidence of tube placement
/ 100 person-years


Age, years
National hospital discharge register and
national sick insurance reimbursement database
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Study flow
FinOM Vaccine Trial and Follow-up Study
Children, N
Eligible children Analysis population 2
Fully evaluated children Analysis population 1
Age, months
Start of long-term follow-up
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Tympanostomy tube placement in fully evaluated
children
FinOM Vaccine Trial and Follow-up Study
Intention to treat follow-up
Per 100 person-years
Analysis population 1
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Tympanostomy tube placement in all eligible
children
FinOM Vaccine Trial and Follow-up Study
Intention to treat follow-up
Per 100 person-years
Analysis population 2
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Cumulative hazard of tympanostomy tube placement
FinOM Vaccine Trial and Follow-up Study
Cumulative hazard
HBV
PncCRM
Fully evaluated children
Start of long-term follow-up
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Cumulative hazard of tympanostomy tube placement
FinOM Vaccine Trial and Follow-up Study
Cumulative hazard
HBV
PncCRM
All eligible children
Start of long-term follow-up
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Kinetics of anti-23F
FinOM Vaccine Trial and Follow-up Study
?g/ml
PncCRM
HBV
Start of long-term follow-up
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Kinetics of anti-19F
FinOM Vaccine Trial and Follow-up Study
?g/ml
PncCRM
HBV
Start of long-term follow-up
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Kinetics of anti-6B
FinOM Vaccine Trial and Follow-up Study
?g/ml
PncCRM
HBV
Start of long-term follow-up
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Long-term effect on otitis media and carriage
FinOM Follow-up Study
P0.05
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PncCRM
FinOM Follow-up Study
Conclusions

• PncCRM reduces tube placement due to OM
• Vaccine efficacy against OM persists for several
  years

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Thank you