【正文】 i sodes of S am e S erot y pe HBV P ncC RM E stim . 95 % CI P er Analy si s P l an 414 271 34 % 21, 45 E xcl ude sub sequen t epi sode du e to sam e seroty pe 374 245 34 % 21, 44 Finnish OM Study— Supplementary Analysis: Pneumococcal AOM by PCR/Culture Num ber o f E pi sodes V acci ne E ff i cac y Metho d of Diag nosi s Fol l o w up P eri od HBV P ncC RM E stim ate 95 % CI PP 414 271 34 % 21, 45 Cul tur e I TT 467 322 32 % 19, 42 PP 678 541 20 % 7, 31 P CR? I TT 764 635 18 % 5, 29 PP 687 548 20 % 7, 31 Cul tur e or P CR I TT 775 642 18 % 5, 29 ? PCR b ased on pneumo l y si n gen e . Finnish OM Study— Supplementary Analysis*: Antibiotic Use N u mb e r ( % ) o f S u b j e c t s Wh o H a d A n t i b i o t i c s D u r i n g I T T F o l l o w up H B V ( N = 8 3 1 ) P n c C R M ( N = 8 3 1 ) P V a l u e A O M T r e a t men t** 589 ( 7 1 % ) 551 ( 6 6 % ) 0 . 0 5 1 A O M P rev e n t i o n* * 143 ( 1 7 % ) 132 ( 1 6 % ) 0 . 5 0 9 O t h e r P u rpo s e s 147 ( 1 8 % ) 157 ( 1 9 % ) 0 . 5 6 8 R e g a rdl e s s o f P u rpo se 605 ( 7 3 % ) 578 ( 7 0 % ) 0 . 1 5 9 P v a lu e b a se d o n Fi s h e r ’s e x a ct te st . * A n a l y si s r e q u e s t e d b y FD A p o st u n b l i n d i n g . * * A l l e t i o l o g i e s o f A O M . Finnish OM Study Supplementary Analysis: First Tympanostomy Tube Placement HBV P n c C R M N u mb e r o f R a n d o mi ze d S u b j e c t s 831 831 N u mb e r o f S u b j e c t s w i t h E v e n t s 161 153 I n c i d e n c e o f F i rst T u b e P l a c e m e n t 0 . 1 2 0 . 1 1 Finnish OM Followup Study— Tympanostomy Tube Placement ? To assess longterm effect of vaccine on procedures for ear tube placement ? Children evaluated at 45 years of age ? Unblinded ? Two populations evaluated: ? Volunteers in followup study, N= 756 ? Original randomized population, N= 1662 Finnish OM Followup Study— Primary Analysis, Rate of Ear Tube Placement among Children Enrolled in Followup Study V accin e E ff i cac y HBV P ncC RM E stim ate 95 % CI Num ber o f c hi ld ren enrol led 353 403 Rate o f ev ents (/10 0 child y e a rs ) IT T Fol lo w u p 2 m onths 2 y ears 12 % 17, 34 Long term F ol lo w up, 2 y ears 4 to 5 y ears 39 % 4, 61 Finnish OM Followup Study— Secondary Analysis, Rate of Ear Tube Placement among All Children Followed to 45 years of Age V acci ne E ff i cac y HBV P ncC RM E stim ate 95 % CI Num ber o f c hi ld ren enro ll ed 831 831 Rat e? o f ev e nts, I T T F o l l o w u p , 2m o nth s 2y ea rs 4% 19, 23 Num ber o f c hi ld ren av ailabl e for fol lo w up 744 746 Rat e? o f ev e nts, Long term F ol lo w up, 2 y ea rs 4 to 5 y ear 44 % 19, 62 ? Rate as per 1 00 chi l d y e ar s. Northern California Kaiser Permanente (NCKP) Otitis Media Efficacy Results Northern California Kaiser Permanente (NCKP) Study: Elements of Study Design ? Randomized, doubleblind ? Investigational meningococcal C conjugate vaccine control ? AOM a secondary endpoint ? No standardized AOM clinical case definition ? No tympanocentesis or routine culture of MEF ? Automated database searches to identify OM diagnoses NCKP Study: Case Definitions AOM Diagnosis: Based on clinical practice AOM Episode: A clinic visit at which AOM was diagnosed, and at least 21 days had elapsed since any previous visit for AOM Frequent AOM: 3 AOM episodes within 6 months, or 4 episodes within 12 months NCKP Study: Prospectively Defined AOM Endpoints Primary: All AOM episodes Secondary: ? First AOM episode ? Frequent AOM ? First tympanostomy tube ? All OM clinic visits ? Ruptured ear drums NCKP Study: Primary Analysis, Overall Reduction in AOM Episodes N u mb e r o f E p i s o d e s V a c c i n e e f f i c a c y R e d u c t i o n i n A l l A O M E p i s o d e s 7 V P n C M n C C % R e d u c t i o n 9 5 % C I P e r p r o t o c o l 1 6 , 1 2 4 1 7 , 4 0 5 7 . 0 % 4 . 1 , 9 . 7 I n t e n t to t rea t 2 5 , 5 9 0 2 7 , 1 9 9 6 . 4 % 3 . 9 , 8 . 7 E st i m a t e s o f r e l a t i v e r i sk b a se d o n A n d e r s e n G i l l co u n t i n g p r o c e ss o v e r t i m e w i t h t r e a t m e n t a s t h e o n l y co v a r i a t e . NCKP Study: Secondary Analysis, Reduction in Risk of at Least 1 Episode N u mb e r o f C h i l d re n w i t h ? 1 E p i s o d e V a c c i n e e f f i c a c y R e d u c t i o n i n R i s k o f ? 1 A O M E p i s o d e 7 V P n C M n C C % R e d u c t i o n 9 5 % C I P e r p r o t o c o l 7 , 1 2 6 7 , 4 1 1 5 . 4 % 2 . 3 , 8 . 4 I n t e n t to t rea t 1 0 , 1 1 2 1 0 , 3 9 4 4 . 9 % 2 . 3 , 7 . 5 E st i m a t e s o f r e l a t i v e r i s k a n d co n f i d e n ce i n t e r v a l s b a s e d o n C o x r e g r e ssi o n m o d e l o f h a za r d o v e r t i m e , w i t h g e n d e r a s c o v a r i a t e . NCKP Study: Frequent Acute Otitis Media N u m b er o f C h i l d r e n w i t h F r eq u en t A O M V ac ci n e E f f i ca cy F r eq u en t A O M 7V P n C M n C C % R ed u ct i o n 95 % C I P er p r o t o co l 1, 64 7 1, 80 9 9. 5% 3. 2, 15 . 3 I n t en t to t r ea t 2, 61 2 2, 83 9 9. 2% 4. 3, 13 . 9 E st i m a t e s o f r e l a t