【正文】 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: First Tympanostomy Tube Placement N u m b er o f C h i l d r e n w i t h T u b e P l ac e m en t V ac ci n e E f f i ca cy R ed u ct i o n i n F i r s t T y m p an o s t o m y T u b e P l ac eme n t 7V P n C M n C C % R ed u ct i o n 95 % C I P e r p r o t o c o l 157 198 20% 2, 35 I n t en t to t r ea t 192 240 21% 4, 34 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 w e r e 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 z a r d o v e r t i m e . NCKP Study: Ruptured Ear Drums with Pneumococcus Isolated N u mb e r o f R u p t u red E a r D rums V a c c i n e e f f i c a c y R u p t u red E a r D rums 7 V P n C M n C C E s t i mat e 9 5 % C I V a c c i n e S e ro t y p e s P e r P ro t o c o l 4 9 56% 5 9 , 9 0 I n t e n t to t rea t 6 14 57% 1 9 , 8 6 A l l P n e u mo c o c c a l S e rot y p e s P e r P ro t o c o l 5 13 62% 1 5 , 8 9 I n t e n t to tr e a t 7 18 61% 2 4 , 8 6 C o n f i d e n c e l i m i t s b a s e d o n e x a ct b i n o m i a l d i st r i b u t i o n s. NCKP Study: Serotype Distribution of Ruptured Ear Drums with Pneumococcus Isolated (ITT) N u mb e r o f c a s e s d u e t o e a c h s e ro t y p e S e ro t y p e 7 V P n C M n C C 19F 6 7 14 0 4 9V 0 1 23F 0 2 T o t a l o f V a c c i n e S e ro t y p e s 6 14 T o t a l o f A l l P n e u mo c o c c a l S e ro t y p e s 7? 18 ? O n e n o n v a cc i n e s e r o t y p e i s o l a t e d ( 1 9 A ) . NCKP Study: Efficacy Through Extended Followup (ITT) E f f i ca cy E st i m a t es ( 95 % C I ) A p r i l 30 , 1 99 8 A p r i l 20 , 1 99 9 A l l A O M E p i so d es 6. 4% ( 3 .9 % , 8 .7 % ) 5. 9% ( 3 .8 % , 7 .9 % ) F i r s t A O M E p i so d e 4. 9% ( 2 .3 % , 7 .5 % ) 4. 4% ( 2 .1 % , 6 .7 % ) F i r s t E a r T u b e P l ac em en t 20 . 6% ( 4 .0 % , 3 4 .3 % ) 23 . 2% ( 1 1 .3 % , 3 3 .5 % ) F r eq u en t A O M 9. 2% ( 4 .3 % , 1 3 .9 % ) 10 . 2% ( 6 .3 % , 1 3 .9 % ) R u p t u r ed E ar , V ac ci n e S ero t y p e 57 . 1% ( 1 8 .7 % , 8 6 .5 % ) 66 . 7% ( 1 2 .3 % , 8 9 .2 % ) Summary of Efficacy Estimates (ITT) Oute Finnish NCKP Vaccine Serotypes 54% NA First Episode Vaccine Serotypes 48% NA All S. pneumo, Culture Confirmed 32% NA Recurrent OM* 9%** 9% Tympanostomy Tube 4%** 21% All Cause OM 4%** 6% First Episode All Cause AOM NA 5% * All cause otitis media ** Not statistically significant at p= NA = Not available Finnish Otitis Media Study: Safety Analysis Finnish OM Study: Safety Analysis Relevance of safety data to US population is limited: ? Use of concurrent DTwPHib bination vaccines for first 3 doses, rather than DTaP, plicates assessments of systemic reactions ? Homogeneous study population ? Study not large enough to detect unmon adverse events Finnish OM Study: Safety Analysis, Local and Systemic Reactions, First 3 Doses D o s e 1 D o s e 2 D o s e 3 Pn c C R M N = 8 2 5? % H BV N = 8 2 5? % p v a l u e1 Pn c C R M N = 8 1 8? % H BV N = 8 2 6? % p v a l u e1 Pn c C R M N = 8 1 7? % H BV N = 8 1 6? % p v a l u e1 F e v e r ? 38 ? C 1 4 . 3 9 . 3 0 . 0 1 1 8 . 4 1 2 . 7 0 . 0 1 2 3 . 5 1 3 . 3 0 . 0 1 F e v e r ? 39 ? C 0 . 4 0 . 2 1 1 . 0 0 . 5 0 . 3 8 2 . 0 0 . 5 0 . 0 1 C ry i n g i n c r e a s e d 4 1 . 6 3 6 . 4 0 . 0 3 4 2 . 0 3 2 . 9 0 . 0 1 3 9 . 6 3 0 . 6 0 . 0 1 C ry i n g 4 h rs 0 . 6 0 . 4 0 . 7 2 0 . 5 0 . 1 0 . 3 7 0 . 4 0 . 1 0 . 6 2 Pa i n 3 . 4 1 . 9 0 . 0 9 3 . 7 0 . 7 0 . 0 2 5 . 1 2 . 8 0 . 0 2 R e d n e s s (An y ) 1 4 . 2 9 . 3 0 . 0 1 1 6 . 0 1 2 . 6 0 . 0 6 2 0 . 0 1 5 . 9 0 . 0 2 ? 2 . 5 c m 0 0 . 1 1 0 . 2 0 . 2 0 . 6 2 0 . 4 0 . 0 0 . 2 5 Sw e l l i n g ( An y ) 4 . 7 1 . 7 0 . 0 1 4 . 0 3 . 0 0 . 1 6 4 . 8 3 . 6 0 . 1 9 ? 2 . 5 c m 1 . 0 0 . 1 1 0 . 9 0 . 4 0 . 3 3 0 . 5 0 . 2 0 . 6 8 ? N u m b e r o f s u b j e c t s m a y v a ry s l i g h t l y d e p e n d i n g o n r e p o rt s re c e i v e d . 1 P v a l u e b a s e d o n C h i s q u a r e t e s t . Finnish OM Study: Safety Analysis, Local and Systemic Reactions, 4th Dose D o s e 4 ( 1 2 m o n t h s ) P n c C R M N = 79 8? % HBV N = 79 8? % p v a l u e1 1 1 . 5 6 . 9 0 . 0 1 F e v e r ? 38 ? C ? 39 ? C 1 . 6 1 . 7 0 . 9 7 2 8 . 2 1 9 . 3 0 . 0 1 C r y i n g i n c r e a s e d C r y i n g 4 h o u r s 0 0 NA P a i n 7 . 5 2 . 3 0 . 0 1 1 4 . 7 1 4 . 4 0 . 6 0 R e d n e s s ( A n y ) ? 2 . 5 c m 0 . 8 0 . 0 0 . 0 4 4 . 9 5 . 4 0 . 8 3 S w e l l i n g ( A n y ) ? 2 . 5 c m 1 . 3 0 . 4 0 . 0 9 1 p v a l u s d e r i v e d f r o m C h sq u a r e t e st . ? To t a l n u m b e r m o n i t o r e d v a r i e d f r o m 7 7 1 7 9 8 , d e p e n d i n g o n n u m b e r o f co m p l e t e d r e p o r t s r e c e i v e d . Finnish OM Study: Safety Analysis, Conclusions ? Safety data are consistent with earli