A Prospective, Single-arm, Multicenter Study to Evaluate Effectiveness and Safety of Tympanostomy Tube Placement Using the Tula Iontophoresis and Tube Delivery Systems for Children in an Office Setting.
Phase: PHASE3
Conditions: OME - Otitis Media With Effusion, AOM - Acute Otitis Media
Sponsor: Tusker Medical

T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 1  of 8 1  
 
 
A P R O S P E C TI V E, SI N G L E -A R M, M U L TI C E N T E R S T U D Y T O 
E V A L U A T E E F F E C TI V E N E S S A N D S A F E T Y O F T Y M P A N O S T O M Y 
T U B E P L A C E M E N T U SI N G T H E T U L A I O N T O P H O R E SI S A N D T UB E 
D E LI V E R Y S Y S T E M S F O R  C HI L D R E N I N A N  O F FI C E  S E T TI N G  
( O T T ER ; in -O ffice T y m pa n ost o m y T u be place m E nt i n c hil dR e n) 
 
 
St u d y Pr o d uct s: 
•  T U L A I o nt o p h oresis S yste m,  
•  2 % Li d o cai ne  H Cl /1: 1 0 0, 0 0 0 E pi ne p hri ne  
 
•  a n d T U L A T u b e Deli ver y S yste m  
 
 
St u d y P has e:  Pi v otal  
 
Pr ot oc ol #:  C P R 0 0 7 0 0 1  
Re visi o n: E  
 
I D E N u m ber : G 1 7 0 1 9 3  
N C T N u m ber: N C T 0 3 3 2 3 7 3 6  
 
 
S P O N S O R:  
T us ker Me dic al , I nc. 
1 5 5  J effers o n Dri ve  
Me nl o Par k, C A 9 4 0 2 5  
U S A  
 
 
 
M E DI C A L M O NI T O R S : 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
T his pr ot oc ol c o ntai ns c o nfi de ntial i nf or mati o n f or use b y i n v esti gat ors p artici pati n g i n t his 
st u d y a n d s h o ul d be mai ntai ne d i n a sec ure l ocati o n. It s h o ul d n ot be d u plicate d or ma de 
a vaila ble f or re vie w b y a n y u na ut h orize d pers o n or fir m . 

T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2  of 8 1  
A P R O S P E C TI V E, SI N G L E -A R M, M U L TI C E N T E R S T U D Y T O E V A L U A T E 
E F F E C TI V E N E S S A N D S A F E T Y O F T Y M P A N O S T O M Y T U B E P L A C E M E N T U SI N G 
T H E T U L A I O N T O P H O R E S I S A N D T U B E D E LI V E R Y S Y S T E M S F O R C HI L D R E N I N 
A N O F FI C E S E T TI N G  ( O T T E R; i n-O ffice T y m p a n ost o m y T u be place m E nt i n c hil d R e n) 
 
Pr ot oc ol N u m ber: C P R 0 0 7 0 0 1  
 
A p pr o ve d B y:  
 
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Date  
 
 
 
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Date  
 
 
 
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Date  
 
 
 
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Date  
 
 
 
 
 

T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3  of 8 1  
T A B L E  O F  C O N T E N T S  
 
T A BL E O F C O N T E N T S  ........................................................................................................................................ 3  
1. 0  
IN V E S TI G A T O R S  ........................................................................................................................................ 7  
2. 0  
S T A T E M E N T O F C O M PLI A N C E  ...................................................................................................................... 7  
3. 0  
IN V E S TI G A T O R S I G N A T U R E P A G E  ................................................................................................................. 8  
4. 0  
L I S T O F A B B R E VI A TI O N S  ............................................................................................................................. 9  
5. 0  
P R O T O C OL S U M M A R Y  ............................................................................................................................. 1 0  
6. 0  
B A C K G R O U N D IN F O R M A TI O N A N D S CI E N TI FI C R A TI O N AL E  .............................................................................. 1 6  
6. 1.  
C LI NI C AL A N D T E C H N OL O G Y B A C K G R O U N D  ................................................................................................. 1 6  
7. 0  
S T U D Y D E VI C ES  ...................................................................................................................................... 2 0  
7. 1.  
D E VI C E D E S C RI P TI O N S  ............................................................................................................................. 2 0  
7. 1. 1.  
IO N T O P H O R ESI S S YS T E M .......................................................................................................................... 2 0  
7. 1. 2.  
IO N T O P H O R ESI S B ASI C O P E R A TI N G P RI N CI PL E S  ............................................................................................ 2 5  
7. 1. 3.  
T U B E D ELI V E R Y S YS T E M ( T D S).................................................................................................................. 2 6  
 
 ......................................................................................................................................... 2 8  
 
  
 
  
 
 ............................................................... 2 8  
9. 0  
T U S K E R M E DI C AL C LI NI C AL E X P E RI E N C E  ...................................................................................................... 2 9  
1 0. 0  
S T U D Y D E SI G N ....................................................................................................................................... 3 0  
1 0. 1.  
S T U D Y O BJ E C TI V E  ................................................................................................................................... 3 0  
1 0. 2.  
O V E R ALL S T U D Y D E SI G N –  P H AS E S A N D E N R OLL M E N T  ................................................................................... 3 0  
1 0. 3.  
D E SI G N O F T H E P I V O T AL S T U D Y P H A S E  ....................................................................................................... 3 1  
 
  
 
 ........................................................................... 3 3  
1 0. 3. 1. 1.  P R O C E D U R AL S U C C E SS  ............................................................................................................................ 3 3  
1 0. 3. 1. 2.  T U B E P L A C E M E N T T OL E R A BILI T Y  ................................................................................................................ 3 4  
1 0. 4.  
S T U D Y P O P UL A TI O N  ................................................................................................................................ 3 6  
1 0. 4. 1 . D E FI NI TI O N O F E N R OLL M E N T  .................................................................................................................... 3 6  
1 0. 4. 2.  S T U D Y C O H O R T D E FI NI TI O NS .................................................................................................................... 3 6  
1 0. 4. 2. 1.  L E A D -IN O R  C O H O R T  .............................................................................................................................. 3 6  
1 0. 4. 2. 2.  L E A D -IN O F FI C E C O H O R T  ......................................................................................................................... 3 6  
1 0. 4. 2. 3.  P I V O T AL C O H O R T  ................................................................................................................................... 3 6  
1 0. 5.  
P RI M A R Y E N D P OI N T S  .............................................................................................................................. 3 6  
1 0. 6.  
S A F E T Y E N D P OI N T  .................................................................................................................................. 3 8  
1 0. 7.  
S E C O N D A R Y E F F E C TI V E N E S S E N D P OI N T S  ..................................................................................................... 3 8  
1 0. 7. 1.  T U B E P A T E N C Y  ....................................................................................................................................... 3 8  
1 0. 7. 2.  T U B E R E T E N TI O N  .................................................................................................................................... 3 8  
1 0. 7. 3.  A N E S T H E SI A E F F E C TI V E N E S S ..................................................................................................................... 3 9  
 
 ................................................................................................................................. 3 9  
 
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 ......................................................................... 4 0  
 
...................................................................... 4 1  
 ............................................................... 4 1  
  
 
 ........................................... 4 1  
 
 .................................................................. 4 1  
1 0. 9.  
IN CL U SI O N C RI T E RI A  ................................................................................................................................ 4 1  
1 0. 1 0.  E X CL USI O N C RI T E RI A  ............................................................................................................................... 4 2  

T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4  of 8 1  
1 1. 0  
S T U D Y P R O C E D U R E S  ............................................................................................................................... 4 3  
1 1. 1.  
IN V E S TI G A T O R T R AI NI N G  .......................................................................................................................... 4 3  
1 1. 2.  
L E A D -IN P R O C E D U R ES  ............................................................................................................................. 4 3  
 
 ................................................................................................................ 4 4  
1 1. 4.  
E V AL U A TI O N M E T H O D S ........................................................................................................................... 4 4  
1 1. 4. 1.  D I A G N O SI S ............................................................................................................................................ 4 4  
1 1. 4. 2.  C O N C O MI T A N T M E DI C A TI O N S  .................................................................................................................. 4 5  
1 1. 4. 3.  C R A NI AL N E R V E P H YSI C AL E X A M  ............................................................................................................... 4 5  
1 1. 4. 4.  O T O S C O P Y  ............................................................................................................................................ 4 5  
1 1. 4. 5.  T Y M P A N O M E T R Y  .................................................................................................................................... 4 6  
1 1. 4. 6.  A U DI O M E T R Y  ......................................................................................................................................... 4 6  
1 1. 4 . 7. A N E S T H E SI A E F F E C TI V E N E S S ..................................................................................................................... 4 6  
1 1. 4. 8.  T OL E R A BILI T Y ( F P S-R)  ............................................................................................................................ 4 7  
1 1. 4. 9.  T OL E R A BILI T Y ( FL A C C)............................................................................................................................ 4 7  
1 1. 4. 1 0.  P A R E N T / GU A R DI A N S U R V E Y  ..................................................................................................................... 4 9  
1 1. 5.  
S U BJ E C T R E C R UI T M E N T A N D INF O R M E D C O N S E N T  ........................................................................................ 4 9  
1 1. 6.  
S C R E E NI N G E V AL U A TI O N S  ........................................................................................................................ 5 0  
1 1. 7.  
P R O C E D U R E ........................................................................................................................................... 5 0  
1 1. 7. 1.  O T O S C O PI C E X A MI N A TI O N A N D E A R P R E P A R A TI O N  ....................................................................................... 5 0  
1 1. 7. 2.  E A R S E T S I ZI N G ....................................................................................................................................... 5 0  
1 1. 7. 3 . A N E S T H E TI C S OL U TI O N P R E P A R A TI O N  ........................................................................................................ 5 0  
1 1. 7. 4.  E A R S E T P L A C E M E N T A N D D R U G IN S TILL A TI O N  .............................................................................................. 5 0  
1 1. 7. 5.  S T A R T O F IO N T O P H O R ESI S  ........................................................................................................................ 5 1  
1 1. 7. 6.  A N E S T H E TI C S OL U TI O N A N D R E T U R N E L E C T R O D E P A T C H R E M O V AL ................................................................. 5 2  
1 1. 7. 7.  P O S T -IO N T O P H O R ESI S A N E S T H ESI A E F F E C TI V E N E S S ....................................................................................... 5 2  
1 1. 7. 8.  T Y M P A N O S T O M Y T U B E P L A C E M E N T ........................................................................................................... 5 2  
1 1. 7. 9.  P O S T -P R O C E D U R E O T OS C O P Y A N D C R A NI AL N E R V E E X A M  ............................................................................. 5 3  
1 1. 7. 1 0.  U N S U C C ES SF UL P R O C E D U R E S  .................................................................................................................... 5 3  
 
 ........................................................................................................................ 5 3  
1 1. 9.  
3 -W E E K P O S T -P R O C E D U R E F OLL O W -U P V I SI T ( +/- 7  D A Y S ) .......................................................................... 5 4  
1 1. 1 0.  6,  1 2,  1 8  A N D 2 4 -M O N T H P O S T -P R O C E D U R E F OLL O W -U P V I SI TS ( +/- 2 8  D A Y S ) .............................................. 5 4  
1 1. 1 1.  S U M M A R Y –  S T U D Y  F L O W A N D S T U D Y E V AL U A TI O N S  .................................................................................... 5 4  
1 2. 0  
A S S E SS M E N T O F S A F E T Y  ........................................................................................................................... 5 6  
1 2. 1.  
A D V E R S E E V E N TS .................................................................................................................................... 5 6  
1 2. 2.  
S E RI O U S A D V E R S E E V E N T S  ....................................................................................................................... 5 7  
1 2. 3.  
A D V E R S E E V E N T D EFI NI TI O N S ................................................................................................................... 5 7  
1 2. 4.  
A D V E R S E E V E N T C L AS SI FI C A TI O N ............................................................................................................... 5 9  
1 2. 5.  
S A F E T Y M O NI T O RI N G  .............................................................................................................................. 6 3  
 
) ......................................................................................................... 6 3  
1 2. 6.  
D E VI C E M AL F U N C TI O N S  ........................................................................................................................... 6 4  
1 3. 0  
S T A TIS TI C AL M E T H O DS  ............................................................................................................................ 6 4  
1 3. 1 . 
G E N E R AL S T A TI S TI C AL M E T H O D S ............................................................................................................... 6 5  
1 3. 2.  
A N AL Y SIS S E TS ....................................................................................................................................... 6 5  
1 3. 2. 1.  F ULL A N AL Y SI S S E T ................................................................................................................................. 6 5  
1 3. 2. 2.  P E R P R O T O C OL S E T ................................................................................................................................. 6 5  
1 3. 2. 3.  S A F E T Y A N AL Y SI S S E T .............................................................................................................................. 6 5  
1 3. 3.  
P RI M A R Y E N D P OI N T A N AL Y SI S  .................................................................................................................. 6 5  
1 3. 4.  
S E C O N D A R Y E F FI C A C Y E N D P OI N T A N AL Y S E S  ................................................................................................ 6 7  
1 3. 4. 1.  T U B E P A T E N C Y  ....................................................................................................................................... 6 7  
1 3. 4. 2.  T U B E R E T E N TI O N  .................................................................................................................................... 6 8  
1 3. 4. 3.  A N E S T H E SI A E F F E C TI V E N E S S ..................................................................................................................... 6 8  
 
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T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 5  of 8 1  
1 3. 6.  
S A F E T Y A N AL Y SI S  .................................................................................................................................... 7 0  
 
 .................................................................................................................... 7 0  
 
 .............................................................................. 7 0  
 
.................................................................... 7 0  
 
 ..................................................................................... 7 0  
 
 .......................................................................... 7 1  
 
 
 
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1 3. 8.  
H A N DLI N G D R O P O U T S O R M I S SI N G D A T A  .................................................................................................. 7 2  
 
 ................................................................................................................................ 7 2  
 
   
 .................................................................................................................................... 7 3  
 
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1 4. 0  
E T HI C S / PR O T E C TI O N O F H U M A N S U BJ E C T S  ................................................................................................. 7 3  
1 4. 1.  
S U BJ E C T C O N FI D E N TI ALI T Y  ....................................................................................................................... 7 3  
1 5. 0  
P R E M A T U R E T E R MI N A TI O N O R W I T H D R A W AL .............................................................................................. 7 3  
1 5. 1.  
S U BJ E C T S T O P PI N G C RI T E RI A  .................................................................................................................... 7 3  
1 5. 2.  
S T U D Y S T O P PI N G C RI T E RI A  ....................................................................................................................... 7 4  
1 6. 0  
IN V E S TI G A T O R R E S P O N SI BILI TI E S ................................................................................................................ 7 5  
1 7. 0  
S P O N S O R  .............................................................................................................................................. 7 6  
1 8. 0  
M O NI T O RI N G  ........................................................................................................................................ 7 6  
1 9. 0  
IN V E S TI G A TI O N AL P R O D U C T A C C O U N T A BILI T Y  .............................................................................................. 7 6  
2 0. 0  
D E VI A TI O N S........................................................................................................................................... 7 6  
2 1. 0  
D A T A H A N DLI N G A N D R E C O R D K E E PI N G ..................................................................................................... 7 7  
2 1. 1.  
S O U R C E D A T A A N D C A S E R E P O R T F O R M S  ................................................................................................... 7 7  
2 1. 2.  
D A T A Q U ALI T Y A S S U R A N C E ...................................................................................................................... 7 7  
2 1. 3.  
R E C O R D R E T E N TI O N ................................................................................................................................ 7 7  
2 2. 0  
P U BLI C A TI O N P OLI C Y  ............................................................................................................................... 7 7  
2 3. 0  
R E F E R E N C E S  .......................................................................................................................................... 7 8  
 
 
 
 

T us ker Me dic al, I nc.  
 
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6  of 8 1  
 
T A B L E S  
 
 
 
 
Ta ble 3. F L A C C Sc ori n g  ......................................................................................................... 4 8  
Ta ble 4. Ta ble of E val uati o ns  .................................................................................................. 5 6  
Ta ble 5. Ta ble of Ear -rel ate d A d vers e E ve nt Se verit y ............................................................ 6 0  
Ta ble 6. Ta ble of Ot her E ve nts A d verse E ve nt Se verit y  ......................................................... 6 1  
Ta ble 7. Ta ble of A d verse E ve nt Ca usalit y  ............................................................................. 6 2  
Ta ble 8. Ta ble of Heari n g T hres h ol d C ha n ge ( W orse ni n g) Classificati o n  ............................. 6 3  
 
 
FI G U R E S  
 
Fi g ure 1.  I o nt o p h oresis C o ntr ol U nit  ...................................................................................... 2 2  
 
Fi g ure 3. Ret ur n El ectr o d e Patc h  ............................................................................................. 2 3  
Fi g ure 4. E ar Pl u g Siz e rs ......................................................................................................... 2 4  
Fi g ure 5. C urre nt Ra m p Pr ofile  ............................................................................................... 2 6  
Fi g ure 6. Sc h e matic of I o nt o p h oresis of t he T M  ..................................................................... 2 6  
Fi g ure 7. T us k er Me dic al T y m pa n ost o m y T u be  ...................................................................... 2 7  
Fi g ure 8. T u b e Deli ver y S yste m  .............................................................................................. 2 7  
 
Fi g ure 1 0. Faces Pai n Scale -Re vise d  ....................................................................................... 4 7  
Fi g ure 1 1. Sc h e matic of St u d y Desi g n Fl o w  ........................................................................... 5 5  
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7  of 8 1  
1. 0   I N V E S TI G A T O R S 
A list of I n v esti gat ors is pr o vi de d wit h t he I n vesti gat or’s  I nf or mati o n a n d will be s u b mitte d 
t o t he F D A a n d I R B. 
 
 
St ate me nts of Q u alific ati o ns:  
Q ualificati o ns of i n vesti gat ors are pr o vi de d i n t he I n v esti gat or I nf or mati o n a n d will b e 
s u b mitte d t o t he F D A a n d I R B. 
 
2. 0  S T A T E M E N T O F C O M P LI A N C E  
T his st u d y will be c o n d u cte d i n acc or da nce wit h a n y s p ecific pr o visi o ns of t he ass ociate d 
I nstit uti o nal Re vie w B o ar d(s) (I R Bs) a n d 2 1 C F R Part s 8 1 2 a n d 3 1 2 . T his st u d y will b e 
c o n d ucte d i n acc or da n ce wit h t he et hical pri nci ples t hat ha ve t heir ori gi n i n t he Declarati o n 
of Helsi n ki a n d t h at are c o nsiste nt wit h G o o d Cli nical Practice ( G C P) , I S O 1 4 1 5 5 a n d t h e 
a p plica ble n ati o nal a n d re gi o n al re g ulat or y re q uir e me nts . S pecificall y, t his st u d y will be 
g ui de d b y t he et hical pri nci ples of T he Bel m o nt Re p ort, t he Declarati o n of Helsi n ki, a n d 
t he Int er nati o nal C o nfere nce f or Har m o nizati o n G o o d Cli nical Practice (I C H -G C P) .  
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 8  of 8 1  
3. 0   I N V E S TI G A T O R SI G N A TU R E P A G E  
I ac k n o wle d ge recei pt of pr ot oc ol a n d c o nfir m I h a ve rea d a n d u n derst o o d its c o nte nts a n d 
a gree t o f ulfill m y o bli gati o ns as descri be d herei n . I will e ns ure t hat t he st u d y is c o n d uct e d 
i n c o m plia nce wit h t he pr ot oc ol a n d all a p plica ble re g ulat or y re q uire me nts. 
 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _   
I N V E S TI G A T O R ( Pri nt Na me)  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
I N S TI T U TI O N 
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
A D D R E S S  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
SI G N A T U R E  
 
 
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _  
D A T E  (D D /M M M /Y Y Y Y ) 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 9  of 8 1  
4. 0   LI S T O F A B B R E VI A TI O N S  
 
 
 
 
A E   
 
 
A d verse E v e nt  
A O M  
 
 
Ac ute Otitis Me dia  
C F R  
 
 
C o de of Fe d eral Re g ul ati o ns  
C R F  
 
 
Case Re p ort F or m  
C T A  
 
 
Cli nical Trial A gree me nt  
d B   
 
 
Deci bels  
D C  
 
 
Direct C urre nt  
DI P S  
 
 
De vice I nitiate d Pa us e Se q ue nce  
E M L A  
 
 
E utectic Mi xt ure of Li d o cai ne  H Cl  a n d Pril ocai n e  
E N T  
 
 
Ear, N ose a n d T hr o at  
F D A  
 
 
F o o d a n d Dr u g A d mi nistrati o n  
F P S -R  
 
 
Faces Pai n Scale - Re vis e d  
F L A C C   
 
Faces, Le gs, Ar ms, Cr y, C o ns ola bilit y Scal e  
G C P  
 
 
G o o d Cli nical Practice  
H Cl  
 
 
H y dr oc hl ori de  
I C H 
 
 
Inter nati o nal  C o nfere nce f or Har m o nizati o n  
I D E 
 
 
I n v esti gati o nal De vice E x e m pti o n 
I F U 
 
 
I nstr u cti o ns F or Us e 
I N D 
 
 
I n v esti gati o nal Ne w Dr u g A p plicati o n  
I O  
 
 
I n Office 
I P S 
 
 
I o nt o p h or esis S yste m 
I R B 
 
 
I nstit uti o nal Re vie w B oar d 
I S O 
 
 
I nter nati o nal Or ga nizati o n f or Sta n dar dizati o n  
L C D  
 
 
Li q ui d -Cr ystal Dis pla y  
Me d R A  
 
 
Me dical Dicti o nar y f or R e g ul at or y Acti vities  
M T T  
 
 
M yri n g ot o m y wit h T y m p a n ost o m y T u be  
N S R  
 
 
N o n -Si g nifica nt Ris k  
O M E  
 
 
Otitis Me dia wit h Eff usi o n  
O R  
 
 
O perati n g R o o m  
P S A  
 
 
Press ure -Se nsi ti ve A d hesi ve 
S A E  
 
 
Seri o us A d verse E v e nt  
S D   
 
 
Sta n dar d De viati o n   
T D S  
 
 
T u be Deli ver y S yste m  
T M  
 
 
T y m pa nic M e m bra n e  
T T   
 
 
T y m pa n ost o m y T u be  
U A D E  
 
 
U na ntici pate d A d verse De vice Effect  
 
 

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Pa ge 1 3  of 8 1  
a nest hesia f or T T place me nt i n all treate d ears as deter mi ne d b y 
p h ysicia n’s e val uat i o n of T M a nest hesia pri or t o t u be place m e nt.  
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
 
 
 
 
 
  
 
 
  
  
 
 
  
  
  
 
 
 
 
 
 
 
 
  
 
  
  
 
  
 
 
  
  
  
  
 
  
  
  
  
 
  
  
 
 
  
  
  
  
 
 
 
 
 
  
 
  
  
 
  
 
 
  
  
  
  
 
  
  
  
  
 
 
 
 
 
 
 
 
 

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6. 0   B A C K G R O U N D I N F O R M A T I O N A N D S CI E N TI FI C RA TI O N A L E  
6. 1.   Cli nic al a n d Tec h n ol o g y B ac k gr o u n d  
Otitis me dia (i nfla m mati o n of t he mi d dle ear) is t he m ost fre q ue nt dia g n osis i n sic k c hil dre n 
visiti n g pe diatricia n offi ces. Se ve nt y -fi ve p erce nt of c hil dre n e x perie n ce at least o n e 
e pis o de of otitis me dia b y t heir t hir d year. 2  
 
Otitis me dia has se veral variati o ns, i ncl u di n g ac ute otitis me dia ( A O M) a n d otitis me dia 
wit h  eff usi o n ( O M E). A O M is c haracterize d  b y ac ute si g ns a n d s y m pt o ms of mi d dle ear 
i nfla m mati o n or i nfecti o n .  O M E is c haracterize d b y t he prese nce of fl ui d i n t he mi d dle ear 
wit h or wit h o ut si g ns or s y m pt o ms of ac ute ear i nfecti o n.  T he hi g hest i nci de nce of A O M 
occ urs bet wee n si x a n d 2 4 m o nt hs of a ge a n d decli nes u ntil a s mall re versal is see n bet wee n 
fi ve a n d si x years of a ge, at t he ti me of s c h o ol e ntr y.3 T here te n ds t o be a hi g her i nci de nce 
of O M E i n y o u n ger t ha n i n ol der c hil dre n, beca use t he E ustac hia n t u be i n y o u n ger c hil dre n 
is s h orter, n arr o w er, a n d m ore h oriz o ntal a n d t h e i m m u ne s yste m is less de vel o pe d . T here 
is als o i ncrease d i nci de nce of O M E ass o ciate d wit h cra ni of acial a n o m alies, cleft palate, a n d 
D o w n s y n dr o m e.  Mi d dle ear eff usi o n ca n res ult i n te m p orar y c o n d ucti ve heari n g l oss a n d 
ne gati vel y i m pact a c hil d’s c o g niti ve, la n g ua ge, a n d e m oti o nal de vel o p me nt.   
 
M ore t ha n 7 5 0 , 0 0 0 t y m p a n ost o m y t u b e pr oce d ures are perf or m e d i n c hil dre n y o u n ger t ha n 
a ge 1 8 a n n uall y i n t he U S t o a d dress rec urre nt A O M or O M E, ma ki n g it o ne of t he m ost 
c o m m o n s ur gical pr oce d ures perf or me d i n c hil dre n. 4 B y a ge 3, al m ost 7 % of all c hil dre n 
will ha ve t y m p a n ost o m y t u bes. 1 O ver 7 5 % of t y m pa n ost o m y t u be pr oce d ures i n t he U S are 
perf or me d f or c hil dre n 1 2 years or y o u n ger, wit h 5 8 % of t u be pr oce d ures f or  c hil dre n less 
t ha n 5 years of a ge.4  O v er 9 5 % of t y m p a n ost o m y t u be i nserti o n pr oce d ures i n c hil dre n are 
perf or me d i n t he o p erati n g r o o m ( O R) u n der ge neral a nest hesia. 4  
 
T he t y pic al M yri n g ot o m y wit h T y m p a n ost o m y T u b e place me nt ( M T T) pr oce d ure i n a c hil d 
i n v ol ves t he f oll o wi n g se q ue nce of e ve nts:  
•  T he c hil d fasts fr o m t he e ve ni n g bef ore t he pr oce d ure a n d is br o u g ht t o t he 
h os pital or a m b ulat or y s ur ger y ce nter .ii 
•  Pre me dicati o n wit h oral mi daz ola m ma y b e pr o vi de d t o cal m t he c hil d pri or t o 
pare ntal se p arati o n. 5 
•  After ge n eral a nest hesia is attai ne d, p r o p h yl acti c a nal gesia t o a d dress p ost-
o perati ve pai n s uc h as rectal aceta mi n o p he n  or i ntra nasal fe nt a n yl is t y picall y 
pr o vi de d. 6 
•  C er u me n cle ara n ce is perf or me d.  
•  Usi n g a m yri n g ot o m y bla de, a n a d e q uatel y siz e d m yri n g ot o m y i n cisi o n is t he n 
ma de, t y pi call y i n t he a nt er oi nferi or p orti o n of t he t y m pa nic me m bra ne.
7 ,8  
•  Fl ui d ma y b e re m o v e d fr o m t he mi d dle ear s pace usi n g s ucti o n. 
•  Usi n g alli gat or f orce ps, t he t y m p a n ost o m y t u b e is ma ni p ulate d a n d t uc ke d i nt o 
t he m yri n g ot o m y i ncisi o n. 
                                                 
ii 2 0 1 7 A S A pre -o p erati ve fasti n g g ui deli nes ra n ge restrict clear li q ui ds f or 2 h o urs, breast mil k f or 4 h o urs, c o w’s mil k, f or m ula a n d li g ht 
meals f or 6 h o urs a n d hea v y or fatt y meals f or 8 h o urs.  

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•  Mi n or a dj ust me nts are t he n ofte n p erf or me d usi n g sta n d ar d ot ol o gic 
micr oi nstr u me nts, s uc h as a R ose n pi c k or alli gat or f orce ps, t o ac hie ve o pti mal  
t u be p ositi o n.9  
•  M ulti ple atte m pts t o place t he t u be m a y be re q uir e d i n a c o nsi dera bl e n u m ber 
of cases. 7  
 
I n a d ult p atie nts a n d ol der c hil dre n, t y m pa n ost o m y t u b es ca n b e place d i n a n offi ce setti n g 
usi n g a v ariet y of l ocal a nest hesia o pti o ns  alt h o u g h n o ne are i n dicate d f or a nest hesia of t he 
ear dr u m. P he n ol (car b olic aci d) is ofte n us e d t o ca use a partial t hic k ness c he mical b ur n 
wit h tiss ue necr osis, w hic h lea ds t o l ocalize d a nest hesia of t he T M. 1 0 Ot her a nest hetics, 
s uc h as E M L A crea m ( E utectic 
Mi xt ure of L ocal A nest hetics, li d ocai ne 2. 5 % a n d 
pril ocai ne 2. 5 %) , li d ocai ne H Cl i njecti o ns, B o nai n’s S ol uti o n (c ocai ne h y dr oc hl ori de, 
me nt h ol, p he n ol)  a n d tetracai ne i njecti o ns are us e d less fre q ue ntl y. 1 1 ,1 2 ,1 3  N o ne of t he l ocal 
a nest hetics e m pl o ye d i n a d ults are re g ul arl y use d wit h s mall c hil dre n, as t he y are all 
ass ociate d wit h disc o mf ort or a le n gt h y o nset i nc o m pati ble wit h pe diatric use.   
 
T here are se v eral p ote ntial a d va nta ges t o pr o vi di n g ot olar y n g ol o gists, or Ear, N ose a n d 
T hr oat ( E N T ) s ur ge o ns, wi t h tec h n ol o g y t h at e na bles i n-office t u be place me nt i n pe diatric  
patie nts. T he peri o perati ve ris ks ass oci ate d wit h t he ge neral a n est hesia re q uire d f or t u b e 
place me nt i n t he O R ca n be a v oi de d wit h a n office -bas e d pr oce d ure. Ge n eral a nest h etic 
c o m plicati o ns occ ur at meas ura ble rates ra n gi n g bet w ee n 1 2. 6 % a n d 1 8 % i n t u be 
pr oce d ures i n c hil dre n. 1 4 ,1 5 Alt h o u g h seri o us a d v erse effects of ge neral a n est hesia d uri n g 
t u be pr oce d ures are u n c o m m o n, t he y ca n b e s e vere i ncl u di n g l ar y n g os pas m, air wa y 
o bstr ucti o n, desat urati o n, d ysr h yt h mia a n d p ost -o p erati ve v o miti n g re q uiri n g treat me nt . 
 
I n a d diti o n, there is a n i ncreasi n g i nterest i n gai ni n g a better u n d ersta n di n g of t he p ote ntial 
f or ne ur o de v el o p me ntal i m pact of ge neral a nest hesia i n s mall c hil dre n.  A gr o wi n g b o d y 
of literat ure 
s u g gest s a li n ka ge 
bet w ee n 
ge n eral 
a nest hesia 
e x p os ure 
a n d 
ne ur o de vel o p me nt al i m pact, t h o u g h it re mai ns diffic ult t o se parat e t he p ost -ge neral 
a nest hesia o utc o mes fr o m t he u n derl yi n g c o n diti o n f or w hic h t he c hil d u n der we nt s ur ger y. 
O ne st u d y s h o we d t h at  c hil dre n w h o recei v e d ge neral a n est hesia b ef ore a ge 3 years were 
a p pr o xi matel y 1. 9 ti mes as li kel y as c o ntr ols t o s h o w la n g ua ge disa bilit y a n d 1. 7  ti mes as 
li kel y t o s h o w c o g niti ve disa bilit y, e ve n aft er a si n gle a n est hetic e x p os ure. 1 6 I n a n ot her 
st u d y, chil dre n wit h a hist or y of m ulti ple e x p os ures t o ge neral a nest hesia bef ore 4 years of 
a ge were s h o w n t o ha ve a si g nifica nt l y i n crease d ris k of de vel o pi n g lear ni n g disa bilities 
c o m pare d t o t h ose w h o h a d  a si n gl e e x p os ure or n o ne .1 7  A rece nt p u blicati o n de m o nstrate d 
a si g nifica nt l oss i n brai n w hite matter f or c hil dre n u n der g oi n g brief a nest hetic e x p os ures 
( 3 0 % of t he st u d y sa m ple was t y m p a n ost o m y pr oce d ures) as c o m pare d t o n o n-e x p ose d 
c o ntr ols .1 8 A n ot her rece nt s t u d y s h o ws t hat a si n gle e x p os ure t o ge n eral a n est hetic fr o m 
c o m m o n a n d mi n or s ur gi cal pr oce d ures is ass ociat e d wit h s mall b ut statisticall y -si g nifica nt 
i ncreas e d ris ks of me ntal dis or der dia g n osis, de v el o p me ntal dela y, a n d atte nti o n deficit 
h y peracti vit y dis or d er .1 9 F D A rece ntl y iss ue d a Dr u g Safet y C o m m u nicati o n war ni n g t hat 
re peat e d use of ge neral a nest hetic a n d se d ati o n dr u gs, or us e f or greater t h a n t hree h o urs, 
i n y o u n g c hil dre n m a y affect t he d e vel o p me nt of c hil dre n’s brai ns.2 0 W hile 
a nest hetic 
e x p os ure d uri n g t y m pa n ost o m y tu be pr oce d ures is us uall y brief,  a p pr o xi matel y 3 0 % of 
c hil dre n recei vi n g t u bes re p orte d t o re q uire a sec o n d pr oce d ure. 2 1 ,2 2 W hile st u dies s u g gest 
a li n k bet wee n ge n eral a nest hesia e x p os ure a n d ne ur o de vel o p me nt, t he  l o n g-ter m effects  
res ulti n g fr o m brief e x p os ures t o ge neral a nest heti cs are u n k n o w n.  
 

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I n a d diti o n, b ot h pre-o perati ve a n xiet y a n d p ost -o perati ve stress be ha vi ors a re c o m m o n i n 
c hil dre n. A re p orte d 5 0 -7 5 % of c hil dre n w h o u n der g o a nest hesia de vel o p si g nifica nt 
be ha vi oral stress bef ore s ur ger y .2 3 I n a st u d y of c hil dre n u n der g oi n g h er nia re p air, 
t y m pa n ost o m y t u be place me nt, t o nsillect o m y, a d e n oi dect o m y ot her ot olar y n g ol ogic a n d 
mi n or pr oce d ures, it w as re p orte d t hat u p t o 5 4 % c hil dre n e x hi bit mala da pti ve be ha vi or 
res p o nses f oll o wi n g s ur ger y i ncl u di n g ge neral a n xiet y, e n uresis, se parati o n a n xiet y a n d 
te m per ta ntr u ms at 2 wee ks p ost o perati vel y , wit h u p t o 4 7 % re p orti n g sleep pr o ble ms. 2 4  
 
T he list bel o w re vie ws r e p orte d distress, pai n a n d me dical t hera pi es re p orte d f or pe diatric 
t y m pa n ost o m y pr oce d ures u n der ge neral a nest hesia. 
 
Pre -O per ati ve:  
•  Pre -o perati ve a n xiet y is c o m m o n a n d n ot i nsi g nifica nt, li kel y e x acer bate d b y t he 
re q uire me nts f or fasti n g.  F or c hil dre n a ge d 2 t o 1 0 years ol d  u n der g oi n g c o m m o n 
electi ve o ut patie nt pr oce d ures, Kai n meas ure d pre -o perati ve a n xiet y at 3 7 ( o n a 1 0 0 -
p oi nt  Vis ual A nal o g ue S cale ( V A S )), w hic h r ose t o 5 7 u p o n pare ntal se parati o n as t he 
c hil d was ta ke n t o t he O R. 1 9 T o a d dress pre -o perati ve a n xiet y  bef ore t y m pa n ost o m y 
pr oce d ures , ma n y i nstit uti o ns re g ularl y a d mi nister mi daz ola m t o t he c hil d.5  O t her 
tec h ni q ues ha ve bee n e m pl o ye d i n t he o perati n g r o o m t o re d uce pre -o perati ve a n xiet y 
s uc h as m usic, vi de os, a n d prese nce of a fa v orite t o y.  
I n d ucti o n: 
•  C hil dre n ofte n e x press distress be ha vi ors d uri n g i n d ucti o n of a nest hesia f or o ut patie nt 
electi ve s ur ger y.  E v e n wit h  a pare nt pres e nt f or a n est hesia i n d ucti o n, C h or ne y  
de m o nstrate d t hat greater t ha n 4 0 % of c hil dre n  a ge d 2-1 0 years ol d  dis pla y clear 
distress be ha vi ors d uri n g i n d ucti o n, wit h 1 7 % dis pla yi n g si g nifica nt distress a n d m ore 
t ha n 3 0 % of c hil dre n resisti n g a n esthesi ol o gists d uri n g i n d ucti o n. 2 5  O n a vis ual 
a nal o g ue scale, pare nts of c hil dre n ( 5. 8 year -ol d mea n) u n der g oi n g o ut patie nt s ur ger y 
rate d t he c hil d’s i n d ucti o n a n xiet y as a mea n sc ore of 4 0. 0 ( o ut of 1 0 0).2 6 Sa de g hi e t al 
has  s h o w n s o me s uccess i n re d uci n g p re-o p erati ve pe diatric a n xiet y b y ha vi n g t he 
pare nt pr ese nt  d uri n g i n d ucti o n .2 7 
I ntr a-O per ati ve:  
•  Des pite t he bre vit y of t he pr oce d ure, i ntra -o p erati ve c o m plicati o ns occ ur fr o m t he 
a d mi nistrati o n of t he ge neral a nest h etic f or  p e diatric  t y m pa n ost o m y pr oce d ures.  
N ota bl y, lar y n g os p as m ( 0. 8 %), desat ur ati o n ( 0. 3 %), d ysr h yt h mia ( 0. 2 % -1. 8 %), se vere 
air wa y o bstr ucti o n ( 1. 4 %), i ntra -o perati ve v o miti n g ( 0. 4 %) a n d 
mil d air wa y 
o bstr ucti o n ( 1 2 %) ha v e bee n re p orte d i n p e diatric t y m p a n ost o m y t u b e pr oce d ures 
perf or me d u n der  ge neral a nest hesia. 1 4, 1 5 
•  I n a d diti o n t o t he ge n eral a nest h etic, it is c o m m o n practice at ma n y i nstit uti o ns t o 
a d mi nister a d diti o nal s yste mic a ge nts  bef ore pe diatric t y m pa n ost o m y pr oce d ures  t o 
c o ntr ol na usea a n d p ost -o perati ve pai n.  F or e x a m ple, sta n dar d practice at C hil dre n’s 
H os pital of P hila del p hia ( C H O P) is t o a d mi nister s yste mic ket or ol ac, fe nta n yl, or 
b ot h. 2 8  
 

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P ost -O per ati ve Rec o v er y I n H os pit al/ A S C:  
•  9 1 % of c hil dre n  ( 2-1 1 years ol d)  d e m o nstrate distress be ha vi or i n rec o ver y aft er 
electi ve o ut patie nt s ur ger y. 2 9 
•  Des pite recei vi n g rectal aceta mi n o p he n a n d i ntra -nasal de x me det o mi di ne or fe nta n yl 
a n d half t he s u bjects recei vi n g oral mi daz ola m, F L A C C sc ores after o ut patie nt 
t y m pa n ost o m y s ur ger y f or c hil dre n a ge d 1 t o 8 years ol d ra n ge d fr o m 2. 8-4. 8  ( o ut of a 
t otal p ossi ble sc ore of 1 0) fiftee n mi n utes after arri val t o t he rec o ver y war d.6 
•  E mer ge nce a gitati o n, defi ne d as at le ast t hree mi n utes of t hr as hi n g be h avi or re q uiri n g 
restr ai nt, is see n i n 2 7-5 7 % of c hil dre n  ( mea n a ge 2. 6-3. 5 years ol d)  after 
t y m pa n ost o my t u b e pr oce d ures. 3 0 
•  After bilateral t y m p a n ost o m y t u b e place me nt, 1 3 -2 7 % of c hil dre n  a ge d 9 m o nt hs t o 6 
years ol d  v o mit d uri n g rec o ver y. 3 1 
•  A d mi nistrati o n of o pi oi ds occ urs i n s o me facilities t o a d dress p ost -o perati ve 
distress/ pai n.  F or e x a m ple, a rece nt lar ge st u d y fr o m C hil dre n’s 
H os pital of 
P hila del p hia s h o ws o x yc o d o ne a d mi nistrati o n i n 1 8 % of c hil dre n  ( 6 m o nt hs t o 7 years 
ol d)  i n t he rec o ver y r o o m after t u be place me nt.2 3 I n Britis h C ol u m bia’s C hil dre n’s 
H os pital, 1 0 % of c hil dre n  (a ge d 1. 4 t o 6 years ol d) recei v e d c o dei ne i n t he rec o v er y 
r o o m, des pite hi g h-d ose ( 4 0 m g/ k g) oral acet a mi n o p he n recei ve d b y all p atie nts pre -
o perati vel y. 3 2  
P ost -O per ati ve Rec o v er y a t H o me: 
•  After ele cti ve o ut patie nt s ur ger y, Kai n de m o nstr ate d t hat 6 7 % of c hil dre n  a ge d 1-7  
years ol d  e x hi bit ne w ne gati ve be ha vi ors 1 d a y after s ur ger y, wit h 4 5 % c o nti n ui n g t o 
de m o nstrate ne gati ve b e h a vi or c ha n ges 2 da ys after s ur ger y. 3 3  I n 2 3 % of c hil dre n, t hese 
be ha vi ors persiste d 2 wee ks after s ur ger y.  T he b e ha vi ors i ncl u de d wa ki n g u p cr yi n g, 
te m per ta ntr u ms a n d a n i ncreas e d fear of d oct ors a n d h os pitals.  Si milarl y, K oti nie mi 
de m o nstrate d be ha vi oral pr o ble ms after r o uti ne E N T s ur ger y i n 6 1 % of c hil dre n  a ge d 
2 -1 0 years ol d , wit h 3 2 % persisti n g t o 1 m o nt h aft er s ur ger y.3 4   
•  After o ut patie nt bi lateral t y m p a n ost o m y pr oce d ures at t he C hil dre n’s H os pital of 
P hila del p hia , 2 9-5 2 % of c hil dre n ( 9 m o nt hs t o 6 years ol d) e x perie nce d  v o miti n g wit hi n 
t he first 2 4 h o urs.2 6 
 
T us ker Me dical  has t w o tec h n ol o gies de vel o pe d  wit h t he i nte nt  t o e na ble safe a n d relia bl e 
place me nt of t y m p a n ost o m y t u bes i n p e diatric p atie nts i n a n office setti n g wit h l ocalize d 
a d mi nistrati o n of a nest hetics t o t he t y m p a nic me m bra ne . T he tec h n ol o gies t h us pr o vi de t he 
ca pa bilit y t o p ote ntiall y re d uce t he ris ks a n d si de effects of ge neral  a nest h esia, re d uce t he 
patie nt a n d pare ntal a n xiet y t hat ca n be ass oci ate d wit h O R -base d pe diatric pr oce d ures, a n d 
m o ve pr oce d ures t o a l o wer c ost setti n g.  T h e dat a fr o m t his st u d y will hel p i nf or m w het her 
t he T U L A pr oce d ure is s uccessf ul i n e n a bli n g a l ow -distress pr oce d ure wit h a fa v ora ble 
safet y pr ofile. 
 
T he t w o tec h n ol o gies c o nsist of a T u be Deli ver y S yste m ( T D S) a n d a n  I o nt o p h oresis 
S yste m (I P S). T h e T D S is a me c ha nical de vice t h at ra pi dl y p erf or ms a m yri n g ot o m y a n d 
deli vers a prel oa d e d t y m pa n ost o m y t u be wit h si n gle -b utt o n act uati o n. T he I P S is a si n gle -
use micr o pr ocess or -c o ntr olle d direct c urre nt ( D C) ge n erat or use d pr i or t o t he T D S t o 
facilitate a n est hesia of  t h e t y m pa ni c me m bra n e b y dri vi n g i o ns of li d ocai ne a n d e pi ne p hri n e 
i nt o t he tiss ue.  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 0  of 8 1  
7. 0    S T U D Y D E VI C E S  
T us ker 
Me dical , I nc. h as a n I o nt o p h or esis S yste m t hat dri ves i o ns of li d ocai ne a n d 
e pi ne p hri ne i nt o t he t y m pa nic 
me m bra n e t o pr o vi de l ocal a nest hesi a t o facilitate 
t y m pa n ost o m y t u be i nserti o n. T he I o nt o p h or esis S yste m c o nsists of a n I o nt o p h oresis 
C o ntr ol U nit, I o nt o p h oresis Earsets a n d a ret ur n el ectr o de p atc h. T he C o ntr ol U nit m o nit ors 
a n d deli vers a fi x e d a m o u nt of c har ge (ie, d ose) t o t he patie nt t hr o u g h t he Earsets(s) a n d 
alerts t he o p erat or w h e n c har ge deli ver y is c o m pl ete. 
 
 
   
 
T us ker Me dical , I nc. has a T u be Deli ver y S yste m i nte n de d t o pr o vi de a mea ns t o create a 
m yri n g ot o m y wit h i nserti o n of a prel o a de d t y m pa n ost o m y t u be.  T he d esi g n a n d o perati o n 
of t he T D S is i nte n de d t o sta n dar dize t he s ur gical a p pr o ac h t o t y m p a n ost o m y t u be 
place me nt w here b y u p o n act uati o n of t he T D S, a m yri n g ot o m y is create d a n d a T us ker 
Me dical t y m p a n ost o m y tu be is place d nearl y si m ulta ne o usl y ( wit hi n 5 0 0 ms). T he T D S 
de vice c o m bi nes 
m yri n g ot o m y creati o n a n d t u be i nserti o n i nt o o ne strai g htf or war d 
pr oce d ure ste p, t h us a v oi di n g t he nee d t o pass a n e x p ose d s ur gical bla de t h o u g h t he ear 
ca nal of a n a w a ke pe di atric patie nt.   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
7. 1.  De vice Desc ri pti o n s 
7. 1. 1.  I o nt o p h o resis S yste m 
I o nt o p h or esis uses l o w-l e vel electric c urre nt t o direct  m o ve me nt of dr u g i o ns i nt o tiss ue 
t hr o u g h s ki n or m uc osal s urfaces. 
 
 
 T he I P S e m pl o ys a l o w-le vel electric c urre nt t o tra ns p ort 
t he i o nic dr u g, a n d ma y b e perf or me d u nilaterall y or bilaterall y. T h e I P S is batter y -p o were d  
a n d deli vers 6. 4 m A -mi n utes of c har ge at a c urre nt of 0. 8 m A ( ma x i m u m) t o eac h c h a n nel.  
 
T he I P S  is a si n gle us e d e vice a n d c o nsists of t hr ee c o m p o ne nts: a n I o nt o p h oresis C o ntr ol 
U nit, I o nt o p h oresis Ears ets a n d a Ret ur n Electr o de Patc h. F or  bilateral dr u g deli ver y, t w o 
I o nt o p h or esis Ears ets are re q uir e d. Access ories t o t he I o nt o p h oresis S yste m i ncl u de a 
S yri n ge a n d Ears et Siz ers. All c o m p o n e nts of t he I P S  are pr o vi de d n o n -sterile a n d n o 
steriliz ati o n is re q uire d. All patie nt c o ntact 
material s ha ve bee n assesse d f or  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 1  of 8 1  
bi oc o m pati bilit y per I S O 1 0 9 9 3. I o nt o p h oresis wit h t he I P S ma y b e perf or m e d u nilaterall y 
or bilaterall y, a n d bilat eral i o nt o p h oresis 
ma y be perf or me d eit her s e q ue ntiall y or 
si m ulta ne o usl y. 
 
•  T he E arset Sizers  are use d t o deter mi ne t he Earset siz e t hat best fits t he patie nt’s 
a nat o m y. T h e y are c ol or -c o de d t o c orres p o n d t o eac h Earset siz e. C o nsec uti ve siz es are 
m o u nte d at eac h e n d of a  ha n dle a n d la bele d wit h a siz e n u m ber ( Siz e 1 t hr o u g h Size 
6) . T he y are a re usa bl e access or y re q uire d t o deter mi ne t he Earset siz e f or t he ear ca nal 
re q uiri n g treat me nt. 
 
•  T he E arset  i ncl u des an  E ar Pl u g wit h Press ure -Se nsiti ve A d hesi ve ( P S A) attac he d t o a 
ha n dle, a n i nte grate d fill s yste m, a n electrical c o n n ect or , a n d a n i nte grate d ear electr o d e 
t hr o u g h w hic h ele ctrical c urre nt is deli vere d t o t he dr u g s ol uti o n. T he i nte grate d fill 
s yste m all o ws f or t he a d mi nistrati o n of dr u g s ol uti o n wit h t he electr o de i n sit u f or t he 
i nitial fill of t he e xter nal ear ca nal a n d f or t he i ntra -pr oce d ure deli ver y of a d diti o n al 
dr u g s ol uti o n t o t he e xter nal ear ca nal, as n ee de d. M ulti ple Earset  siz es are a vaila ble t o 
acc o m m o date vari ati o n i n patie nt a nat o m y  a n d are c ol or -c o d e d t o c orres p o n d t o t he 
Earset Siz ers.  T he ra n ge of ear pl u g siz es is a p pr o priate f or b o t h pe diatri c a n d a d ult 
patie nts . 
 
•  T he C o ntr ol U nit  pr o vi des t w o i n de pe n de nt c ha n nels of el ectrical c urre nt t o t he 
s ol uti o n i n t he ear ca nal a n d t o a si n gle s hare d ret ur n electr o de  pat c h . T he C o ntr ol U nit 
m o nit ors a n d deli vers a fi x e d a m o u nt of c har ge a n d alerts t he o p erat or w he n c urre nt 
deli ver y is c o m plete.  
 
•  T he Ret ur n Electr o d e P atc h  attac hes t o t he patie nt’s s ki n at a l ocati o n re m ote fr o m 
t he ears t o c o m plete t he electrical circ uit an d is c o n necte d t o t he Earset  a n d C o ntr ol 
U nit via t he ret ur n el ectr o de s na p.  
 
•  T he S yri n ge  is a si n gle use de vice t hat all o ws f or a d mi nistrati o n of dr u g s ol uti o n 
t hr o u g h t he Earset i nt o t h e ear ca n al. 
 
 
I o nt o p h oresis C o ntr ol U nit 
 
T he h a n d hel d I o nt o p h or esis C o ntr ol Unit ( C o ntr ol U nit ) is a si n gle-use micr o pr ocess or -
c o ntr olle d direct c urre nt ge n erat or, as s h o w n i n Fi g ure 1 . It is c o n necte d t o o ne or t w o 
E arsets  a n d t he Ret ur n Electr o de P atc h  via t he el ectrical c o n n ect ors a n d ret ur n electr o d e 
s na p, res pecti vel y. T he C o ntr ol U n it ca n deli ver c urre nt t o a patie nt’s left a n d ri g ht ears 
se q ue ntiall y or si m ulta ne o usl y, if desire d. T he C o ntr ol U nit i ncl u des e m be d de d s oft ware 
t hat deli vers a n d re g ulat es b ot h c urre nt a n d acc u m ulate d c har ge a nd alerts t he o perat or 
w he n c urre nt deli ver y is c o m plete.  
 
T he user i nterface wit h t h e C o ntr ol U nit  c o nsists of t w o p us h b utt o ns a n d a vis ual i n dic at or 
of c ycle pr o gress ( pr o gress bars).    Eac h p us h b utt o n is use d t o i n de pe n de ntl y o perate o ne 
E arset . Eac h p us h b utt o n ca n start, pa use or res u m e c urre nt t o o ne E arset . P us h b utt o ns are 
c ol or c o d e d ( Yell o w  a n d Bl ue) t o i d e ntif y t he E arset  si de t he y c o ntr ol. T h e pr o gress b ars  
are use d t o m o nit or i o nt o p h oresis pr o gress a n d alert t he o perat or of vari o us de vice sta tes. 
T he I P S 2. 0 i ncl u d es a ‘ Re d uce’ feat ure t o all o w t he user t o o pti o nall y a n d te m p oraril y  
re d uce t he c urre nt le vel b y 2 5 % if a s u bject e x perie nces disc o mf ort d uri n g i o nt o p h oresis. 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 2  of 8 1  
If t he Re d u ce feat ure is use d b y t he o p erat or, t he de vice trac ks o v erall c h ar ge, e ns uri n g 
t otal n o mi nal c har ge/ d os e is deli vere d. 
 
 
Fi g ure 1 .  I o nt o p h oresis C o ntr ol U nit 
 
 
I o nt o p h oresis E ar set  
 
T he I o nt o p h oresis Earset ( E arset) is s h o w n i n Fi g ure 2 . It i ncl u des a n ear pl u g attac h e d t o 
a ha n dle, a n i nte grate d fill s yste m, a n d a n i nte grate d electr o de a n d ca ble t hr o u g h w hic h 
electrical c urre nt is deli v ere d t o t h e dr u g s ol uti o n. T he ear pl u g pr o vi des a seal t o kee p t he 
dr u g s ol uti o n i n t he ear ca nal. T h e s urface of t h e ear pl u g is c oat e d wit h a s oft pre ss ure 
se nsiti ve s ki n a d hesi ve t hat sec ures it i n t he ear ca nal d uri n g t he pr oce d ure a n d hel ps 
mai ntai n a seal d uri n g t he pr oce d ure. T he P S A is partiall y c o vere d b y a pr otecti ve li ner t o 
facilitate pla ce me nt of t h e ear pl u g i n t he ear ca n al. T his li ner is peele d off o nce t he ear 
pl u g is i n place. A s oft press ure a p plicat or 
m o u nte d i nsi de t he ear pl u g e na bles 
circ u mfere ntial a d h esi o n of t he P S A c o ate d ear pl u g t o t he ear ca nal s urface b y all o wi n g 
t he user t o a p pl y press ure b y m o vi n g t he ha n dle. T he ear pl u g a ls o i nc or p orates a peel fla p 
feat ur e, w hic h is use d t o peel t he a d heri n g ear pl u g off t he ear ca n al s urface at t he e n d of 
t he pr oce d ure. Si x c ol or-c o de d E arset siz es are a v aila ble t o acc o m m o date variati o n i n ear 
ca nal siz e. F or bilat eral dr u g d eli ver y, t w o Earsets are re q uire d.   
 
T he i nte grat e d fill s yst e m all o ws f or t he a d mi nistrati o n of a dr u g s ol uti o n t o t he ear ca nal, 
as nee de d. At o ne e n d, t he i nte grate d fill s yste m c o ntai ns a ce ntral fill l u me n wit h a bl u nt 
ti p t hr o u g h w hic h t he dr u g s ol uti o n ma y be a d mi nistere d . At t he ot h er e n d of t he i nte grate d 
fill s yste m, a sta n dar d l uer l oc k e na bles m ati n g wit h t he i ncl u de d Syri n ge . 
 
 
T he  ele ctrical ca ble a n d fill s yste m t u bi n g are c oile d t o get her, a n d a cli p is 
pr o vi de d t o sec ure t he t u bi n g t o t he patie nt’s cl ot hi n g, a n d t here b y all o w f or r o uti n g be hi n d 
t he patie nt’s ear.  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 4  of 8 1  
 
Syri n ge  
 
T he Syri n ge  is a sta n d ar d 1 0 cc s yri n ge wit h a c o m pati ble L uer L oc k ti p. 
 
E ar set Sizer  
 
T he E a rset Sizers , s h o w n i n Fi g ure 4 , c o me i n si x siz es ( Size 1  t hr o u g h Size 6 ). T his 
access or y is utilize d t o deter mi ne t he E ar set siz e f or eac h ear ca nal. E ac h E arset  has a 
c orres p o n di n g E ar set Siz er  of t he s a me c ol or.  
 
C o nsec uti ve siz es are m o u nte d at eac h e n d of t he ha n dle a n d la bele d wit h t he a p pr o priat e 
siz e n u m ber ( Siz e 1 t hr o u g h Siz e 6). T he y are a re usa ble access or y re q uir e d t o deter mi ne 
t he Earset size f or t he ear ca nal r e q uiri n g treat me nt.  
 
 
Fi g ure 4 . E ar Pl u g Sizers  
 
 
I o nt o p h oresis Syste m S afety Fe at ures 
 
T here are s e veral desi g n feat ur es of t he I P S t o e ns ure safet y:  
 
•  
 
 
 
 
 
 
 
 
•  T he ele ctr o de is h o use d c o m pletel y i nsi de t he ear pl u g, greatl y re d uci n g t he p ossi bilit y 
of b ur ns ca us e d b y direct c o ntact bet w ee n t he el ectr o de a n d s ki n.   
 
•  T he ret ur n electr o de has a lar ge s urface area, w hic h decreases c urre nt de nsit y a n d 
re d uces s ki n irritati o n p ote ntial. 
 
 
  
 
•  
 
  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 5  of 8 1  
•  
 
 
 
7. 1. 2.   I o nt o p h oresis B asic O per ati n g Pri nci ples  
S u bject Pre p ar ati o n  
 
T he ot olar y n g ol o gist will perf or m a sta n dar d ear clea ni n g t o re m o ve cer u me n t hat ma y 
affect  t he a bilit y of t he i n vesti gat or t o vis ualize t he T M or affect  t he a bilit y of t he dr u g 
s ol uti o n t o c o ntact t he T M. T he ot olar y n g ol o gist will i ns pect t he T M u n der a n o p erati n g 
micr osc o pe t o e ns ure t h ere is n o T M p erf orati o n t hat w o ul d per mit dr u g i nt o t he mi d dle 
ear, a n d t o e ns ure n o ot her c ontrai n dicati o ns relate d t o T M c o n diti o n are prese nt . N ote t hat 
a pre-st u d y t y m pa n o gra m will als o ser ve as an a d diti o nal  mec ha nis m t o eli mi nate s u bjects 
wit h a T M perf orati o n.  
 
Dr u g I nstill ati o n  
 
First, t he ot olar y n g ol o gist uses t he E arset Sizers  t o select t he a p pr o priate E arset  siz e f or 
t he ear ca n al re q uiri n g tr eat me nt. T he ot olar y n g ol o gist t he n places t he ear pl u g p orti o n of 
t he selecte d E ars et  i nt o t he ear ca n al. O nce t he ear pl u g is p ositi o ne d, t he ot olar y n g ol o gist 
ge ntl y re m o v es t he pr otecti ve li ner, e x p osi n g t he P S A t o t he ear ca nal. Usi n g t he de vice 
ha n dle, circ u mfere ntial press ure  is a p plie d t hr o u g h t he ear pl u g, a gai nst t he s urface of t he 
ear ca nal e ns uri n g a d hesi o n of t he P S A . T he ot olar y n g ol o gist t he n r o utes t he c oile d ca ble 
be hi n d t he ear a n d attac hes t he cli p t o t he patie nt’s cl ot hi n g . T h e Earset’s i nte grate d fill 
s yste m is use d t o i nstill t he selecte d dr u g i nt o t he e xter nal ear ca nal. A t y pical a d ult ear 
ca nal, i ncl u di n g t he Ears et reser v oir, will acc o m m o date a p pr o xi matel y 1 -2 cc’s of fl ui d.  
T he ot olar y n g ol o gist re p eats t he pr ocess if re q uir e d f or t he sec o n d ear a n d c o n nects t h e 
Earset/ Ears ets a n d Ret ur n Electr o de Patc h t o t he S yste m Ca ble c o n n ecte d t o t he C o ntr ol 
U nit. T he Ret ur n Electr o de Patc h is a d h ere d t o t h e patie nt’s s ki n, t y picall y o n t he bac k of 
t he nec k or t he ar m.  
 
S u bse q ue ntl y, t he C o ntr ol U nit is t ur ne d o n b y re m o vi n g t he batter y p ull ta b . I o nt o p h oresis 
is starte d b y pressi n g t he a p pr o priate yell o w  or bl ue b utt o ns o n t he C o ntr ol U nit . After a 
c urre nt ra m p -u p peri o d, a direct c urre nt of u p t o 0. 8 m A is a d mi nistere d  (sc he m atic i n 
Fi g ure 5 ). D uri n g t his ti me, t he direct c urre nt tra ns p orts t he dr u g i nt o t he t y m pa ni c 
me m bra ne  tiss ue (sc he m atic i n Fi g ure  6 ). C urre nt deli ver y is t he n c o m plet e d wit h a ra m p-
d o w n peri o d . T he e ntire c urre nt d eli ver y p eri o d lasts a p pr o xi matel y 1 0 mi n utes. T he 
C o ntr ol U nit all o ws t he user t o i nitiate, pa us e, or res u me c urre nt d eli ver y fr o m t he C o ntr ol 
U nit at a n y ti me . T h e I P S 2. 0 i ncl u des a n a d d e d ‘ Re d uce’ feat ur e t o all o w t he user t o 
o pti o nall y a n d te m p oraril y  re d uce t he c urre nt le vel b y 2 5 % if a s u bject e x perie nces 
disc o mf ort d uri n g i o nt o p h oresis. If t he Re d u ce feat ure is us e d, t he de vice trac ks o verall 
c har ge a n d acc or di n gl y a dj usts deli ver y ti me, e ns uri n g t he t otal c har ge/ d ose deli vere d is 
t he sa me as w h e n the Re d uce feat ur e is n ot use d.  D uri n g I o nt o p h oresis, t he ot olar y n g ol o gist 
ma y use t h e E arset’s  i nte grate d fill s yste m t o fill a d diti o nal dr u g i nt o t he ear ca nal, if lea k 
of s ol uti o n has occ urre d .  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 7  of 8 1  
 
Fi g ure 7 . T us k er M e dic al T y m p a n ost o m y T u be  
 
 
 
 
 
  
 
T he T D S is pr o vi de d t o t he p h ysicia n  wit h o n e pre -l oa de d T us k er Me di cal  T y m pa n ost o m y 
T u be. It is pr o vi de d sterile a n d f or si n gle -use o nl y.  Fi g ure 8  pr o vi des a gra p hic 
re pres e ntati o n of t he T D S.  
 
Fi g ure 8 . T u be Deli ver y S yste m  
 
T o use t he d e vice, t h e p h ysicia n p ositi o ns  t he bl u nt ti p of t he de vice , u n der micr osc o pic 
g ui da n ce , a gai nst t he t y m pa nic me m bra ne at t he i nte n de d m yri n g ot o m y site. U p o n 
act uati o n  of t he de vice , t he T D S perf or ms t he foll o wi n g acti o ns i n se q ue nce  i n less t ha n 
5 0 0 msec:  
 
1)  Myri n g ot o my : t he c utter e xte n ds a fi x e d dista nce ( ma xi m u m of 3 m m) t o creat e 
a n i ncisi o n i n t he t y m pa nic me m bra n e;  
2)  T T pl ace me nt acr oss t he ty m p a nic me m br a ne:  
 
 
 
 
3)  Retr acti o n:  
 
facilitati n g atra u m atic re m o val of t he T U L A T D S fr o m t he e xter nal ac o ustic 
meat us.  
 
 
  
  
 
 
 
  
  
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 2 9  of 8 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
9. 0    T U S K E R M E DI C A L  C LI NI C A L E X P E RI E N C E   
 
  
 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 0  of 8 1  
 
 
  T he I n v esti gat or’s B r oc h ure ( CI B 0 0 7 0 0 1) pr o vi des a  
c o m plete s u m mar y of t he pri or cli nical data .  
 
 
1 0. 0   S T U D Y D E SI G N  
1 0. 1.  St u d y O bjecti ve  
Pri or cli nical trial e x perie nce h as pr o vi de d preli mi nar y  safet y a n d effecti ve ness of i n-office 
t y m pa n ost o m y t u be pla ce me nt i n c hil dre n usi n g t he Tus ker Me dical  T U L A I o nt o p h oresis 
a n d T u be D eli ver y S yst e ms. T he o bjecti ve of t his st u d y is t o  e val uat e effecti ve ness a n d 
safet y of t y m p a n ost o m y t u be place me nt usi n g t he T U L A T u be Deli ver y S yste m f oll o wi n g 
l ocal a nest hesia of t he t y m pa nic me m bra ne usi n g a li d ocai ne-bas e d a nest h etic s ol uti o n a n d 
t he T U L A I o nt o p h oresis S yste m i n a wa ke, u nse date d, u nrestr ai ne d c hil dre n i n a 
p h ysicia n’s  offic e  setti n g t o s u p p ort a mar keti n g a p plicati o n.  
 
1 0. 2.  O ver all St u d y Desi g n –  P h ases a n d E nr oll me nt  
T his st u d y is a pr os pecti ve, si n gle-ar m, m ultice nter e val uati o n of safet y a n d effecti ve ness 
of i o nt o p h oresis usi n g t h e I P S a n d T D S f or T T pl ace me nt i n-office  f or c hil dre n i n dicate d 
f or t y m p a n ost o m y t u be place me nt.  
 
 
St u d y e nr oll me nt a n d pr oce d ures will occ ur i n t w o sta ges.  
 
St a ge 1  ( O R Le a d-I n C o h ort): Sta ge 1 c o nsists of t u be place m e nt pr oce d ures i n t he O R  
u n der ge n eral a n est hesia. 
 eac h i n vesti gat or will e nr oll 2 lea d-i n 
s u bjects i n t he o perati n g r o o m ( O R) u n der g oi n g t u be place m e nt usi n g t he T u be Deli ver y 
S yste m t o pla ce t h e t y m pa n ost o m y t u be(s) u n der ge n eral a n est hesia (i e, n o li d ocai ne 
i o nt o p h oresis). Sta ge 1 is c o m prise d of t he O R Lea d-I n C o h ort (u p t o 1 0 0  s u bjects; f urt her 
descri be d i n Secti o n 1 1. 2 ).   
 
St a ge 2  (I n-Office Le a d -I n C o h ort a n d Pi v ot al C o h ort): Sta ge 2 c o nsists of i n -office 
pr oce d ures usi n g b ot h t h e li d ocai ne I o nt o p h oresis S yste m a n d t he T u be Deli ver y S yste m 
f or t he i n-office t u be pl ace me nt pr oce d ure, i ncl u di n g b ot h t he Office Lea d -I n C o h ort a n d 
t he Pi v otal C o h ort. 
 
 
 
 
 
 eac h i n vesti gat or will 
e nr oll 2 lea d -i n s u bjects i n-office u n der g oi n g t u be place m e nt usi n g t h e T D S wit h l ocal 
a nest hesia facilitate d b y t he I o nt o p h oresis S yste m (u p t o 1 0 0  s u bjects i n t he Lea d-I n Office 
C o h ort ). I n vesti gat ors m a y e nr oll i nt o t he Pi v otal C o h ort f oll o wi n g c o m pleti o n of t heir 
lea d-i n pr oce d ures. T he pi v otal c o h ort will i ncl u de 2 2 2  c hil dre n (a ges 6 m o nt hs t hr o u g h  1 2  
years, i n cl usi ve) wit h e val ua ble data i n dicate d f or t y m pa n ost o m y t u be place me nt e nr olle d 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 1  of 8 1  
at u p t o  2 5  i n vesti gati o nal ce nters ( mi ni m u m of 1 5 ce nters).iii  T he pi v otal p hase will 
i ncl u de 10 2  c hil dre n a ges 5 years a n d ol der, a n d 1 2 0 c hil dre n  less t ha n 5 years of a ge wit h 
e val ua ble d ata .  
 
All pe diatric st u d y s u bjects will f oll o w t he sa me st u d y pr ot o c ol ass ess me nts , pl us cra ni al 
ner ve e x a m f or i n-offi ce s u bjects o nl y,  a n d visit sc he d ule c o nsist i n g of scree ni n g, 
pr oce d ure a n d a 3 -w ee k p ost -pr oce d ure f oll o w -u p visit.  I n a d diti o n, s u bjects will ret ur n 
f or f oll o w-u p e x a mi nati o n e ver y 6 m o nt hs f oll o wi n g t he pr oce d ure u ntil t he t u be i m pla nts 
ha ve e xtr u de d, u p t o 2 4 m o nt hs p ost -pr oce d ure. T he i n-offi c e pr oce d ure will c o nsist of 
l ocal a nesthesia of t h e t y m pa nic me m bra ne usi n g t he T U L A I o nt o p h oresis S yste m wit h 
li d ocai ne a n d e pi ne p hri n e a nest hetic  s ol uti o n. F oll o wi n g i o nt o p h oresis, a n est hesia of t he 
T M will be assesse d a n d t y m pa n ost o m y t u be place me nt wil l be c o n d u cte d i n a nest hetiz e d 
ears usi n g t h e T U L A  T u b e Deli ver y S yst e m.  O R lea d -i n pr oce d ures c o n d u cte d wit h ge n eral 
a nest hesia will c o nsist of t y m pa n ost o m y t u b e place me nt usi n g t he T u b e Deli ver y S yste m . 
 
Safet y will be assesse d t hr o u g h re p orti n g of a d ver s e e v e nts, ot osc o pic e x a mi nati o n, cra ni al 
ner ve p h ysic al e x a m, t y m pa n o metr y a n d a u di o m etr y. 
 
1 0. 3.  Desi g n of t he Pi v ot al St u d y P h ase  
T he pi v otal p hase of t he st u d y ai ms t o c o nfir m  safet y, a n d d eter mine  w het h er t he i n -offi ce 
t u be place me nt pr oce d ure ac hie ves a n acce pta ble  pr oce d ural s u cc ess rate a n d acce pt a ble 
t u be place me nt t olera bilit y.  T he pi v otal  c o h ort will c o nsist of a sa m ple of 2 2 2  c hil dre n 
i ncl u di n g 10 2  c hil dre n a ge 5  thr o u g h  1 2  years ol d , a n d 1 2 0  c hil dre n less t ha n 5 years of 
a ge. i v   
 
T he st u d y i n cl u des t w o pri mar y e n d p oi nts  eac h of w hic h m ust be s uccessf ul f or t he trial t o 
be c o nsi dere d s uccessf ul . T he first pri mar y e n d p oi nt, Pr oce d ural S uccess, is t he pr o p orti o n 
of pi v otal c o h ort s u bjects wit h T us ker M e dical t y m pa n ost o m y t u bes place d i n all i n dicate d 
ears i n an  office pr oce d ure. T he statistical test f or t he Pr oce d ural S uccess pri mar y e n d p oi nt 
is a h y p ot hesis test a gai nst a pr oced ural s uccess p erf or ma n ce g oal.  T he p erf or ma nce g o al  
f or Pr oce d ural S uccess is f urt her descri be d i n Secti o n 1 0 .3 . 1. T he sec o n d pri mar y e n d p oi nt, 
T u be Place me nt T olera bilit y , is t he mea n s u bject -re p orte d pai n sc ore f oll o wi n g T D S t u be 
place me nt usi n g t he Faces Pai n Scale -Re vise d ( F P S -R) ( pi v otal c o h ort s u bj ects  a ges 5 a n d 
ol der o nl y) . T h e statistical test f or t he T u be Place me nt T olera bilit y pri mar y e n d p oi nt is a 
h y p ot hesis test a gai nst a t u be place me nt t olera bilit y p erf or ma nce g o al. T h e p erf or ma nce 
g oal  f or T u be Place me nt T olera bilit y is f urt h er des cri be d i n see Secti o n 1 0 . 3. 1. 
 
 
 
 
 
 The test 
a gai nst t he Pr oce d ural S uccess perf or ma n ce g o al occ urs i n t w o ste ps : 
 
                                                 
iii S u bjects w h o are c o nse nte d f or t he st u d y will be c o nsi dere d e nr olle d. T hr o u g h o ut t he pr ot oc ol, e nr oll me nt n u m bers will r eflect c o nse nte d 
e nr olle d s u bjects wit h e val ua ble data.  E nr olle d s u bjec ts w h o are deter mi ne d t o be i neli gi ble (scree ni n g fail ures), a n d e nr olle d s u bjects w h o 
wit h dra w pri or t o t he st u d y pr oce d ure are n ot i ncl u de d i n t he e nr oll me nt s u bject c o u nts prese nte d herei n.  F urt her defi niti o n of s u bjects 
i ncl u de d i n t he a nal ysis sets is pr o vi de d i n Secti o n 1 3-Statistical Met h o ds.  
i v A ges 5 t hr o u g h 1 2 years is i ncl usi ve of c hil dre n reac hi n g t heir 5 t h birt h da y, b ut n ot yet r eac hi n g t heir 1 3 t h birt h da y. A ges 6 m o nt hs t hr o u g h 
< 5 years is i ncl usi ve of c hil dre n reac hi n g t heir 6 m o nt h birt h da y, b ut n ot yet reac hi n g t heir 5 t h birt h da y.  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 5  of 8 1  
 
 
 
    
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
  
  
 
  
  
 
  
 
  
 
 
 
 
 
                                                 
 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 6  of 8 1  
1 0. 4.  St u d y P o p ul ati o n  
Sta ge 1  of t h e st u d y c o nsists of t u be place me nt pr oce d ures i n t he O R u n der ge neral 
a nest hesia. 
eac h i n vesti gat or will e nr oll 2 lea d -i n s u bjects i n t h e 
o perati n g r o o m ( O R) u n d er g oi n g t u b e place me nt usi n g t he T D S ( u p t o 1 0 0  s u bjects).  
 
Sta ge 2 c o nsists of i n -office t u be place me nt pr oce d ures usi n g l ocal a nest hesia.  
 
 
 
 
 
 
 eac h i n vesti gat o r will e nr oll 2 lea d-i n s u bjects 
i n-office u n der g oi n g t u be place me nt usi n g t he T D S wit h l ocal a nest hesia facilitate d b y t h e 
I o nt o p h or esis S yste m (u p t o 1 0 0  s u bjects). I n vesti gat ors ma y e nr oll i nt o t he pi v otal c o h ort 
f oll o wi n g c o m pleti o n of t heir lea d-i n proce d ures. T he pi v otal c o h ort will i ncl u de 1 0 2 
c hil dre n a ges 5 years a n d greater pl us 1 2 0 c hil dre n less t ha n 5 years of a ge  ( 2 2 2 c hil dre n 
wit h e val ua ble dat a t otal) . 
 
1 0. 4. 1.  Defi niti o n of E nr oll me nt  
All s u bjects w h o c o nse nt f or partici pati o n i n t he st u d y are c o nsi dere d e nr olle d.  S u bjects 
w h o d o n ot me et eli gi bilit y criteria are c o nsi dere d scree n fail ures.  Secti o n 1 3 . 0 Statistical 
Met h o ds pr o vi des f urt her defi niti o n of s u bjects i ncl u de d i n t he a nal ys is sets. 
 
 
1 0. 4. 2.  St u d y C o h ort Defi niti o ns  
1 0. 4. 2. 1.  Le a d -I n O R C o h ort 
T he Lea d -I n O R C o h ort will c o nsist of all c hil dre n  w h o u n der we nt a lea d -i n pr oce d ure 
i n t he O R. T he Lea d -I n O R C o h ort safet y a n d effecti ve ness dat a will be a n al yze d a n d 
prese nte d se p aratel y.  
 
1 0. 4. 2. 2.  Le a d -I n Office C o h ort 
T he Lea d -I n Office C o h ort will c o nsist of all c hil dre n w h o u n der we nt a lea d -i n 
pr oce d ure i n-offic e . T he Lea d -I n Office C o h ort safet y a n d effecti ve n ess data  will be 
a nal yze d a n d pres e nte d s e parat el y . 
 
1 0. 4. 2. 3.  Pi v ot al  C o h ort  
T he Pi v otal  C o h ort will c o nsist of c hil dre n w h o u n der we nt a n i n -office pr oce d ure 
usi n g t he T U L A S yste m  ( n ot i ncl u di n g Lea d-I n s u bjects). T he Pi v otal  C o h ort safet y 
a n d effecti ve n ess data will be a nal yze d  a n d pres e nte d  se paratel y.  
 
1 0. 5.  Pri m ar y E n d p oi nt s 
T he re are t w o pri mar y e n d p oi nt s f or t he st u d y. T he first pri mar y efficac y e n d p oi nt  is 
Pr oce d ural S uccess,  defi ne d as:  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 7  of 8 1  
P r o ce d ur al  S uccess : Pr o p orti o n of s u bjects i n t he pi v otal c o h ort wit h s uccessf ul place me nt 
of T us ker Me di cal t y m p a n ost o m y t u be s i n all i n dicate d ears i n an  office pr oce d ure .  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
If b ot h ears of a s u bject are i n dicate d f or T T place me nt, t he pr oce d ure m ust be s uccessf ul 
i n b ot h ears f or t he pr oce d ure t o be c o u nte d as a s uccess o n a s u bject -le vel f or t he 
Pr oce d ural S uccess pri m ar y efficac y e n d p oi nt.  If eit her ear d oes n ot recei ve a t u be, t he 
pr oce d ure is n ot c o nsi d ere d a s u ccess.  If a s u bject re q uires o nl y a u nil ateral t u b e, t he 
pr oce d ure is c o nsi dere d a s uccess w he n t he i n dicate d ear has recei ve d t he t u be. T he 
pr oce d ural s uccess defi niti o n is ali g ne d wit h t he desire d cli nical o utc o me; t he c hil d has 
T us ker t u bes place d i n all i n dicate d ears w hile a v oi di n g ge neral a nest hesia a n d a n O R visit.  
T he statistical test f or t h e pi v otal c o h ort pri mar y e n d p oi nt is a  Ba yesia n  h y p ot hesis test 
a gai nst a pr oce d ural s u ccess p erf or ma nce g oal .   
 
 
T he sec o n d  pri mar y efficac y e n d p oi nt  is T u be Place me nt T olera bilit y, defi ne d as:  
 
T u be Pl ace me nt T oler a bilit y : M ea n s u bject-re p orte d pai n sc ore f oll o wi n g T D S t u be 
place me nt usi n g t he Faces Pai n Scale -Re vise d ( F P S -R) ( pi v otal c o h ort c hil dre n a ges 5 a n d 
ol der o nl y) .  
 
 
 
 
 
   
 
 
 
 
If b ot h ears of a s u bject are i n dicate d f or t y m pa n ost o m y t u be place me nt, t h e t u be place m e nt 
pai n sc ore is c ollecte d aft er t he s ec o n d ear t u b e place me nt is c o m plete d ( o ne t u be place m e nt 
pai n sc or e p er s u bject) . T he F P S -R sc ore will be c ollecte d aft er a n y m a ni p ulati o ns re q uire d 
t o place t he t u b e s o t hat t he pai n sc ore f ull y reflects t he acti vities re q uir e d t o place t he t u be. 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 8  of 8 1  
 
 
 
 
 
 
 
 
 
 
 O nl y c o m pleters, ie, s u bjects wit h F P S-R s c ores after s u ccessf ul 
t u be i nserti o n i n all i n dicate d ears, will be  i ncl u de d i n t he pri mar y a nal ysis. 
 
1 0. 6.  S afet y E n d p oi nt  
S afet y: T he occ urre nce of all a d verse e ve nts, b y s u bject. T he t otalit y of t he safet y data 
will be s u m marize d a n d prese nte d. Safet y e v e nts will be re p orte d f or all i n-office s u bjects 
i n w hic h t he li d ocai ne s ol uti o n was i ntr o d uce d i nt o t he ear, or i ntr o d ucti o n of T D S i n ear 
f or O R lea d-i n s u bjects) (see Secti o n 1 3 .2 . 3), 
 
 
 
 
 
Safet y d ata will be prese nte d se paratel y as f oll o ws:  
•  Lea d -I n O R C o h ort 
•  Lea d -I n Office C o h ort * 
•  Pi v otal C o h ort *  
 
 
 
 
1 0. 7.     Sec o n d ar y Effecti v e ness E n d p oi nts  
 
1 0. 7. 1.  T u be P ate nc y  
T u be P ate nc y :  T u be P ate nc y is t he pr o p orti o n of s u bjects i n t he pi v otal c o h ort, i n 
w hic h a T us ker Me dical t u be was s uccessf ull y pl ace d, wit h  f u ncti o nall y pat e nt t u bes i n 
all s uccessf ull y treate d ears at t he 3-wee k p ost -pr oce d ure f oll o w -u p visit.  
 
T he statistical test f or t he pi v otal c o h ort T u be P ate nc y  e n d p oi nt is a h y p ot hesis test 
a gai nst a T u be P ate n c y p erf or ma n ce g o al.  
 
1 0. 7. 2.  T u be Rete nti o n  
T u be Rete nti o n :  T u be Rete nti o n is t he pr o p orti o n of s u bjects  i n t he pi v otal c o h ort, 
i n w hic h a T us ker M e dical t u be was s u ccessf ull y place d, wit h p res e nce of a T us ker 
Me dical t u be acr oss t h e t y m pa nic me m bra n e  i n all s uccessf ull y treate d ears at t he 3 -
wee k  p ost -pr oce d ure f oll o w -u p visit . 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 3 9  of 8 1  
T he statistical test f or t h e pi v otal c o h ort T u be Rete nti o n  e n d p oi nt is a h y p ot hesis test 
a gai nst a T u be R ete nti o n p erf or ma n ce g o al.  
 
1 0. 7. 3.  A nest hesi a Effecti ve n ess  
A nest hesi a Effecti ve ness : Pr o p orti o n of s u bjects i n t he pi v otal c o h ort , w h o c o m plete d 
i o nt o p h oresis f or all i n dicate d ears, wit h a de q uate a nest hesia f or T T place me nt i n all 
treate d ears as deter mi ne d b y p h ysicia n’s e val uati o n of T M a nes t hesia pri or t o T T 
place me nt.  
 
T he statistical test f or t he pi v otal c o h ort A nest hesia Effecti ve n ess  e n d p oi nt is a 
h y p ot hesis test a gai nst a n  A nest hesia E ffecti ve n ess p erf or ma n ce g o al.  
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 
  
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 0  of 8 1  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 1  of 8 1  
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
1 0. 9.  I ncl usio n Criteri a   
1.  M ales or fe m ales at least 6 m o nt hs o l d t hr o u g h 1 2 years of a ge  at ti me of c o nse nt. viii 
 
2.  I n dic ati o n f or t y m pa n ost o m y t u be i nserti o n per Cli nical Practice G ui d eli ne (see Secti o n 
1 1 .4 . 1 Di a g n osis) 1  
 
                                                 
viii A ge 1 2 i ncl u des c hil dre n w h o ha ve n ot yet ha d t heir 1 3 t h birt h da y.  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 2  of 8 1  
3.  Be ha vi oral ca p acit y a n d c o o perati ve te m pera me nt t o u n der g o a n a wa k e pr oce d ure, 
base d o n p h ysicia n j u d g me nt  (n ot a p plic a ble t o O R Le a d -I n s u bjects) 
 
4.  S u bject’s pare nt/ g u ar dia n a n d s u bject are  willi n g  a n d a ble t o c o m pl y wit h t h e pr ot oc ol 
a n d atte n d all st u d y visits.  
 
5.  S u bject ’s pare nt/ g u ar dia n a n d s u bject are willi n g a n d a ble t o pr o vi de i nf or m e d c o ns e nt 
or asse nt as a ge a p pr o pri ate.  
 
 
1 0. 1 0.  
 E x cl usi o n Criteri a  
1.  Si g nifica n tl y atr o p hic, retracte d, bi meric, 
m o n o meric or atelect atic t y m pa nic 
me m bra ne  
 
2.  Perf orate d t y m pa ni c me m bra ne  
 
3.  Otitis e xter na  
 
4.  Acti ve or rece nt c o n diti o ns of t he t y m pa nic me m bra ne (e g, pri or m yri n g ot o m y wit h 
i nc o m plete w o u n d heali n g or re-e pit helizati o n)  
 
5.  He m ot y m pa n u m  
 
6.  Da ma ge d/ de n u d e d s ki n i n t he a u dit or y ca n al  
 
7.  Cer u me n i m pacti o n res ulti n g i n a si g nifi ca nt a m o u nt of clea ni n g re q uire d t o vis ualize 
t he t y m p a nic me m bra n e p ote ntiall y ca usi n g a brasi o n or irritati o n t o t he e xter nal ear 
ca nal  
 
8.  A nat o m y t hat precl u des s ufficie nt vis ualizati o n of a n d access t o t he t y m pa nic 
me m bra ne  
 
9.  A nat o m y t hat n ecessitates t y m pa n ost o m y t u be place me nt i n t he p osteri or h alf of t he 
t y m pa nic me m bra ne 
 
1 0.  H ist or y of se nsiti vit y or aller gic reacti o n t o li d ocai ne H Cl, tetracai ne, e pi ne p hri ne, or 
a n y h y perse nsiti vit y t o l o cal a n est hetics of t he a mi de t y pe, or a n y c o m p o n e nt*  of t he 
a nest hetic dr u g f or m ulati o n (n ot a p plic a ble t o O R Le a d -I n s u bjects) 
 
* S u bjects  wit h 
a 
k n o w n 
h y perse nsiti vit y t o 
met h yl para be n 
a n d/ or 
pr o p yl para b e n ( pres er vati ves use d i n li d ocai ne H Cl f or m ulati o ns), or t o t heir 
meta b olite para a mi n o be nz oic aci d ( P A B A), or ot her c o m p o ne nts i ncl u di n g 
p otassi u m meta bis ulfite, s o di u m meta bis ulfite, e de date dis o di u m or citric aci d.  
 
1 1.  Fa milial hist or y of i nse nsiti vit y t o li d ocai ne or ot her l ocal a n est hetics (e g, hist or y of 
i na de q uate a nest hesia wit h de ntal n u m bi n g a ge nts). (n ot a p plic a ble t o O R Le a d -I n 
s u bjects) 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 3  of 8 1  
1 2.  E lectricall y s e nsiti ve m e dical 
s u p p ort s yste ms (e g, pace ma kers, defi brillat ors , 
c oc hlear i m pla nts ) (n ot a p plic a ble t o O R Le a d -I n s u bjects) 
 
1 3.  Ot her c o n diti o ns t hat w o ul d precl u de perf or mi n g t he st u d y pr oce d ure i ncl u di n g ear 
pl u g i nc o m pati bilit y  
 
1 4.  Healt h c o n diti o ns t hat, i n t he o pi ni o n of t he i n vesti ga t or, w o ul d prese nt u n d ue ris k t o 
t he s u bject, base d o n d e vice/a nest hetic dr u g pr o d u ct la bel war ni n gs a n d preca uti o ns  
 
1 5.  S u bject is 4 years or ol d er a n d n ot a ble t o c o m plete all baseli ne assess me nts. S u bject 
is y o u n ger t ha n 4 years a n d n ot a ble t o c o m pl ete all baseli ne assess m e nts, n ot 
i ncl u di n g a u di o metr y. 
 
Ear -s pecific e x cl usi o ns ( # 1-9 , 13 ) a p pl y t o all i n dicate d ears. S u bjects ma y be i n dicate d 
f or u nilateral or bilateral t u be place me nt as des cri be d i n Secti o n 1 1 .4 . 1. If a p ote ntial 
s u bject has b ot h ears i n di cate d f or T T place me nt, b ut o ne  ear d oes n ot meet t he eli gi bilit y 
criteria, t he s u bject is n ot eli gi ble f or t he st u d y b eca use t he y w o ul d re q uire a n alter nate 
treat me nt f or t he i n eli gi ble ear. 
 
I n v esti gat ors will d oc u me nt a d diti o nal i nf or mati o n t o pr o vi de t he rati o nale f or e x cl usi o n 
f or s u bjects n ot me eti n g i ncl usi o n criteri o n 3 ( Be ha vi oral ca pacit y a n d c o o perati ve 
te mpera me nt t o u n der g o a n a wa k e pr oce d ure, bas e d o n p h ysi cia n j u d g m e nt).   
If a pre vi o usl y -det er mi ne d eli gi ble  s u bject prese nts o n t he pr oce d ure da y wit h a c ha n ge i n 
c o n diti o n , s uc h as a n ac utel y i nfecte d ear  or be ha vi or n o n -c o m plia nce , t he i n vesti gat or ma y 
us e cli nical  j u d g me nt t o deter mi ne w het her t he c o n diti o n as prese nte d precl u des perf or mi n g 
t he st u d y pr oce d ure ( E x cl usi o n 13 ). T he p h ysicia n als o has t he o pti o n t o re-sc he d ul e t he 
pr oce d ure if t he c o n diti o n is tra nsie nt. 
 
1 1. 0  S T U D Y P R O C E D U R E S  
1 1. 1.  I n vesti g at or Tr ai ni n g  
I n v esti gat ors will be as k e d t o refer t o t he dr u g p ac ka ge i nsert , d e vice I nstr u cti o ns F or Us e 
(I F U) a n d t he I n v esti gat or’s Br oc h ure f or ris ks rel ate d t o pr oce d ure, dr u g a n d de vice . T he 
I n v esti gat ors will be trai ne d o n use of t he I o nt o p h oresis a n d T u be Deli ver y S yste ms usi n g 
a m o del s yste m. 
 
1 1. 2.  Le a d -I n Pr oce d u res 
Eac h i n vesti gat or will be re q uire d t o e nr oll a n d c o n d uct  lea d-i n pr oce d ures pri or t o 
e nr olli n g s u bj ects t o t he pi v otal  c o h ort. S u bjects e nr olle d t o t he lea d -i n c o h orts m ust meet 
t he sa me eli gi bilit y criteria a n d m ust c o m plete t he sa me pr ot oc ol-re q uire d pr oce d ures a n d 
assess me nts  as t he pi v otal  c o h ort; h o we ver, t heir data will be se paratel y a nal yze d a n d 
re p orte d.  S u bjects u n der g oi n g O R pr oce d ures  usi n g ge neral a nest hesi a m ust be s uita ble 
ca n di dates f or a s ur gic al pr oce d ure u n d er ge neral a nest hesia p er I n vesti gat or’s sta n dar d 
practice.  
 
T he lea d -i n pr oce d ure criteria are s u m marize d bel o w:  
• 
2 s u bjects  a ges 6 m o nt hs t hr o u g h 1 2 years i n t he O R u n der ge n eral a nest hesi a usi n g t he 
T U L A  T D S  ( Sta ge 1), a n d  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 4  of 8 1  
• 
2 s u bjects  a ges 6 m o nt hs  thr o u g h  1 2  years  i n-office usi n g t he T U L A I o nt o p h oresis a n d  
T u be Deli ver y S yste ms  (c o n d ucte d after Sta ge 2 a p pr o val). 
 
A n y i n vesti gat or e nr olli n g pe diatri c pi v otal c o h ort i n -office pr oce d ures m ust first c o m plete 
O R lea d -i n pr oce d ures f oll o we d b y l ea d-i n i n-office pr oce d ures  f or c hil dre n. 
 
 
 
A d diti o nal o pti o nal lea d -i n s u bjects ma y b e e nr olle d at 
In v esti gat or or S p o ns or discreti o n i n a n y of t h e cate g ories liste d a b o ve.  S uc h selecti o n 
m ust occ ur pri or t o e nr oll me nt of t he s u bject i n t o t he st u d y. 
 
 
 
 
 
 
 
 
 
1 1. 4.  E v al u ati o n Met h o ds  
1 1. 4. 1.  Di a g n osis  
Eli gi ble s u bjects will be i n dicate d f or t y m p a n ost o m y t u b e place me nt  i n ali g n me nt wit h t he 
Cli nical Practice G ui deli ne .1  T he Cli nical Practice G ui deli ne  f or t y m p a n ost o m y t u bes i n 
c hil dre n was de vel o pe d b y a m ulti disci pli nar y pa nel , t o pr o vi de cli nicia ns wit h e vi de nce-
base d rec o m me n d ati o ns o n patie nt selecti o n a n d s ur gical i n dicati o ns f or a n d ma na ge me nt 
of t y m pa n ost o m y t u bes i n c hil dre n.  
 
Acc or di n g t o t he Cli nical Practice G ui deli ne, t he d ecisi o n t o perf or m u nilat eral or bilateral 
t y m pa n ost o m y t u b e i nserti o n w he n u nilateral O M E is prese nt s h o ul d be base d o n car e gi ver  
prefere nce [t o acce pt or d ecli ne t he ris k of a s ec o n d s ur gi cal pr o ce d ure] a n d t he li keli h o o d 
of persiste nt O M E de vel o pi n g i n t he o p p osite ear. F or A O M wit h pres e nce of eff usi o n, t he 
G ui deli ne rec o m me n ds bilateral T T place me nt f or u nilateral or bilat eral disease.  W it h t he 
c urre nt care p ara di g m , a p h ysici a n ma y p erf or m bilateral t u be pl ace m e nt f or a u nilateral 
c o n diti o n t o a v oi d t he ris k of m ulti ple O R pr oce d ures a n d ge n eral a nest hesia e x p os ures if 
t he sec o n d ear b ec o mes affecte d.  S i nce t his st u d y pr oce d ure is c o n d u cte d i n-office , it is 
pr o p ose d t hat t he decisi o n t o perf or m u nilateral or bilateral T T place me nt f or A O M wit h 
eff usi o n  be bas e d o n care gi v er prefere nce a n d p h ysicia n cli nical j u d gm e nt re gar di n g t he 
li keli h o o d of disease de vel o pi n g i n t he o p p osite ear, si milar t o t he 
G ui deli ne 
rec o m me n dati o n f or c hr o nic O M E.   
 
T he i n dicati o ns f or t u be place m e nt ha v e bee n clarifie d (as n ot e d i n italics) i n i nsta nces 
w here u nilateral place me nt ma y be dee me d a p pr o priate b y t h e p h ysici a n a n d acce pt a ble b y 
t he pare nt/ g uar dia n. T he c li nical i n dicati o ns f or t u be place m e nt f or c hil dre n i ncl u de:  
 
•  Bilateral T T i nserti o n f or b ilateral otitis me dia wit h eff usi o n ( O M E ) f or 3 m o nt hs or 
l o n ger (c hr o ni c O M E) a n d d oc u me nte d heari n g diffic ultie s; 
•  U nil ater al or bil ater al T T i nserti o n f or u nilateral or bilateral O M E , res p ectively, f or 3 
m o nt hs or l o n ger (c hr o ni c O M E) a n d s y m pt o ms t hat are li kel y attri b uta ble t o O M E 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 5  of 8 1  
t hat i ncl u de, b ut are n ot li mite d t o, vesti b ular pr o ble ms, p o or sc h o ol perf or ma nce, 
be ha vi oral pr o bl e ms, ear disc o mf or t, or re d u ce d q ualit y of life; 
•  U nil ater al or bil ater al  T T  i nserti o n f or rec urre nt ac ute otitis me dia ( A O M ) wit h  
u nilateral or bilateral mi d dle ear eff usi o n at t he ti me of assess me nt f or t u be ca n di dac y, 
w here rec urre nt A O M  is defi ne d as three or m ore A O M e pis o des i n t he past 6 m o nt hs 
or at least 4 A O M  e pis o des i n t he past 1 2 m o nt hs  wit h at least 1 i n t he past 6 m o nt hs . 
•  U nil ater al or bil ater al T T i nserti o n i n at -ris k c hil dre n wit h u nilateral or bil ateral 
O M E , res pectively, t hat is u nli kel y t o res ol ve q uic kl y as reflecte d b y a t y pe B (flat) 
t y m pa n o gra m or persiste nce of eff usi o n f or 3 m o nt hs or l o n ger (c hr o nic O M E). At 
ris k c hil dre n ha ve i n crease d ris k f or s peec h, la n g u a ge or lear ni n g pr o ble ms fr o m otitis 
me dia beca use of baseli ne se ns or y p h ysical, c o g niti ve or be ha vi or al fact ors.  
 
I n t his st u d y, t he care gi v er will be i nf or me d of t he ris k  of s u bse q ue nt O M E or A O M i n t he 
c o ntralateral ear a n d t he p ote ntial nee d f or a sec o n d t u be i nserti o n pr oce d ure s h o ul d t his 
occ ur.  Pri or t o pr oce d ure, t he I n vesti gat or m ust d oc u me nt w hic h ears are i nte n de d f or i n-
office t u be pl ace me nt.  
 
1 1. 4. 2.  C o nc o mit a nt Me dic ati o ns  
All pri or a n d c o nc o mita nt me dicati o ns will be rec or de d. Pri or me dicati o ns will i ncl u de all 
prescri pti o n a n d o v er -t h e-c o u nter m e dicati o ns ta ke n u p t o 2 8 da ys bef ore pr oce d ure. All 
c o nc o mita nt me dicati o ns, a n d c h a n ges t o me di cati o ns, will be rec or de d d uri n g eac h 
s u bject’s st u d y e nr oll me nt peri o d. Me dicati o ns m a y b e prescri be d b ase d o n I n v esti gat or’s 
discreti o n, e x ce pt f or dr u g s or d e vices  u n der i n vesti gati o n t hr o u g h a differe nt pr ot o c ol . 
Me dicati o ns a d mi nistere d or prescri b e d pri or t o, d uri n g or p ost -o p erati vel y  (i ncl u di n g O R 
pr oce d ures) will be d oc u me nte d  t hr o u g h st u d y e xit. 
 
1 1. 4. 3.  Cr a ni al Ner ve P h ysic al E x a m  
A  sta n dar d cra nial ner ve p h ysical e x a m will be e m pl o ye d  f or all s u bjects e nr olle d f or i n-
office pr oce d ure  at scree ni n g, after t he pr oce d ure a n d at t he 3 -wee k p ost -pr oce d ur e f oll o w-
u p visit t o i de ntif y a n y  p ote ntial a d verse effects  relate d t o t he li d ocai ne i o nt o p h oresis 
a nest hesia c o m p o n e nt of t he pr oce d ure .  
 
 
 
 A n y 
ab n or malities will be rec or de d at scree ni n g , pr oce d ure a n d at t he f oll o w -u p visit a n d t he 
s u bject will be assesse d f or a n y a d verse e ve nts. 
 
 
 
1 1. 4. 4.  Ot osc o p y  
A n ot osc o pic e x a m will be c o n d ucte d f or b ot h ears i n all s u bjects at scree ni n g, f or all ears 
i nte n de d f or treat me nt at pr oce d ure a n d f or all treat e d at t he f oll o w-u p visits.  T he  ot osc o pic 
e x a mi nati o n will be use d t o vis uall y e x a mi ne t he c o n diti o n of t he e xter nal ear ca nal a n d 
T M. R o uti ne ear cl ea ni n g m a y be c o n d u cte d o nl y t o t he e xte nt neces sar y t o e ns ure t he 
t y m pa nic 
me m bra n e a n d ear ca nal are free fr o m 
matter t hat 
ma y i nterfere 
wit h 
i o nt o p h oretic deli ver y a n d t o e ns ure vis ualizati o n of t he t y m p a nic me m bra ne. Ear clea ni n g 
at t he scree ni n g visit is re q uire d. P atie nts w h o are u nc o o perati ve d uri n g ear e x a m a n d ear 
clea ni n g at scree ni n g are n ot eli gi ble st u d y ca n di d ates .   

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 6  of 8 1  
 
T he e x a m  will be use d t o c o nfir m eli gi bilit y, t o assess t he ear ca n al a n d T M f or c ha n ges or 
a d verse effects , a n d t o i ns pect f or resi d ual dr u g pri or t o t u be place me nt . I n a d diti o n, 
a p peara nce a n d pat e nc y of t he t y m pa n ost o m y t u be a n d a p p eara nce of t he m yri n g ot o m y 
w o u n d will be e val uate d p ost -pr oce d ure a n d at t he p ost -pr oce d ure f oll o w-u p visit s. 
Prese nce or a bse n ce of m i d dle ear eff usi o n will be as sesse d. 
 
T he s cree ni n g ot osc o pic e x a m ma y be c o n d uct e d u p t o 2 8 da ys pri or t o pr oce d ure. 
Ot osc o pic e x a mi nati o n is c o nsi dere d sta n dar d of care f or t his patie nt p o p ulati o n a n d ma y 
be o btai ne d pri or t o st u d y i nf or me d c o nse nt as a s cree ni n g ass ess me nt wit hi n 2 8 da ys pri or 
t o pr oce d ure. 
 
1 1. 4. 5.  T y m p a n o metr y  
Sta n dar d t y m pa n o metr y  of b ot h ears will be e m pl o ye d t o assess T M f u ncti o n at scree ni n g 
( wit hi n 2 8 da ys  pri or t o pr oce d ure) a n d at all f oll o w-u p visit s f or all treate d ears. 
T y m pa n o metr y d ata rec or de d will i ncl u de t y m p a n o gra m t y pe, ear ca nal v ol u me, pea k 
press ure , a n d static ac o ustic i mm itta nce as a n o bjecti ve meas ure of t u be pate nc y a n d mi d dle 
ear stat us .  If a d e q uate t y m pa n o meter seal or a v ali d t y m p a n o gra m ca n n ot be ac hie ve d f or 
scree ni n g t y m p a n o metr y e val uati o n, t he s u bj ect will be c o nsi dere d a scree ni n g fail ure, a n d 
will n ot be eli gi ble f or t he st u d y.  T y m pa n o metr y is c o nsi dere d sta n dar d of care f or t his 
patie nt p o p ulati o n a n d ma y b e o btai ne d pri or t o st u d y i nf or me d c o ns e nt as a s cree ni n g 
assess me nt wit hi n 2 8 da ys pri or t o pr oce d ure.  
 
 
1 1. 4. 6.  A u di o met r y  
A u di o metr y will be e m pl o ye d  t o e val u ate heari n g stat us i n eac h ear at scree ni n g ( wit hi n 2 8 
da ys  pri or t o pr oce d ure)  a n d at t he 3 -wee k p ost -pr oce d ure f oll o w -u p visit  f or all s u bjects 
a ge 4 years or ol der . T hres h ol d testi n g will be c o n d ucte d usi n g air c o n d u cti o n a n d b o ne 
c o n d ucti o n at a mi ni m u m of 5 0 0, 1 0 0 0, 2 0 0 0  a n d 4 0 0 0 Hz , a n d air c o n d ucti o n o nl y at 
8 0 0 0 Hz . St u d y sites will ma ke eff orts t o meas ure heari n g t hres h ol ds at all 5 fre q ue n cies. 
F or y o u n ger s u bje cts (less t ha n 4 years of a ge), cli nical st u d y sites will att e m pt t o c ollect 
a u di o metr y at scree ni n g at a mi ni m u m of t w o fre q ue ncies f or b ot h air c o n d u cti o n ( A C) a n d 
b o ne c o n d ucti o n  ( B C). T he cli nical st u d y sit e a u di ol o gist will deter mi ne t he m ost 
a p pr o priate test 
met h o d  f or eac h s u bject (vis ual rei nf orce m e nt a u di o metr y ( V R A), 
c o n diti o ne d pla y a u di o metr y ( C P A)  or c o n ve nti o nal  a u di o metr y). T he met h o d use d at 
scree ni n g will be use d f or all f oll o w -u p assess me nts.  
 
A u di o metr y is c o nsi dere d sta n dar d of care f or  t his patie nt p o p ulati o n a n d ma y be o bt ai ne d 
pri or t o st u d y i nf or me d c o nse nt as a scree ni n g assess me nt wit hi n 2 8 da ys pri or t o 
pr oce d ure.  
 
1 1. 4. 7.  A nest hesi a Effecti ve n ess  
F oll o wi n g i o nt o p h oresis, t he I n vesti gat or will use p h ysicia n j u d g me nt t o assess  w het her 
t he T M is a de q uatel y a n est hetiz e d f or t he t y m p a n ost o m y t u be place me nt pr oce d ure b y  
e val uati n g s u bject res p o nse t o a ge ntle ta p of t h e T M wit h a d ull ot ol o gic i nstr u me nt , 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 4 7  of 8 1  
 T he ta p will o cc ur o n t he a nteri or h alf of t he T M at t he l o cati o n w here t he 
t y m pa n ost o m y t u be will be place d.  T his ta p assess me nt met h o d has bee n u se d s uccessf ull y 
i n pri or st u dies t o deter mi ne a de q uat e a nest hesia f or s u bse q ue nt t y m pa n ost o m y t u be 
place me nt f or b ot h c hil dre n a n d a d ults.  
 
1 1. 4. 8.  T oler a bilit y  ( F P S-R)  
T he Faces Pai n Scale -Re vise d ( F P S -R)  (Fi g u re 1 0 ) is an i nstr u me nt f or assessi n g 
pr oce d ural pai n vali date d f or use i n c hil dre n 4 years of a ge  a n d ol der. T his st u d y will 
e m pl o y t he F P S -R f or c hil dre n i n t he ol der c o h ort o nl y (a ge 5 years a n d greater). S u bjects 
a ges 5  years a n d ol der  will rate t heir disc o mf ort  f oll o wi n g T D S t u be pl ace me nt (aft er 
sec o n d ear, if bilateral tr eat me nt) usi n g t he F P S -R . If o pti o nal s u cti o n is perf or me d, t he 
s u bject will rate t heir dis c o mf ort f oll o wi n g s u cti o n of b ot h ears (if i n dicate d bilaterall y) . I n 
a d diti o n, a n F P S -R sc ore will be  c ollect e d fr o m t he c hil dre n a p pr o xi matel y 5  mi n utes after 
c o m pleti o n of t u be place me nt, or after c o m pleti o n of s ucti o n ( w hic he ver i nter ve nti o n is 
last).  A b aseli ne me as ure of ear disc o mf ort will be assesse d after ear clea ni n g  (if re q uire d) 
a n d pri or t o  E ars et place me nt.  
 
 
 
Fi g ure 1 0 . F aces P ai n Sc ale -Re vise d  
 
If a s u bject disc o nti n ues t he pr oce d ure pri or t o c o m pleti o n of t u be place me nt, a n F P S-R 
sc ore will be c ollecte d f or t he disc o nti n ue d pr oce d ure. 
 
1 1. 4. 9.  T oler a bilit y ( F L A C C ) 
T he F L A C C ( Face, Le gs, Acti vit y, Cr y, C o ns ola bilit y) s cale is a met h o d t o e val u ate 
be ha vi oral distress  f or c hil dre n as y o u n g as  2 m o nt hs or i n di vi d uals t hat are u na ble t o 
c o m m u nicate t heir pai n. 6 1 T he F L A C C is a vali d a n d relia ble pe diatri c o bser vati o nal 
me as ure t h at ra n ges fr o m l o w ( 0) t o hi g h ( 1 0) distress. T he F L A C C is rec o m me n de d i n t he 
Pe dI M M P A C T c o nse ns us state me nt a n d is a wi del y use d o bs er vati o nal meas ure of 
pe diatric be h a vi oral pai n a n d distress .6 2 
 
T he scale has fi ve cat e g ories w hic h are eac h assi g n e d a sc ore of 0, 1 or 2 b y a n e val u at or, 
as s h o w n i n T a ble 3 . 
 
 
 
 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 5 0  of 8 1  
 
 
 
1 1. 6.  Scree ni n g E v al u ati o ns  
After writte n i nf or me d c o nse nt is o btai ne d, t he s u bject is c o nsi dere d e nr olle d i n t he st u d y 
a n d will be scree ne d f or i ncl usi o n a n d e x cl usi o n criteria .  
  
Scree ni n g e val uati o ns m a y be c o n d ucte d o n d a y of pr oce d ure or at a se parate visit u p t o 2 8  
da ys  pri or t o pr oce d ure. T he Scree ni n g E v al uati o ns i ncl u de  (i n a n y or der): 
 
1.  Me dical hist or y a n d c o n c o mita nt/ pri or me dicati o ns  
 
2.  Cra nial ner ve p h ysi cal e x a m  (i n-office pr oce d ure s u bjects o nl y)  
 
3.  Micr osc o pic ot osc o p y  wit h ear clea ni n g  
 
4.  T y m pa n o metr y  a n d A u di o metr y (i n eit her or d er)  
 
5.  I n cl usi o n/ E x cl usi o n 
 
1 1. 7.  Pr oce d ure  
1 1. 7. 1.  Ot osc o pic E x a mi n ati o n a n d E a r Pre p a r ati o n  
A n ot osc o pic e x a m will be c o n d ucte d usi n g a micr osc o pe f or b ot h ears i n all s u bjects pri or 
t o pr oce d ure.  T he ot osc o pic e x a mi nati o n will be use d t o vis uall y e x a mi ne t he c o n diti o n of 
t he e xter nal ear ca nal a n d T M. R o uti ne ear cl ea ni n g m a y be c o n d uct e d, if n ee de d, o nl y t o 
t he e xte nt necess ar y t o e ns ure t he t y m pa ni c me m bra ne a n d ear ca n al are free fr o m matter 
t hat ma y i nterfere wit h or i nfl ue nce t he e val uati o n a n d t o e ns ure vis ualizati o n of t he 
t y m pa nic me m bra ne. C h a n ges i n c o nc o mita nt me dicati o ns will be rec o r de d. 
 
1 1. 7. 2.  E arset Sizi n g  
T he I P S Earset  is a vaila bl e i n 6  sizes. T he ear sizi n g pr oce d ure will be perf or me d acc or di n g 
t o t he I nstr ucti o ns f or Us e (I F U) pr o vi de d wit h t h e I P S. If t he s u bject’s ear is n ot c o m pati ble 
wit h t h e ear pl u g a n d fit ca n n ot be esta blis he d t o e ns ure t he ear pl u g ca n pr o perl y seal i n t he 
ear ca nal, t he s u bject will be c o nsi dere d a scree n i n g failure . 
 
1 1. 7. 3.  A nest hetic S ol uti o n P re p ar ati o n  
T he  2 % li d ocai n e/ 1: 1 0 0, 0 0 0 e pi ne p hri ne a nest h etic s ol uti o n will be war me d t o b o d y 
te m perat ur e pri or t o i nstillati o n  of a p pr o xi matel y 1 -2 m L  i nt o eac h ear ca n al t o mi ni mize 
t he cal oric effect.  
 
1 1. 7. 4.  E arset  Pl a ce me nt a n d Dr u g I nstill ati o n  
Baseli ne t olera bilit y will be assesse d bef ore place me nt of t he Earset. T he Earset ear pl u g 
of t he siz e deter mi ne d i n t he ear sizi n g pr oce d ure is t he n place d i nt o t he ear ca n al . O nce 
t he ear pl u g is p ositi o ne d, t he pr otecti ve li ner is re m o ve d, e x p osi n g t he P S A t o t he ear ca n al. 

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Circ u mfere ntial press ure is a p plie d t hr o u g h t he ear pl u g a gai nst t he s urface  of t he ear ca n al,  
e ns uri n g a d hesi o n of t he P S A. T he Earset’s i nte grate d fill s yste m is use d t o i nstill t he 
selecte d dr u g i nt o t he ear ca nal. T his pr ocess is re peate d  f or t he sec o n d ear.  
 
T he  Electr o de  Ca ble is s na ppe d  t o t he Ret ur n Electr o de Patc h. T he E lectr o de Ca ble 
c o n nects t he E arsets  a n d t he C o ntr ol U nit. T he Ret ur n Electr o de Pat c h is  t he n attac h e d t o 
t he patie nt at a clea n, dr y site (s uc h as t h e s h o ul der near t he bas e of t he nec k) t hat is clear 
of lesi o ns, b o n y pr ot u bera nces a n d e x cessi ve hair. Pri or t o placi n g t he ret ur n electr o de o n 
t he patie nt, t he i n vesti gat or will assess t he l ocati o n f or pre-e xisti n g er yt h e m a usi n g t he fi ve 
p oi nt Draiz e er yt h e ma s c ore w h ere 0 i n dicates n o er y t h e ma, 1 = ver y sli g ht er yt he ma 
( barel y p erce pti ble), 2 = well-defi ne d er yt he ma, 3 = m o derate t o se v ere er yt he ma  , 4 = se v ere 
er yt h e ma t o sli g ht esc h ar f or mati o n. 6 5 Cate g or y 4  als o i ncl u de s visi ble blister or b ur n. T he 
l ocati o n will be assesse d a gai n f oll o wi ng i o nt o p h oresis.  
 
I n t he e ve nt t hat dr u g has bee n i ntr o d uce d i nt o t he ear a n d i o nt o p h oresis was n ot i nitiate d,  
t he s u bject will ret ur n f or a f oll o w-u p visit 2 t o 5 da ys p ost pr oce d ure t o c o m plete all 
assess me nts re q uire d  at t he 3 -wee k visit si nce dr u g wil l ha ve bee n i ntr o d uce d i nt o t he ear. 
T his s u bject is i ncl u de d i n t he Safet y A nal ysis Set, b ut is n ot c o nsi dere d a disc o nti n ue d 
pr oce d ure si nce i o nt o p h oresis was n ot i nitiate d a n d is t heref ore n ot i ncl u de d i n t he F ull 
A nal ysis Set. T h e s u bject ma y t he n b e e xite d fr o m t he st u d y aft er t he f oll o w -u p visit if n o 
u nres ol ve d de vi ce, pr oce d ure or dr u g -relate d a d verse e ve nts are prese nt.  If t here are 
u nres ol ve d a d v erse e ve nts, t he s u bject m ust als o ret ur n f or t he sc h e d ule d 3-wee k f oll o w -
u p visit.  H o we ver, if t he s u bject pla ns t o u n der g o t u be place me nt i n t he O R , t he s u bject’s 
s u bse q ue nt pr oce d ure s u ccess will be d o c u me nte d as d escri be d i n Secti o ns 1 0. 8. 5 a n d 
1 1. 7. 1 0 . T his s u bse q ue nt pr oce d ure m ust ta ke place wit hi n 2 m o nt hs of t he st u d y pr oce d ure. 
N o a d diti o nal f oll o w -u p is re q uire d f oll o wi n g t his n o n -st u d y t u be place me nt pr oce d ure. 
 
1 1. 7. 5.  St art of I o nt o p h oresis  
T o be gi n a n est hesia, t he C o ntr ol U nit b utt o ns are presse d t o i nitiate c urre nt. I nitiati o n of 
c urre nt re pres e nts t he be gi n ni n g of t he i o nt o p h oresis pr oce d ure. T h ere are t w o b utt o ns, o ne 
f or eac h ear. Wit h o ut i nterr u pti o ns, t he C o ntr ol U nit o perati o n will ta ke a p pr o xi matel y 1 0 
mi n utes . Pr o gress t hr o u g h t he i o nt o p h oresis c ycle ca n be m o nit ore d via t h e pr o gres s b ars 
o n t he C o ntr ol U nit w hic h fill t o i n dicate pr o gress t o war d c o m pleti o n.  
 
T he pr oce d ure ca n be p a use d at a n y ti me, a n d t he n res u me d. T he C o ntr ol U nit will acc o u nt 
f or t hese p a uses t o e ns ure c o nsiste nt c urre nt d ose d eli ver y, a n d will pr o vi de a visi ble si g nal 
w he n c o m plete. T he I P S 2. 0 als o i ncl u des a  ‘ Re d uce’ feat ure t o all o w t he user t o o pti o nall y 
a n d te m p oraril y re d u ce t he c urre nt le vel b y 2 5 % if a s u bject e x perie nces disc o mf ort d uri n g 
i o nt o p h oresis. If t h e Re d uce feat ur e is us e d b y t he o perat or, t he d e vice trac ks o verall 
c har ge, e ns uri n g t otal n o mi nal c har ge/ d ose is deli vere d. 
 
 
 
 
 
 
 
 
 

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1 1. 7. 6.  A nest hetic S ol uti o n a n d Ret ur n Electr o de P atc h Re m o v al  
At t he e n d of i o nt o p h oresis, t he Earset(s) , a n d Ret ur n Electr o de  Patc h are re m o ve d a n d t he 
a nest hetic s ol uti o n is re m o ve d fr o m t he ear ca nal eit her b y wic k o r hea d  tilti n g. T he 
I n v esti gat or will i ns pect t he ear ca n al a n d T M usi n g a n o perati n g  micr osc o pe t o directl y 
vis ualize t he a nat o m y c o nfir m re m o val of  resi d ual dr u g i n t he ear ca nal.  
 
T he ret ur n ele ctr o de l ocati o n 
will be assess e d f or er yt he m a u p o n c o m pleti o n of 
i o nt o p h oresis a n d re m o v al of t h e ret ur n electr o d e patc h. O bs er vati o ns will be gra de d usi n g 
t he fi ve p oi nt Draiz e er yt he ma sc ore w here 0 i n dicates n o er yt he ma, 1 = ver y sli g ht 
er yt h e ma ( barel y p erce pti ble), 2 = well -defi ne d er yt he ma, 3 = m o dera te t o se vere er yt he m a, 
4 = se vere er yt h e ma t o sli g ht es c har f or mati o n. 6 7 Cate g or y 4 als o i ncl u des visi ble blister or 
b ur n. Sc ores of 3 or greater will be c o nsi dere d a d v erse e v e nts.  
 
 
1 1. 7. 7.  P ost -I o nt o p h oresis A nest hesi a Effecti v e ness 
F oll o wi n g i o nt o p h oresis, t he I n v esti gat or will i ns pect t he ear ca nal a n d T M usi n g t he 
micr osc o pe. T he I n vesti gat or will t he n li g htl y ta p o n t he a nteri or half of t he T M (at t he 
l ocati o n w here t he t y m p a n ost o m y t u b e will  be pl ace d) t o e val uate s u bject se nsati o n a n d 
w het her a nest hesi a is a de q uate f or t y m p a n ost o m y t u b e place me nt. P ai n res ulti n g fr o m 
i na de q uate a nest hesia aft er T M t a p as j u d ge d b y t h e s ur ge o n will be rec or de d as a n a d verse 
e ve nt reflecti n g a n u nacce ptable le vel of s u bject disc o mf ort t hat pre ve nts t h e s ur ge o n fr o m 
atte m pti n g t o i nsert t h e t u be . 
 
 
 
 
 
 
 
 
 
 
 
1 1. 7. 8.  T y m p a n ost o m y T u be Pl ace me nt  
T he I n vesti gat or will place t h e T T usi n g t h e T D S w hile t he s u bject’s hea d is ge ntl y 
sta bilize d b y t he cli nic staff, as is t y pical f or sta n d ar d of care ear e x a mi nati o ns. 
 
 
 
 
 
 
 
 
 
 
F oll o wi n g T D S t u be pl ace me nt, t he s u bject will re p ort t heir p ost -t u be place me nt ear 
disc o mf ort ( o n a b y-s u bj ect basis) usi n g t he F P S -R .   

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T he i n vesti gat or ma y ele ct t o use s ucti o n o nl y aft er place m e nt of T T i n all i n dicat e d ears. 
A l o w le vel of s ucti o n ma y b e use d t o ge ntl y re m o ve fl ui d t hr o u g h t he place d t u be, ta ki n g 
care t o n ot disl o d ge t he t u be. Use of s ucti o n will be rec or de d.  F oll o wi n g s ucti o n, t he 
s u bject will re p ort t heir p ost-s ucti o n ear disc o mf ort ( o n a b y-s u bject basis) usi n g t he F P S-
R.   
 
P ost -o perati ve care , i ncl u di n g otic dr o ps, will be prescri be d p er i n vesti gat or’s discreti o n. 
All p ost -o perati ve me dicati o ns will be d oc u me nte d.  
 
If a n u n e x pecte d seri o us c o m plicati o n occ urs d uri n g t he pr oce d ure , t he pr oce d ure will be 
ter mi nate d. The I n vesti gat or will ta ke all a p pr o priate i ntra - a n d p ost -treat me nt meas ures t o 
e ns ure s u bject safet y a n d pr o per tr eat me nt . T h e I n v esti gat or will n otif y T us k er Me dical  a n d 
t heir I R B i m me diatel y, b ut i n n o i nsta nces greater t ha n 2 4 h o urs  of t he i nci de nt .  
 
1 1. 7. 9.  P ost -Pr oce d ure Ot osc o p y a n d Cr a ni al Ner v e E x a m  
A n ot osc o pic e x a m will be c o n d ucte d p ost -pr oce d ure .  T he ot osc o pic e x a mi nati o n will be 
use d t o vis uall y e x a mi ne t he c o n di ti o n of t he e xter nal ear ca nal, T M a n d t u be. A cra nial 
ner ve p h ysic al e x a m will als o be c o n d ucte d  pre - a n d p ost -pr oce d ure  f or all i n-office 
s u bjects.   
 
1 1. 7. 1 0.  
U ns uccessf ul Pr o ce d u r es 
 
If t he i n-offi ce pr oce d ure  is n ot a s uccess a n d t he p h ysicia n refers t he s u bject f or tra diti o nal 
O R T T pla ce me nt, t h e I n vesti gat or will d oc u me nt t he O R pr oce d ure T T place me nt s u ccess.  
Reas o ns f or a n y O R pr oce d ural fail ures ( of T T place me nt) will be d oc u me nte d.  T he O R 
pr oce d ure m ust  ta ke place wit hi n 2  m o nt hs of t he first i n -office pr oce d ure. T he s u bject 
m ust c o m plete a p ost -pr oce d ure f oll o w -u p visit after t he faile d i n-office pr oce d ure , at t he 
pr ot oc ol s pecifie d 3 -wee k f oll o w -u p visit, or earlier if t he O R pr oce d ure is pla n ne d pri or  t o 
t he 3-wee k visit . If n o T us ker t u be was place d, no  a d diti o nal f oll o w-u p visit is re q uire d 
f oll o wi n g t he s u bse q ue nt pr oce d ure.  If a T us ker t u be was place d, t he s u bject s h o ul d f oll o w 
t he pr ot oc ol-s pecifie d f oll o w-u p visit sc he d ule t o assess safet y of t he  T us k er t u be.  
 
 
 
 
 
  
 
 
 
  
  
 
 
  
 
  
 
  
 
 
 
 
    

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1 1. 9.  3 -Wee k P ost -Pr oce d u re F oll o w -U p Visit ( +/ - 7 D a ys)  
 
1.  All s u bjects are re q uire d t o ret ur n f or t he 3 -wee k  p ost -pr oce d ure f oll o w -u p visit.  
 
2.  A n  ot osc o pic e x a mi nati o n will be use d t o vis uall y e x a mi ne t he c o n diti o n of t he e xter nal 
ear ca nal , T M, m yri n g ot o m y, t u be rete nti o n a n d pate nc y.  
 
3.  T he s u bject wil l c o m pl ete t he a u di o metry  a n d t y m pa n o metr y, a n d cra nial ner ve 
p h ysical e x a m  (f or i n-office s u bjects o nl y) . 
 
4.  S u bjects  will be e val uate d f or a n y a d v erse e v e nts , a n d c han ges i n c o nc o mita nt 
me dicati o ns will be rec or d e d. 
 
 
1 1. 1 0.  
6, 1 2, 1 8 a n d 2 4 -m o nt h P ost -Pr o ce d ure F oll o w -U p 
Visits ( +/ - 2 8 d a ys)  
 
1.  All s u bjects are re q uire d t o ret ur n f or a d diti o nal f oll o w -u p visits t hr o u g h c o nfir mati o n 
of t u be e xtr usi o n ( b ot h ears if bilateral t u be place me nt).  
 
2.  A n ot osc o pic e x a mi nati o n will be use d t o vis uall y e x a mi ne t he c o n diti o n of t he e xter nal 
ear ca nal, T M , m yri n g ot o m y, t u be rete nti o n a n d pate nc y.  
 
3.  T he s u bject will c o m plete t y m pa n o metr y . If a u di o metr y is i n dicate d, t he st u d y will 
c ollect a u di o metric d ata h o we ver t h ere is  n o st u d y re q uire me nt f or a u di o metr y or 
a u di o metr y m et h o d f or f oll o w -u p visits s u bse q ue nt t o t he 3 -wee k visit.  
 
4.  S u bjects  will be e val uate d f or a n y a d v erse e v e nts , a n d c ha n ges i n c o nc o mita nt 
me dicati o ns will be rec or de d.  
 
5.  T he s u bject will be e xite d fr o m t he st u d y foll o wi n g c o nfir mati o n of t u be e xtr usi o n or 
c o m pleti o n of  t he 2 4 m o nt h visit if t u be re mai ns i n place.  
 
1 1. 1 1.  
 S u m m ar y –  St u d y Fl o w a n d St u d y E v al u ati o n s 
T he fl o w of s u bject parti ci pati o n, visits a n d e val uati o ns is de p icte d as a sc he matic i n 
Fi g ure 1 1 . 

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Fi g ure 1 1 . Sc he m atic of St u d y Desi g n Fl o w  
 
 
T he sc he d ule of e val u ati o ns f or eac h st u d y visit is prese nte d i n T a ble 4 . 
 
 
 
 
 
 
 
 
 

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All re p orte d or o bser ve d a d verse e v e nts t hat occ ur d uri n g or after t he pr oce d ure will be 
rec or de d. T he st u d y I n v esti gat or will deter mi ne w het her a n a d verse e v e nt has occ urre d, 
w het her life-t hr eate ni n g, seri o us or n o n-seri o us. Pre-e xisti n g c o n diti o ns s h o ul d n ot be 
re p orte d as a d vers e e ve nts u nless t here has bee n a w orse ni n g i n t he se verit y or fre q ue n c y, 
w h ic h ca n n ot b e attri b ute d t o nat ural hist or y or pr o gressi o n of t he dis ease. T his defi niti o n 
d oes n ot de pe n d o n t he ca usal relati o ns hi p wit h t he de vice , dr u g or pr ot oc ol re q uire me nts.  
 
A n y c ha n ge of cli nic al si g nifica nce , i ncl u di n g v erti g o, na usea a n d v o mitin g,  d eri ve d fr o m 
t he pr ot oc ol e val uati o ns i ncl u di n g o bser vati o ns a n d patie nt-re p orte d fi n di n gs will be 
i ncl u de d as a d vers e e ve nts. A d verse e ve nts will als o i ncl u de o p erati ve a n d rec o v er y 
o bser vati o n f or l ea d -i n pr oce d ures c o n d ucte d i n t he O R wit h ge neral an est hesia i ncl u di n g, 
b ut n ot li mite d t o, cli nicall y -m ea ni n gf ul vital si g n c h a n ges, e mer ge n ce deliri u m, p ost -
o perati ve na usea, v o miti n g, dis orie ntati o n, a n d c o m plicati o ns relate d t o i nt u bati o n or 
i n d ucti o n. 
 
All A d vers e E ve nts ( A Es) will be rec or de d o n de dicate d A E  case re p ort f or ms . T he e ve nt, 
date of o nset, s e verit y, s eri o us ness, d urati o n, treat me nt, o utc o me , dat e or res ol uti o n a n d 
relati o ns hi p t o de vice, pr oce d ure or dr u g will be rec or de d o n t h e A E  case re p ort f or m 
(C R F ). A Es will be cate g orize d b y s eri o us ness, relate d ness t o pr oce d ure, i n vesti gati o nal 
dr u g, or d e vice w het h er a ntici pate d or u na ntici pate d . All a d verse e ve nts will be c o de d usi n g 
sta n dar d ter ms.  
 
1 2. 2.  Seri o us A d verse E ve nts  
If a n u ne x pecte d seri o us c o m plicati o n res ulti n g in a n a d verse e ve nt occ urs d uri n g t he 
pr oce d ure, t he  pr oce d ure will be ter mi nate d . T he I n vesti gat or will ta ke all a p pr o priate i ntra - 
a n d p ost -pr oce d ural meas ures t o e ns ure s u bject safet y a n d pr o per treat me nt. I n t he e ve nt of 
a seri o us a d verse e v e nt  at a n y t i me d uri n g t he st u d y, t he I n v esti gat or will n otif y t he S p o ns or 
a n d t heir I R B i m me diatel y or n o lat er t ha n wit hi n 2 4 h o urs.  
 
All Seri o us A d vers e E v e nts  t hat ha ve n ot res ol v e d b y t he e n d of t he s u bject's p artici pati o n 
i n t he st u d y m ust be f oll o we d u ntil t he e v e nt res ol ves, i m pr o ves, or sta bilizes. T he 
i n vesti gat or s h o ul d r e p ort a n y f oll o w-u p i nf or mati o n as it bec o mes a v aila ble.  
 
1 2. 3.  A d verse E ve nt Defi niti o ns   
A dverse Eve nt ( A E)  
A n A E  is a n y u nfa v ora bl e a n d u ni nte n de d si g n, s y m pt o m, or disease te m p orall y ass o ciate d 
wit h t he pr oce d ure or use of t he de vice or i n vesti gati o nal dr u g, a n d d oes n ot i m pl y j u d g me nt 
a b o ut ca usalit y.  
 
Seri o us A dverse Eve nt ( S A E)  
A Es  are classifie d as s eri o us or n o n -seri o us. A seri o us a d verse e ve nt is a n y A E t hat i s: 
 
•  Fatal  
 
•  Lif e -t hreate ni n g 
 
•  Re q uires or pr ol o n gs h os pital sta y  
 

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•  Res ults i n persiste nt or si g nifica nt i nca pacit y  or s u bsta ntial disr u pti o n of t he a bilit y t o 
c o n d uct n or mal life f u ncti o ns  
 
•  Le d t o fetal distress, f etal deat h or c o n ge nital a b n or malit y or birt h defect  
 
•  A n i m p orta nt me dical e ve nt t hat ma y j e o par dize t he s u bject, a n d ma y re q uire me dical 
or s ur gical i nter ve nti o n t o pre ve nt o ne of t he ot her seri o us o utc o mes n ote d a b o ve .  
 
Life T hre ate ni n g A dverse Eve nt or Life -T hre ate ni n g S us pecte d A dverse Re acti o n  
A n a d verse e v e nt or s us pecte d a d verse reacti o n  is c o nsi dere d life t hreate ni n g if, i n t he vie w 
of eit her t he i n v esti gat or or s p o ns or, its o cc urre n ce places t he s u bject at i m me diate ris k of 
deat h. It d oes n ot i ncl u d e a n a d v erse e ve nt t hat, ha d it occ urre d i n a m or e se vere f or m, 
mi g ht ha ve ca use d d eat h.  
 
U n a ntici p at e d A dverse Devic e Effect ( U A D E)  
A  U A D E  is a n y seri o us a d verse effect o n healt h or safet y or a n y life -t hreate ni n g pr o ble m 
or deat h ca use d b y, or ass ociate d wit h, a de vice, if t hat effect, pr o ble m or deat h was n ot 
pre vi o usl y i de ntifie d i n n at ure, se verit y, or de gree of i nci de nce i n t he i n vesti gati o nal pla n 
or a p plicati o n, or a n y ot her u na ntici pate d seri o us pr o ble m ass ociate d wit h a de vice t hat 
relates t o t he ri g hts, safet y, or welfare of s u bj ects.  
 
I n or der t o e ns ur e s u bject safet y d uri n g t he st u d y, all a d verse e v e nts assess e d as “seri o us ” 
i n t he o pi ni o n of t he I n v esti gat or will be re vie we d b y t h e Me dical M o nit or t o deter mi n e 
a n y ca usal relati o ns hi p t o t he st u d y dr u g, de vi ce  or pr oce d ure. All a d verse e v e nts t hat d o 
n ot meet a n y of t he criteria f or seri o us s h o ul d b e re gar de d as n o n -seri o us a d verse e ve nts. 
N o n -seri o us a d v erse e ve nts m ust still be d oc u me nte d o n t he a p pr o pri ate C R F.  
 
Re p orti n g  
T he s p o ns or will n otif y F D A , all re vie wi n g I R Bs a n d all partici pati n g I n vesti gat ors of 
p ote ntial seri o us ris ks, fr o m t his st u d y or a n y ot h er s o urce, as s o o n as p ossi ble,  b ut i n n o 
case later t ha n 1 5 cale n d ar da ys after t he S p o ns or deter mi nes t hat t he i nf or mati o n q ualifies 
f or re p orti n g, i ncl u di n g: 
 
1.  S us pecte d a d verse dr u g reacti o ns t hat are c o nsi dere d b ot h seri o us a n d u ne x pecte d,  
 
2.  F i n di n gs fr o m ot her st u dies t hat s u g gest a si g nifi ca nt ris k i n h u ma ns e x p ose d t o t he 
dr u g,  
 
3.  F i n di n gs fr o m a ni mal or i n vitr o testi n g t hat s u g gest a si g nifi ca nt ris k i n h u ma ns 
e x p ose d t o t he dr u g, a n d  
 
4.  A n i ncreas e d rat e of occ urre nce of seri o us s us pect e d a d verse reacti o ns.  
 
I n a d diti o n, t he s p o ns or will n otif y  F D A , all re vie wi n g I R Bs a n d partici pati n g i n v esti gat ors 
wi t hi n 1 0 w or ki n g d a ys after t he Sp o ns or first recei ves n otice of a n U na ntici pate d A d verse 
De vice Effect .  
 
He alt h C a n a d a Re p orti n g  
 
I n v esti gatio nal Dr u g A E Re p orti n g:  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 5 9  of 8 1  
  
T he s p o ns or will n otif y Healt h Ca na da or a n y seri o us u ne x pecte d a d verse dr u g reacti o n  
•  W here it is neit her fatal n or life -t hreate ni n g, wit hi n 1 5 da ys after bec o mi n g a ware 
of t he i nf or mati o n;  
•  W here it is fatal or life -t hreate ni n g, wit hi n 7 da ys after bec o mi n g a ware of t he 
i nf or mati o n.  
 
I n v esti gati o nal De vic e A E Re p orti n g: 
 
T he s p o ns or will n otif y Healt h Ca na d a of a n y i nci de nt i n v ol vi n g t he i n vesti gati o nal d e vice 
t hat: 
•  Is rel ate d t o a fail ure of t he d e vice or a d eteri or ati o n i n its effecti ve n ess, or a n y 
i na de q uac y i n its la belli n g or i n its t he directi o ns f or use; a n d 
•  Has le d t o t he d eat h or a s eri o us deteri or ati o n i n t he state of h ealt h of a patie nt, user 
or ot her pers o n or c o ul d d o s o were it t o rec ur.   
 
Preli mi nar y H ealt h Ca na da re p orti n g ti meli nes:  
•  Wit hi n 1 0 da ys after S p o ns or bec o mes a ware of a n i nci de nt, if t he i nci de nt has le d t o t he 
deat h or a s eri o us deteri orati o n i n t he state of healt h of a patie nt, user or ot h er pers o n, or  
•  Wit hi n 3 0 da ys after t he S p o ns or bec o mes a ware of a n i nci de nt, if t he i nci de nt has n ot 
le d t o t he deat h or a seri o us deteri orati o n i n t he state of healt h of a p atie nt, user or ot her 
pers o n, b ut c o ul d d o s o were it t o rec ur.  
 
1 2. 4.  A d verse E ve nt Cl assific ati o n   
 
A dverse Eve nt Severity   
Ear -relate d a d v erse e ve nts will be classifie d as t o t he se verit y of t he e ve nt base d o n t he 
defi niti o ns c o nsiste nt wit h A E se verit y  gra di n g  scale pr o vi de d b y t he Nati o nal Ca ncer 
I nstit ute, of t he NI H a n d U S De part me nt of Healt h a n d H u ma n Ser vices –  C o m m o n 
Ter mi n ol o g y Criteria f or A d verse E ve nts v. 4. 0 3 ( C T C A E)  J u ne 1 4, 2 0 1 0 (T a ble 5 ).6 6  
Gra de le vel of a d verse e v e nt refers t o t he se verit y of t he e v e nt. 
 
 
 
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6 4  of 8 1  
 
 
 
 
 
   
 
 
 
 
 
  
    
1 2. 6.  De vice M alf u ncti o ns  
A n y i n a de q u ac y of t he d e vice or pac ka gi n g wit h r es pect t o its i de ntit y or p erf or ma n ce will 
be rec or de d as a de vice malf u ncti o n. I nf or mati o n re gar di n g t he de vice i de ntit y (e g, de v ice 
na me/c o de a n d l ot n u m ber), te m p oral as pect of t he malf u ncti o n (e g, pri or t o o pe ni n g, 
d uri n g pre parati o n d uri n g pr oce d ure), n at ure of t he malf u ncti o n a n d rel ate d ness t o p ote ntial 
a d verse e ve nts will be c ollecte d o n a p pr o priate C R Fs.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 3. 0   S T A TI S TI C A L M E T H O D S   
T his pi v otal  st u d y i nte n ds t o e val uate effecti ve ness a n d safet y of  i o nt o p h oresis usi ng t he 
I P S a n d T D S f or T T pl ace me nt i n-office f or  c hil dre n i n dicate d f or t y m pa n ost o m y t u be 
place me nt (t he pi v otal c o h ort).  T he st u d y als o i ncl u des s u bjects e nr olle d i nt o O R lea d -i n 
a n d i n-offic e lea d -i n c o h orts. 
 
T he pi v otal p hase of t he st u d y ai ms t o c o nf ir m safet y, a n d d eter mine  w het h er t he i n -offi ce 
t u be place m e nt pr oce d ure ac hie ves acce pta ble pr oce d ural s ucc ess a n d t u be place m e nt 
t olera bilit y rates.  T h e pi v otal c o h ort will c o nsist of a sa m ple of 2 2 2  c hil dre n  wit h e val ua ble 
data  i ncl u di n g 10 2  c hil dre n a ge 5 t o 1 2 years ol d , a n d 1 2 0  c hil dre n less t ha n 5 years of a ge.  
T he re are t w o pri mar y e n d p oi nt s f or t he pi v otal c o h ort: ( 1) Pr oce d ural S uccess will be t he 
p r o p orti o n of s u bjects wit h T us ker Me di cal t y m p a n ost o m y t u b es place d i n all i n dicate d 
ears i n an  office pr oce d ure , a n d ( 2) T u be Place me nt T olera bilit y  will be t he mea n s u bject -
re p orte d p ai n sc ore f oll o wi n g T D S t u be place me nt usi n g t he Faces Pai n Scale-Re vise d 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6 5  of 8 1  
( F P S-R) (c hil dre n a ges 5 a n d ol der o nl y). T he statistical test s f or t he c o-pri mar y e n d p oi nt s 
are h y p ot h esis test s a gai nst p erf or ma n ce g o al s.  F urt her details re gar di n g t he statistical 
met h o ds ma y be f o u n d i n t he Statistical A nal ysis Pla n C P R 0 0 7 0 0 4 w hic h i ncl u des a n  
a p pe n de d A d a pti ve Desi g n Re p ort des cri bi n g t he pri mar y e n d p oi nt statistical m o del a n d 
o perati n g c haracteristics . 
 
1 3. 1.  Ge ner al St atistic al M et h o ds  
Descri pti ve statistics will be pr o vi de d . Data c ollecte d i n t he st u d y will be s u m marize d 
o verall a n d as d efi ne d i n t he pr ot oc ol .  
 
R o uti ne prese ntati o n of c o nti n u o us varia bles i n descri pti ve ta bles will i ncl u de mea n, 
sta n dar d de vi ati o n, sa m ple siz e, a n d me dia n. Cat e g orical or bi nar y varia bles will be 
prese nte d wit h n u merat or, de n o mi nat or, a n d perce nt .  
 
T he S A S s yste m ( v 9. 2  or later) or R Statistical pac ka ge ( 3. 2. 1 or hi g her) will be use d 
t o perf or m all statistical a nal yses.  
 
1 3. 2.  A n al ysis Sets   
1 3. 2. 1.  F ull  A n al ysis Set  
All s u bjects i n w h o m t he li d ocai ne is i ntr o d uce d i nt o t he ear ca nal a n d f or w h o m 
i o nt o p h oresis was i nitiate d will be i ncl u de d i n t he F A S .  
 
1 3. 2. 2.  Per Pr ot oc ol Set  
T he Per Pr ot o c ol Set is a s u bset of t he F A S a n d i ncl u des all F A S s u bjects wit h o ut 
maj or pr ot oc ol de viati o ns.  Maj or pr ot oc ol de viati o ns i ncl u de:  
•  Eli gi bilit y vi olati o ns  
•  Pr oce d ural d e viati o ns wit h t he p ote ntial t o affect a nest hesia efficac y (e g, 
a b bre viati o n of i o nt o p h oresis or use of i nc orrect l ocal a nest hesi a dr u g).  
 
1 3. 2. 3.  S afet y  A n al ysis Set  
T he Safet y A n al ysis Set will i ncl u de a ll pi v otal  c o h ort s u bjects i n w h o m t he li d ocai ne 
s ol uti o n is i ntr o d uce d i nt o t he ear ca nal. 
 
1 3. 3.  Pri m a r y E n d p oi nt A n al ysis  
Pr o ce d ur al S uccess:  T h e pr o p orti o n of s u bjects i n t he pi v otal c o h ort F A S  ac hie vi n g 
pr oce d ural s uccess will be e val uat e d a ga i nst a p erf or ma n ce g o al  of 6 8 % . T he st u d y 
desi g n e m pl o ys a Ba yesi a n hierarc hical gate kee p er strate g y w here b y t he test a gai nst 
t he perf or m a nce g o al occ urs i n t w o ste ps: 
 
1)  T he i nitial test a gai nst t h e perf or ma nce g oal is c o n d ucte d o n t he ol der c hil dre n i n 
t he pi v otal c o h ort, o nce t he st u d y has accr ue d e val ua ble data f or 1 0 2  c hil dre n a ges 
5 thr o u g h  1 2 years o f a ge.   
 
T he pri mar y h y p ot hesis is  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6 6  of 8 1  
 
 
Test 1:  
 
H o:  p 5 + ≤ 6 8 %  
vs.  
H a: p 5 + > 6 8 %  
 
W here p 5 + is t he pr o p orti o n of s u bjects 5 t hr o u g h 1 2 years ol d ac hie vi n g pr oce d ural 
s uccess.  
 
T his h y p ot h esis will be teste d usi n g a Ba yesi a n hierarc hical m o del e val uati n g 
w het her t he p osteri or pr o ba bilit y of H a is at least 0.9 7 5, w hic h is a nal o g o us t o a 
classical h y p ot hesis test at t he 0. 0 2 5 si g nifica n ce le vel i n t he F A S c o m prisi n g o nl y 
s u bjects 5 t hr o u g h 1 2 years ol d.  T his  Ba yesia n a n al ysis  a p plies t he test t o t he ol der 
gr o u p, w hile  b orr o wi n g  data fr o m all e nr olle d e v al ua ble s u bjects less t ha n 5 years 
ol d , as a p pr o priate gi ve n t he perf or ma n ce res ults at t he ti me of t he first test. 
 
 If t he ol der 
gr o u p ac hie v es t he p erf or ma nce g o al, t he sec o n d test is a p plie d t o t he y o u n ger 
s u bjects as descri b e d i n ste p 2 . 
 
 
 
2)  T he fi nal test f or t he pr oce d ural s u ccess pri mar y e n d p oi nt  is a p plie d o nce t he f ull 
pi v otal c o h ort is e nr olle d  (1 0 2  ol der s u bjects i n T est 1 , pl us 1 2 0  y o u n ger s u bjects 
a ges 6 m o nt hs t o less t ha n 5 years ol d ). T h e s ec o n d test e v al uates t he y o u n ger 
s u bjects a gai nst t he perf or ma nce g o al w hile b orr o wi n g dat a fr o m t he 1 0 2 ol der 
s u bjects usi n g a Ba yesia n hierarc hical m o del as a p pr o priate gi ve n t h e perf or ma nce 
of t he ol der gr o u p.  
 
Test 2:  
 
H o:  p < 5  ≤ 6 8 %  
vs.  
H a: p < 5  > 6 8 %  
 
W here p < 5  is t he pr o p orti o n of s u bjects i n t he y o u n ger gr o u p ( 6 m o nt hs thr o u g h  < 5  
years  ol d) ac hie vi n g pr oce d ural s uc cess.  
 
Test 2 is als o perf or me d usi n g a Ba yesia n hi erarc hical m o del, re q uiri n g a 9 7. 5 % 
p osteri or pr o ba bilit y of H a. 
 
 
 
 
 
 
 
 
 
T u be Pl ace me nt T oler a bilit y: Mea n s u bjec t-re p orte d pai n s c ore f oll o wi n g T D S t u be 
place me nt usi n g t he Faces Pai n Scale -Re vise d ( F P S -R). T he mea n pai n sc ore f or  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6 7  of 8 1  
s u bjects i n t he pi v otal c o h ort F A S, f or w h o m t u b e place me nt was s uccessf ul, will be 
e val uate d a gai nst a p erf or ma nce g o al of 4 .2  pai n s c ore .  
 
T he  test a gai nst t he perf or ma nce g oal is c o n d uct e d o n o nl y t he ol der c hil dre n i n t he 
pi v otal c o h ort, o nce t he st u d y ha s accr ue d e val ua ble data f or 1 0 2 c hil dre n a ges 5 
t hr o u g h 1 2 years of a ge.   
 
T he pri mar y h y p ot hesis is  
 
 
H o:  p 5 + ≥ 4 .2  
vs.  
H a: p 5 + <  4 .2  
 
W here p 5 + is t he mea n T u be Place me nt F P S -R f or  s u bjects 5 t hr o u g h 1 2 ye ars ol d.  
 
T his h y p ot hesis will be teste d usi n g a sta n dar d cl assical t -test at t he 0. 0 2 5 si g nifica n ce 
le vel i n t he F A S c o m prisi n g o nl y s u bj ects 5 t hr o u g h 1 2 years ol d. T u be Place me nt 
 
 
 
1 3. 4.   Sec o n d a r y Effic ac y E n d p oi nt A n al ys es  
Sec o n dar y e n d p oi nts will be teste d o n t he 1 0 2 ol der c hil dre n u p o n s uccessf ul 
ac hie ve m e nt of t he pri mar y e n d p oi nts.  If t h e 1 0 2 ol der c hil dre n pass t he test, a 
gat e kee p er d esi g n will b e e m pl o ye d a n d t h e sec o n dar y e n d p oi nts will be t este d o n t h e 
f ull pi v otal c o h ort o nce e nr olle d ( 1 0 2 ol der c hil dre n pl us 1 2 0  y o u n ger c hil dre n).  T he 
sec o n dar y e n d p oi nts (T u be P ate nc y, T u be R ete nti o n a n d A nest hesia E ffecti ve ness) are 
f u ncti o ns of t he t u be a n d i o nt o p h oresis de vice perf or ma nce a n d are n ot a ntici pate d t o 
var y b y s u bj ect a ge. T h eref ore,  testi n g t he sec o n dar y e n d p oi nts  o n t he f ull ( p o ole d) 
pi v otal c o h ort is a p pr o pri ate.  
 
1 3. 4. 1.  T U B E P A T E N C Y  
T u be Pate nc y is t he pr o p orti o n of s u bjects i n t he pi v otal c o h ort F A S , i n w hic h a T us ker 
Me dical t u be was s uccessf ull y place d,  wit h f u ncti o nal t u be pate nc y i n all s uccessf ull y 
treate d ears at t he 3 -wee k p ost -pr oce d ure f oll o w -u p visit . 
 
T he statistical test f or t he pi v otal c o h ort T u be P ate nc y s ec o n dar y e n d p oi nt is a 
h y p ot hesis test f or t he pr o p orti o n of s u bjects wit h f u ncti o nal t u be pate nc y  i n all 
s uccessf ull y tr eate d ears at t he 3-wee k f oll o w -u p visit a gai nst a t u be pate nc y 
p erf or ma n ce g o al.  T he  mi d -P 7 1 ,7 2 ,7 3 met h o d  f or a si n gle pr o p orti o n will be use d t o test 
 
H o: p ≤ 8 0 %  
Vs.  
H a: p > 8 0 %.  
 
T his e n d p oi nt will be c o nsi dere d met if t he p -v al ue fr o m t he test is less t ha n 0. 0 2 5.  
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 6 8  of 8 1  
 
 
1 3. 4. 2.  T U B E R E T E N TI O N  
 
T u be Rete nti o n is t he pr o p orti o n of s u bjects i n t he pi v otal c o h ort F A S , i n w hic h a 
T us ker Me dical t u be was s uccessf ull y place d,  wit h prese nce of a T us ker Me dical t u be 
acr oss t he t y m p a nic me m bra ne i n all s uccessf ull y tr eate d ears at t he 3 -wee k p ost -
pr oce d ure f oll o w -u p visit . 
 
T he statistical test f or t he pi v otal c o h ort T u be R ete nti o n sec o n dar y e n d p oi nt is a 
h y p ot hesis test f or t he pr o p orti o n of s u bjects wit h a T us ker  t ube  i n all s uccessf ull y 
treate d ears at t he 3 -w ee k f oll o w -u p visit a gai nst a T u be R ete nti o n p erf or ma nce g oal.  
A mi d -P  met h o d  f or a si n gle pr o p orti o n will be use d t o test 
H o: p ≤ 8 8 %  
Vs.  
H a: p > 8 8 %.  
 
T his e n d p oi nt will be c o nsi dere d met if t he p -v al ue fr o m t he test is less t ha n 0. 0 2 5.  
 
1 3. 4. 3.  A N E S T H E SI A E F F E C TI V E N E S S  
A nest hesia Effecti ve ness is t he pr o p orti o n of s u bjects i n t he pi v otal c o h ort F A S , w h o 
c o m plete d i o nt o p h oresis f or  all i n dicate d ears,  wit h a de q uat e a n est hesia f or 
t y m pa n ost o m y t u be pla ce me nt i n all treate d ears as deter mi ne d b y p h ysicia n’s 
e val uati o n of T M a n est hesia pri or t o t u be place m e nt.  
 
T he statistical test f or t he A nest hesia E ffecti ve ness sec o n dar y e n d p oi nt is a h y p ot h esis 
test f or t h e pr o p orti o n of s u bjects wit h a de q uat e a nest hesia f or t u b e  place me nt i n all 
ears c o m pleti n g i o nt o p h oresis a gai nst an  A nest h esia E ffecti ve ness p erf or ma nce g oal.  
T he mi d -P met h o d  f or a si n gle pr o p orti o n will be use d t o test 
H o: p ≤ 8 5 %  
Vs.  
H a: p > 8 5%.  
 
T his e n d p oi nt will be c o nsi dere d met if t he p -v al ue fr o m t he test is less t ha n 0. 0 2 5.  
 
 
 
 
 
 
   
 
 
 
 
   
 
   
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 0  of 8 1  
 
 
1 3. 6.  S afet y A n al ys is 
All re p orte d or o bser ve d a d verse e ve nts t hat o cc ur f or s u bjects i n t he Safet y A nal ysis 
Set d uri n g or after t h e pr oce d ure will be rec or de d.  
 
T he st u d y will pres e nt t he t otalit y of safet y data, b y s u bject i ncl u di n g:  
•  Seri o us de vice, pr oce d ure , a n d dr u g-relate d e ve nts 
•  Ot her seri o us e v e nts  
•  N o n -seri o us de vic e, pr oce d ure, dr u g-rel ate d e v e nts 
•  Ot her n o n -seri o us e ve nts 
 
T hese dat a will als o be re p orte d i n t h e Lea d -i n O R a n d Lea d-i n Office c o h orts. 
 
 
 
All A Es will be ta b ulate d b y preferre d ter ms a n d s yste m or ga n cl ass usi n g t he Me dical 
Dicti o nar y f or Re g ulat or y Acti vities ( Me d R A).  T he fre q u e nc y of eac h e v e nt will be 
s u m marize d b y s eri o us ness, se verit y a n d b y relati o ns hi p t o t he st u d y de vice, pr oce d ure 
a n d/ or dr u g. I n t he e v e nt a s u bject re p orts t he sa me e ve nt se veral ti mes (e g, otal gia), 
t he first occ urre nce of t h e w orst re p orte d case of t he e ve nt will be use d f or t he p ur p ose  
of a nal ysis. D urati o n a n d o utc o me of A Es will be re p orte d i n s u bject li ne listi n gs . 
 
 
      
 
  
 
 
 
 
 
 
 
      
 
  
 
 
 
 
 
 
 
      
  
 
  
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 2  of 8 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 3. 8.  H a n dli n g Dr o p O uts or Missi n g D at a  
T he n u m ber a n d pr o p orti o n of s u bjects eli gi ble f or a n d c o m plia nt wit h all f oll o w -u p 
e x a mi nati o ns will be pres e nte d . S u bjects w h o wit h dra w fr o m t he st u d y will be ta b ulate d 
wit h t he reas o ns f or t he wit h dra wal . S u bjects w h o i nitiate t he pr oce d ure, re gar dless of 
t olera bilit y o utc o me or a nest hesia effecti ve ness, will be e nc o ura ge d t o ret ur n f or all 
f oll o w-u p assess me nts.   
 
Se nsiti vit y a nal yses a n d h a n dli n g of missi n g data is descri b e d i n t he Statistical A nal ysis 
Pla n C P R 0 0 7 0 0 4.  
 
 
  
  
 
 
  
  
  
  
  
  
 
 
 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 4  of 8 1  
st u d y, a ge n ui ne eff ort m ust be ma de t o deter mi ne t he reas o n(s) w h y t he s u bject faile d t o 
ret ur n f or t he pr oce d ure or f oll o w-u p  visit or disc o nti n ue d t he st u d y, a n d t he reas o n m ust 
be rec or de d o n t he a p pr o priate C R F.  
 
P ote ntial reas o ns f or disc o nti n uati o n i ncl u de:  
 
•  S u bject  or s u bject’s care gi ver  deci des it is i n t he s u bject’s best i nterest  t o wit h dra w 
 
•  S u bject e x presses  i nt olera nce or disc o mf ort d uri n g t h e pr oce d ure a n d s u bject or 
s u bject’s care gi ver i n dicates t he y wis h t o st o p t he pr oce d ure a n d wit h dr a w 
 
 
•  I n v esti gat or deci d es if a seri o us a d verse e v e nt  re q uires wit h dra wal fr o m t he st u d y 
 
•  I n v esti gat or deci des it is i n t he s u bject’s best i nterest t o be wit h dra w n if s u bject is 
e x perie nci n g i nt olera nce or i nt olera ble reacti o n t o t he pr oce d ure.  
 
 
  
 
 
 
 
 
  
 
 
 
 
If a  s u bject disc o nti n ues partici pati o n i n t he st u d y, t he I n vesti gat or will atte m pt t o ha ve t he 
s u bject c o nti n ue partici pati o n t o c o m plete f oll o w -u p assess me nts u nless t he s u bject’s safet y 
is c o m pr o mise d.  All Seri o us A d verse E ve nts t hat ha ve n ot res ol ve d b y t he e n d of t he 
s u bject's partici pati o n i n t he st u d y, m ust be f oll o we d u ntil t he e ve nt res ol ves, sta b ilizes or 
bec o mes n o n -s eri o us.  
 
All p ote ntial s u bjects i n t he st u d y will be ver ball y i nf or m e d a n d will si g n a n i nf or me d 
c o nse nt i n c o m plia nce wit h 2 1 C F R § 5 0 t hat states t hat a n y wit h dra wal fr o m t he st u d y will 
neit her prej u dice n or i n a n y w a y affect t heir f ut ure treat me nt.  
 
Pri or t o desi g nati n g a s u bject as l ost t o f oll o w -u p, t he site m ust pr o vi de d oc u me nte d 
e vi de nce of t hree ( 3) g o o d fait h atte m pts t o c o ntact t he s u bject t o w hic h t here has b ee n n o 
res p o nse. At t h at p oi nt t he s u bject will be c o nsi dere d l ost -t o-f oll o w-u p a n d wit h dra w n fr o m 
t he st u d y. 
 
1 5. 2.  St u d y St o p pi n g Crite ri a   
T he S p o ns or or I n vesti gat or ma y ter mi nate t he st u d y or ce nter p artici pati o n at a n y ti me f or 
reas o na bl e ca us e, a n d will pr o vi de s ufficie nt n otifi cati o n.  
 
Reas o ns f or pre mat ure s us pe nsi o n of t he trial i ncl u de, b ut are n ot li mite d t o: 
 
•  Ris k t o S u bjects  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 5  of 8 1  
 
•  Lac k of effecti ve ness  
 
 
•  I n a de q uat e e nr oll me nt  
 
•  B usi ness reas o ns  
 
Reas o ns f or pre m at ure t er mi nati o n of a n i n vesti gati o nal site i ncl u de, b ut are n ot li mite d t o: 
 
•  Si te is n o n-c o m plia nt t o pr ot oc ol, pr oce d ures or G C P  
 
•  I n a de q uat e e nr oll me nt  
 
Reas o ns f or  pre mat ure s us pe nsi o n of e nr oll me nt i ncl u de b ut are n ot li mite d t o:  
•  
3  seri o us Gra de 3 or hi g her u ne x pecte d dr u g, de vice or pr o ce d ure -rel ate d 
a d verse e ve nts . 
 
 
  
 
At t he p oi nt t he site or st u d y is ter mi nate d, t h e site will i m me diatel y i n v o k e all pr oce d ures   
 
re q uire d at t he 3 -wee k f oll o w -u p visit .  
 
All p ote ntial s u bjects i n t he st u d y will be ver ball y i nf or me d, a n d will si g n a n i nf or me d 
c o nse nt i n c o m plia nce wit h 2 1 C F R § 5 0 t hat states t hat st u d y t er mi nati o n will neit her 
prej u dice n or i n a n y wa y affect t heir f u t ur e treat m e nt. 
 
1 6. 0  I N V E S TI G A T O R R E S P O N SI BI LI T IE S  
I n v esti gat ors w h o partici pate i n t his st u d y will c o n d uct t he st u d y acc or di n g t o t he pr ot oc ol, 
t he Decl arati o n of Helsi n ki, G C P a n d a p plica ble re g ul at or y re q uire me nts. T us ker Me dical  
will s p o ns or t he c o n d u ct of t he st u d y at a p pr o xi matel y 2 5  i n vesti gati o nal ce nters. T his  
st u d y will be perf or me d u n der t he directi o n a n d res p o nsi bilit y of t he p h ysicia n i n vesti gat or 
at eac h st u d y site . It is t he res p o nsi bilit y of t he I n vesti gat ors t o e ns ure st u d y material is 
re vie we d a n d a p pr o ve d b y all a p plica ble I nstit uti o nal Re vie w B oar ds (I R B), h os pital 
c o m mittees, a n d a d mi nistrati ve pers o n nel as re q uire d .  
 
T he I n vesti gat or is res p o nsi ble f or t he e x ec uti o n of t he st u d y, pr o per perf or ma n ce of 
partici pati n g pers o n n el, e ns uri n g a d here nce t o t he pr ot oc ol a n d s c he d ule of pr oce d ures , a n d 
f or t he c o ntr ol of d e vic es u n der i n vesti gati o n. T he I n vesti gat or is als o res p o nsi ble f or 
pr otecti n g t h e ri g hts, safet y, a n d welfare of s u bj ects u n der t he i n vesti gat or's care, a n d 
e ns uri n g t h at writte n i nf or me d c o nse nt is o btai ne d.  
 
T he I n vesti gat or is res p o nsi ble f or data c o nfi de ntialit y, q u alit y, a n d c o m plete ness, a n d 
pr o per d ata st ora ge i n a s ec ure file f or a peri o d of ti me as i n dicate d i n t h e pr ot oc ol, Cli nical 
Trial A gree me nt ( C T A) a n d if ma n date d, b y t he res pecti ve I R Bs.  
 
T he I n vesti gat or a n d site pers o n nel directl y i n v ol v e d wit h t he st u d y will recei ve trai ni n g i n 
t he pr ot oc ol a n d use of de vices pri or t o i nitiati o n of t he st u d y . T his trai ni n g will be 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 6  of 8 1  
c o n d ucte d b y t h e S p o ns or ( T us ker Me dical , I nc.) or desi g n ee, pri or t o i nitiati o n of t he 
st u d y.  
 
 
1 7. 0  S P O N S O R  
T us ker Me dical , I n c. is t he de vice ma n ufact ur er as well as t he st u d y s p o ns or (“ S p o ns or”). 
T he S p o ns or will w or k wit h t he st u d y site u n d er t h e ter ms of t he Cli nical Trial A gree me nt 
( C T A).  
 
T he S p o ns or c o ntact is as f oll o ws:  
 
T us ker Me dic al , I nc. 
1 5 5 J effers o n  Dri ve  
Me nl o Par k, C A 9 4 0 2 5  
 
 
 
 
  
 
 
1 8. 0   M O NI T O RI N G  
T us ker 
Me dic al , I nc. ( S p o ns or) or desi g nee will m o nit or t he st u d y sites t o e ns ure 
i n vesti gat ors are i n c o m plia nce  wit h t he pr ot oc ol; s u bject i nf or me d c o nsent f or ms are 
pr o perl y c o m plete d;  a d e q uate pr otecti o n of t he ri g hts of t he h u ma n s u bjects a n d t he q ualit y 
a n d i nte grit y of t he res ulti n g data ; st u d y dat a is verifie d a gai nst s o urce d oc u me nts f or ke y 
safet y a n d effecti ve n ess varia bles ; i n vesti gati o nal de vices  a n d dr u g are pr o perl y c o ntr olle d;  
a n d verific ati o n t hat re p orts are file d i n acc or da n ce wit h t he pr ot oc ol an d t he a p pr o pri ate 
re g ulati o ns. M o nit ori n g 
will be c o n d uct e d acc or di n g t o t he S p o ns or’s 
m o nit ori n g 
pr oce d ure a n d st u d y m o nit ori n g pla n.  
 
1 9. 0  I N V E S TI G A TI O N A L P R O DU C T A C C O U N T A BI LI T Y  
Access t o i n vesti gati o nal dr u g a n d de vices s hall be c o ntr olle d a n d t he i n vesti gati o nal dr u g 
a n d de vices s hall be use d o nl y i n t he cli nical i n vest i gati o n a n d acc or di n g t o t he pr ot oc ol. 
T he S p o ns or s hall kee p rec or ds t o d oc u me nt t he p h ysic al l ocati o n of all i n vesti gati o nal 
dr u g a n d de vices fr o m s hi p me nt t o t he i n vesti gati o n sites u ntil ret ur n or dis p osal . Dr u g a n d 
de vices will be st ore d acc or di n g t o pr o d uct la beli n g. T h e pri n ci pal i n v esti gat or or a n 
a ut h orize d desi g n ee s h all kee p rec or ds d oc u me nti n g t he recei pt, use, ret ur n, a n d dis p osal 
of t he i n vesti gati o nal dr u g a n d de vices, w hic h s hall i ncl u de (a) t he date of recei pt, ( b) 
i de ntificati o n of eac h i n vesti gati o nal dr u g a n d de vice ( batc h n u m ber/s erial n u m ber or 
u ni q ue c o de), (c) t he e x pirati o n date, ( d) t he dat e or dates of use, (e) s u bject i de ntificati o n, 
a n d (f) t h e date of ret ur n of u n use d, e x pire d or malf u ncti o ni n g i n vesti gati o nal pr o d ucts , if 
a p plica ble.  
 
2 0. 0  D E VI A TI O N S  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 7  of 8 1  
A pr ot oc ol de viati o n is defi ne d as a n y e v e nt w here t he I n vesti gat or or site pers o n nel de viate 
fr o m t he st u d y pr ot oc ol or st u d y pr oce d ures f or a n y reas o n. It is t he I n vesti gat or’s 
res p o nsi bilit y t o e ns ure t h at t here are n o pr ot oc ol de viati o ns t hr o u g h o ut t he life of t he st u d y . 
I n t he e v e nt t hat a n o n-e mer ge nc y pr ot oc ol d e viati o n is i de ntifie d, at t he ti me of 
i de ntificati o n, t he pers o n nel i de ntif yi n g t he e ve nt will re vie w a n d defi ne a p pr o priat e 
c orrecti ve acti o ns t o pre ve nt re c urre n ce . T h e I R B will be n otifie d as a p plica ble.  A n y 
de viati o ns fr o m t his pr ot oc ol will be d oc u me nte d b y t he site o n a pr ot oc ol de viati o n C R F .  
 
2 1. 0   D A T A H A N D LI N G A N D R E C O R D K E E PI N G  
2 1. 1.  S o urce D at a a n d C ase Re p ort F o r ms  
All st u d y d ata will be ca pt ure d o n s o urce  d o c u me nts b y t he I n vesti gati o nal Site . Data 
fr o m t he s o urce d o c u me nts will be rec or de d t o C R Fs b y site pers o n nel t hat ha ve bee n 
trai ne d o n t he pr ot oc ol a n d C R F c o m pleti o n .  
 
 
2 1. 2.  D at a Q u alit y Ass ur a nce  
Acc urac y a n d relia bilit y of t he cli nical st u d y d ata will be  e ns ure d  b y selecti o n of 
q ualifie d i n vesti gat ors, a n d a p pr o pri ate st u d y ce nters, re vi e w of pr ot oc ol pr oce d ures 
wit h t he i n vesti gat ors a n d ass ociate d pers o n nel pri or t o t he st u d y, a n d b y peri o dic 
m o nit ori n g visits b y t he s p o ns or. C R Fs will be  re vie we d f or acc urac y a n d c o m plete ness 
b y t he s p o ns or d uri n g o n site m o nit ori n g visits a n d after t heir ret ur n t o t he s p o ns or, a n d 
a n y discre p a ncies w ill be res ol ve d wit h t he i n vesti gat or or desi g nees, as a p pr o priate.  
 
2 1. 3.  Rec or d Ret e nti o n  
All cli nical sites will mai ntai n all rec or ds pertai ni n g t o t his st u d y f or a mi ni m u m of t w o 
years after mar k eti n g a p pr o val or f or mal disc o nti n uati o n of i n vesti gati o nal pr o d uct 
de vel o p me n t. T he S p o ns or will n otif y t h e cli nical sites of t he d ate of  disc o nti n uati o n. 
N o st u d y -relate d rec or ds, writte n or electr o nic, will be destr o ye d or tra nsferre d wit h o ut 
s pecific writte n a p pr o val b y t he S p o ns or.  
 
2 2. 0   P U B LI C A TI O N P O LI C Y  
T he C T A m ut uall y si g n e d b y t he I n vesti gat or(s) a n d T us k er M e dical , I n c., defi n es a n d 
descri bes t he n at ure of t h e st u d y a gree me nt.  
 
T he S p o ns or retai ns t he ri g hts t o t his pr ot oc ol  a n d t he C R Fs bef ore a n d after data e ntr y. 
T us ker Me dic al , I nc. reser ves t he ri g ht t o re vie w a n y re p orts of t his st u d y t o verif y t hat t he 
i nf or mati on is acc urate a n d t o e ns ure t he c o nte nt a n d ti mi n g of a n y s uc h p u blicati o n is 
m ut uall y a gree d u p o n b y t he I n vesti gat or(s) a n d T us ker Me dical , I nc. Draft a bstr acts, 
ma n uscri pts, a n d materials f or prese ntati o n at scie ntific meeti n gs s h o ul d be pr o vi de d t o t he  
s p o ns or at least 3 0 w or ki n g da ys pri or t o s u b missi o n. 
 
Cli nical trial i nf or mati o n will be re gistere d i n t he cli nical trial re gistr y data ba n k mai ntai ne d 
b y t he Nati o nal I nstit utes of Healt h/ Nati o nal Li brar y of Me dici n e ( NI H/ N L M)  per F D A A A 
8 0 1 re q uire me nts . If a f ut ure p u blicati o n res ults fr o m t his st u d y, aut h ors hi p will be 
esta blis he d acc or di n g t o I C MJ E g ui deli nes.  

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 8  of 8 1  
 
 
 
2 3. 0   R E F E R E N C E S  
1 R ose nfel d R M, Sc h wart z S R, P y n n o n e n M A, T u n kel D E, H usse y H M, Fi c hera J S, Gri mes 
A M et al. Cli nical practice g ui d eli ne: t y m pa n ost o m y t u bes i n c hil dre n. Ot olar y n g ol Hea d 
Nec k S ur g, 2 0 1 3; 1 4 9(I S): S 1 -S 3 5.  
2 Otitis Me dia ( Ear I nfecti o n), NI D C D, J ul y 2 0 0 2. NI H P u b N o. 9 7 -4 2 1 6. 7 A u g 2 0 0 8 
htt p:// w w w. ni dc d. ni h. g o v/ healt h/ heari n g/  otitis m.as p.  
3 Klei n J, Pelt o n S. E pi de mi ol o g y, p at h o ge nesis, cli nical ma nifestati o ns, a n d c o m plica ti o ns of 
ac ute otitis me dia.  U p t o Date, Oct o b er 2 0 0 8, 7 A u g 2 0 0 8.  
4  T us ker Me dical a n al ysis of Tr u ve n C o m merci al, Me dicai d a n d Me di care data bases.  
5 Lit ma n R S. Basics of Pe diatric A nest hesia. P hila del p hia, P A, 2 0 1 3.  
6 De w hirst E, Fe del G, Ra ma n V et al. Pai n ma na ge me nt f oll o wi n g m yri n g ot o m y a n d t u be 
place me nt: I ntra n asal de x me det o mi di ne vers us i ntra n asal f e nta n yl. I nt J Pe diatr 
Ot or hi n olar y n g ol , 2 0 1 4; 7 8( 7): 1 0 9 0-1 0 9 4 . 
7 M o nta g u e M L, Lee M S W, H ussai n S S M. H u ma n err or i de ntifi cati o n: a n a nal ysis of 
m yri n g ot o m y a n d ve ntilati o n t u be i nserti o n. Arc h Ot olar y n g ol Hea d Nec k S ur g, 
2 0 0 4; 1 3 0: 1 1 5 3 -1 1 5 7.  
8  Isaacs o n G. Si x s i g ma t y m pa n ost o m y t u be i nserti o n: a c hie vi n g t he hi g hest safet y le v els 
d uri n g resi de nc y tr ai ni n g. O t olar y n g ol Hea d Nec k S ur ger y, 2 0 0 8; 1 3 9: 3 5 3-3 5 7.  
 
 
 
 
1 0 Free ma n S R M, Is eli C E, Kerr M B A, K o n g J H K, Gi bs o n W P R . P he n ol a p plicati o n f or 
t y m pa nic me m bra ne a nest hesia. Cli n Ot olar y n g ol, 2 0 0 7; 3 3: 1 5 2 -1 9 9 . 
1 1  E M L A dr u g la b el; 
h tt p:// dail y me d. nl m. ni h. g o v/ dail y me d/arc hi ves/f da Dr u gI nf o.cf m? arc hi vei d = 1 2 4 0, accesse d 
0 3J u ne 2 0 1 6.  
1 2 J y va k or pi M. A c o m paris o n of t o pical E M L A crea m wit h B o nai n’s s ol uti o n f or a nest hesi a 
of t he t y m pa ni c me m bra ne d uri n g t y m pa n o ce ntesis. E ur Arc h Ot or hi n olar y n g ol , 1 9 9 6; 2 5 3: 
2 3 4 -2 3 6.  
1 3 T o d d N. W hat y o ur c ollea g ues t hi n k of t y m pa n ost o m y t u bes 2 8 years later. Lar y n g osc o p e , 
1 9 9 9; 1 0 9: 1 0 2 8 -1 0 3 2.  
1 4  Mar k o witz -S pe nce L, Br o ds k y L, S ye d N, Sta nie vic h J, V ol d M. A nest hetic C o m plicati o ns 
of T y m p a n ost o m y T u b e Place me nt i n C hil dre n. Arc h Ot olar y n g ol H ea d Nec k S ur g, 2 0 0 6; 
1 1 6: 8 0 9 -8 1 2.  
1 5  H off ma n n  K K, T h o m ps o n G K, B ur ke B L, Der ka y C S. A nest hetic C o m plicati o ns  of 
T y m pa n ost o m y T u be Pla ce me nt i n C hil dre n. Arc h Ot olar y n g ol Hea d Nec k S ur g , 2 0 0 2; 1 2 8: 
1 0 4 0 -1 0 4 3.  
1 6  I n g C, Di ma g gi o C, W hite h o use A et al.  L o n g -t er m differe n ces i n la n g ua ge a n d c o g niti ve 
f u ncti o n after c hil d h o o d e x p os ure t o a nest hesia. Pe diatrics, 2 0 1 2; 1 3 0: e 4 7 6.  
1 7  Wil d er R T, Flic k R P, S pr u n g J et al.  Earl y e x p os ure t o a nest hesia a n d lear ni n g disa bilities 
i n a p o p ulati o n- base d birt h c o h ort. A nest hesi ol o g y , 2 0 0 9; 1 1 0: 7 9 6. 
1 8  Bl oc k RI, M a g n otta V A, Ba y ma n E O, et al. Are a nest hesia a n d s ur ger y d uri n g i nfa n c y 
ass ociate d wit h decrease d w hite matter i nte grit y a n d v ol u me d uri n g c hil d h o o d? 
A nest hesi ol o g y e p u b bef ore pri nt, 2 0 1 7.  
                                                 

T us ker Me dic al , I nc. 
    
C o nfi de ntial  
C P R 0 0 7 0 0 1  Re v E  
Effecti ve: 1 1/ 1 0 / 2 0 1 7 
 
Pa ge 7 9  of 8 1  
                                                                                                                                                        
1 9 I n g C, S u n M, Olfs o n M, et al. A ge at e x p os ure t o s ur ger y a n d a nest hesia i n c hil dre n a n d 
ass ociati o n wit h me ntal dis or der dia g n osis. A nest h A nal g, 2 0 1 7, e p u b a h ea d of pri nt.  
2 0 F D A Dr u g Safet y C o m m u nicati o n: F D A re vi e w res ults i n ne w war ni n gs a b o ut usi n g 
ge n eral a nest hetics a n d s e dati o n dr u gs i n y o u n g c hil dre n a n d pre g n a nt w o me n. 1 2/ 1 4/ 2 0 0 6, 
htt p:// w w w.f da. g o v/ Dr u gs/ Dr u g Safet y/ uc m 5 1 9 6 1 6. ht m.  
2 1 Br o w ni n g G G. A dj u va nt a de n oi dect o m y i n persiste nt bilateral otitis me dia wit h eff usi o n: 
Heari n g a n d re visi o n s ur ger y o utc o mes t hr o u g h 2 years i n t he T A R G E T ra n d o mize d trial. 
Cli n Ot olar y n g ol 3 7: 1 0 7 -1 1 6, 2 0 1 2.    
2 2 Valt o ne n H, T u o mile ht o H, Q var n ber g Y, N u uti n e n J. A 1 4 -Year pr os p ecti ve f oll o w -u p 
st u d y of c hil dre n treate d earl y i n life wit h t y m p a n ost o m y t u bes: Part 1: Cli nical O utc o mes. 
Arc h Ot olar y n g ol H ea d Nec k S ur g 1 3 1: 2 9 3 -2 9 8, 2 0 0 5.  
2 3  Kai n Z N, M a yes L C,  O’ C o n n or T Z, Cicc h etti D V. Pre o perati ve a n xiet y i n c hil dre n, 
Pre dict ors a n d o utc o mes. Arc h Pe diatr A d ol esc M e d , 1 9 9 6; 1 5 0: 1 2 3 8-4 5.  
2 4  Kai n Z N, M a yes L C, Cal d well -A n dre ws A A et al. Slee pi n g C haracteristics of C hil dre n 
U n der g oi n g O ut patie nt Electi ve S ur ger y.  A nest hesi ol o g y , 2 0 0 2; 9 7: 1 0 9 3-1 0 1.  
2 5 C h or ne y J M, Kai n A N. Be ha vi oral a nal ysis of c hil dre n’s res p o nse t o i n d u cti o n of 
a nest hesia. A n est h A nal g, 2 0 0 9; 1 0 9: 1 4 3 4 -4 0.  
2 6 Ber g h m a ns J M, P ole y MJ, va n der E n de J, et al. A Vis ual a nal o g scale t o assess a n xiet y i n 
c hil dre n d uri n g a n est hesia i n d ucti o n ( V A S -I): Res ults s u p p orti n g its vali dit y i n a sa m ple of 
da y care s ur ger y patie nts. Pe diatric A nest hesia, 2 0 1 7; D OI: 1 0. 1 1 1 1/ p a n. 1 3 2 0 6.  
2 7 Sa de hi A, Ta bari A K, M a h da vi A, Salaria n S, Raza vi S S. I m pact of pare nt al prese n ce  
d uri n g i n d ucti o n of a nest hesia o n a n xiet y le vel a m o n g pe di atric patie nts a n d t heir pare nts: a 
ra n d o mize d cli nical trial. Ne ur o ps yc hiatr Dis Treat, 2 0 1 7; 1 2: 3 2 3 7-3 2 4 1.  
2 8 Stric ker P A, M u hl y W T, J a ntze n E C, et al. I ntr a m usc ular fe nt a n yl a n d ket or olac ass oci ate d 
wit h s u peri or pai n c o ntr ol after pe di atric bilateral m yri n g ot o m y a n d t u be pl ace me nt s ur ger y: 
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