Evaluation of Long-term Patient Experience With a Medtronic Closed-Loop Spinal Cord Stimulation System
Phase: NA
Conditions: Low Back Pain, Leg Pain, Upper Limb Pain
Sponsor: MedtronicNeuro

 
M e dtr o nic Cl os e d -L o o p S pi n al C or d Sti m ul ati o n Syst e m 
N C T:  N C T 0 5 1 7 7 3 5 4  
D at e: 2 4 F E B 2 0 2 3  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 of 1 1 7   
 
 
 
 
 
 
 
Cli nic al I n v esti g ati o n Pl a n  
Cli nic al I n v esti g ati o n Pl a n/ St u d y Titl e  E v al u ati o n of L o n g -t er m P ati e nt Ex p eri e nc e wit h 
a M e dtr o nic Cl os e d -L o o p S C S S yst e m ( Cl os e d-
L o o p S C S st u dy) 
Cli nic al I n v esti g ati o n Pl a n I d e ntifi er  M D T 2 1 0 1 7  
St u d y Pr o d uct N a m e  P ai n R ec h ar g e a bl e  (R C ) s yst e m wit h I nc e ptiv™ 
I m pl a nt a bl e N e ur osti m ul at or (I N S) 
S p o ns or/L oc al S p o ns or  M e dtr o nic  N e ur o m o d ul ati o n  
 
 
 
 
M e d tr o nic A ustr al asi a Pt y Lt d 
 
 
 
D oc u m e nt V ersi o n  4 . 0  
V ersi o n D at e  0 6J A N 0 2 3  
C o nfi d e nti alit y St at e m e nt  
T h e  i nf or m ati o n c o nt ai n e d i n t his d oc u m e nt  is c o nfi d e nti al a n d  t h e pr o pri et ary  pr o p erty  of  
M e dtr o nic.  A ny  distri b uti o n,  c o pyi n g, or  discl os ur e  wit h o ut  t h e pri or  writt e n  a ut h oriz ati o n  of  
M e dtr o nic  is strictly pr o hi bit e d.  P ers o ns  t o w h o m  t h e i nf or m ati o n is discl os e d m ust  k n o w  t h at it is 
c o nfi d e nti al a n d  t h at it m ay  n ot  b e  f urt h er discl os e d by  t h e m. 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 of 1 1 7   
 
 
 
 
 
1.  I n v e sti g at or A gr e e m e nt a n d Si g n at ur e P a g e  
 
St u d y pr o d uct N a m e  
P ai n R C s yst e m wit h I nc e pti v™ I N S 
S p o ns or  
M e dtr o nic  N e ur o m o d ul ati o n  
Cli nic al I n v esti g ati o n Pl a n I d e ntifi er  
E v al u ati o n of L o n g -t er m P ati e nt Ex p eri e nc e wit h a 
M e dtr o nic Cl os e d -L o o p S CS S yst e m  ( Cl os e d-L o o p S C S 
st u dy) 
V ersi o n N u m b er/ D at e  
4. 0  0 6J A N 2 0 2 3  
I h av e r e a d t h e pr ot oc ol, i ncl u di n g all a p p e n dic es, a n d I a gr e e t h at it c o nt ai ns all n ec ess ary d et ails f or 
m e a n d my st aff t o c o n d uct t his st u dy as d escri b e d. I  will c o n d uct t his st u dy as o utli n e d h er ei n a n d 
will m ak e a r e as o n a bl e eff ort t o c o m pl et e t h e st u dy wit hi n t h e ti m e d esi g n at e d.  
I a gr e e t o c o m pl y wit h t h e D ecl ar ati o n of H elsi n ki, t h e Cli nic al I nv esti g ati o n Pl a n, a n d G o o d Cli nic al 
Pr actic e, as w ell as l oc al l a ws, r e g ul ati o ns , a n d st a n d ar ds.  I a gr e e t o e ns ur e t h at t h e c o nfi d e nti al 
i nf or m ati o n c o nt ai n e d i n t his d oc u m e nt will n ot b e us e d f or a ny p ur p os e ot h er t h a n t h e ev al u ati o n 
a n d c o n d uct of t h e cli nic al i nv esti g ati o n wit h o ut t h e pri or writt e n c o ns e nt of M e dtr o nic.  
I will pr ovi d e all st u dy p ers o n n el u n d er m y s u p ervisi o n c o pi es of t h e pr ot oc ol a n d acc ess t o all 
i nf or m ati o n pr ovi d e d by M e dtr o nic.  I will disc uss t his m at eri al wit h t h e m t o e ns ur e t h at t h ey ar e f ull y 
i nf or m e d a b o ut t h e pr o d ucts a n d t h e st u dy. 
I n v esti g at or’s Si g n at ur e 
 
I n v esti g at or’s N a m e 
 
I nstit uti o n 
 
D at e  
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 of 1 1 7   
 
 
 
 
 
T a bl e of C o nt e nt s  
1.  
I n v e sti g at or A gr e e m e nt a n d Si g n at ur e P a g e  .................................................................... 2 
T a bl e of C o nt e nt s  ...................................................................................................................... 3 
2.  
Gl o s s ar y  .............................................................................................................................. 9 
3.  
S y n o p si s  ...........................................................................................................................  1 1  
4.  
I ntr o d u cti o n  .....................................................................................................................  1 9  
4. 1  B a c k gr o u n d  ........................................................................................................................... 1 9  
4. 2  P ur p os e  ................................................................................................................................ . 2 3  
5.  
O bj e cti v e s  ........................................................................................................................  2 4  
5. 1  Pri m ar y O bj e cti v es  ................................................................................................................. 2 4  
5. 2  S e c o n d ar y O bj e cti v es  ............................................................................................................. 2 4  
 
6.  
St u d y D e si g n  ....................................................................................................................  2 5  
6. 1  D ur ati o n  ................................................................................................................................  2 6  
6. 2  R ati o n al e ...............................................................................................................................  2 6  
7.  
Pr o d u ct D e s cri pti o n .......................................................................................................... 2 6  
7. 1  G e n er a l ................................................................................................................................ . 2 6  
7. 1. 1  
I nc e pti v I m pl a nt a bl e N e ur osti m ul at or ............................................................................... 3 0  
7. 1. 2  
V ectris S ur e Sc a n M RI 1x 8 C o m p act  .................................................................................... 3 1  
7. 1. 3  
S p ecif y S ur e Sc a n M RI 5 - 6- 5 ................................................................................................ 3 1  
7. 1. 4  
Wir el ess Ext er n al N e ur osti m ul at or  ..................................................................................... 3 1  
7. 1. 5  
V ectris M RI 1x 8 C o m p act  .................................................................................................... 3 1  
7. 1. 6  
B o ot  ..................................................................................................................................... 3 1  
7. 1. 7  
Cli nici a n T a bl et  .................................................................................................................... 3 1  
7. 1. 8  
Cli nici a n Pr o gr a m m er A p plic ati o n  ...................................................................................... 3 1  
7. 1. 9  
P ati e nt Pr o gr a m mi n g A p plic ati o n  ....................................................................................... 3 1  
7. 1. 1 0  
Sti m ul ati o n Tri ali n g Cli nici a n Pr o gr a m m er A p plic ati o n  ...................................................... 3 2  
7. 1. 1 1  
P ati e nt Pr o gr a m m er Tri ali n g A p plic ati o n  ........................................................................... 3 2  
7. 1. 1 2  
P ati e nt T el e m etry C o m m u nic at or  ...................................................................................... 3 2  
7. 1. 1 3  
C o m m u nic at or  .................................................................................................................... 3 2  
7. 1. 1 4  
C o n n ect or Pl u g  .................................................................................................................... 3 2  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 of 1 1 7   
 
 
 
 
 
7. 1. 1 5  
R ec h ar g er S u bsyst e m  .......................................................................................................... 3 2  
7. 2  M a n uf a ct ur er  ......................................................................................................................... 3 2  
7. 3  P a c k a gi n g  .............................................................................................................................. 3 3  
7. 4  I nt e n d e d P o p ul ati o n ............................................................................................................... 3 3  
7. 5  E q ui p m e nt  ............................................................................................................................. 3 3  
7. 6  Pr o d u ct Us e  ........................................................................................................................... 3 3  
7. 7  Pr o d u ct Tr ai ni n g M at eri als  ...................................................................................................... 3 3  
7. 8  Pr o d u ct R e c ei pt a n d Tr a c ki n g  ................................................................................................. 3 3  
7. 9  Pr o d u ct St or a g e  ..................................................................................................................... 3 3  
7. 1 0  Pr o d u ct R et ur n  ...................................................................................................................... 3 3  
7. 1 1  Pr o d u ct A c c o u nt a bilit y  ............................................................................................................ 3 4  
8.  
St u d y Sit e R e q uir e m e nt s  ................................................................................................. 3 4  
8. 1  I nv esti g at or/I n v esti g ati o n Sit e S el e cti o n  .................................................................................. 3 4  
8. 2  St u d y Sit e A cti v ati o n  .............................................................................................................. 3 5  
8. 3  R ol e of t h e S p o ns or R e pr es e nt ati v es  ....................................................................................... 3 6  
9.  
S el e cti o n of S u bj e ct s  ........................................................................................................ 3 6  
9. 1  St u d y P o p ul ati o n  .................................................................................................................... 3 6  
9. 2  S u bj e ct E nr oll m e nt  ................................................................................................................. 3 6  
9. 3  I n cl usi o n Crit eri a .................................................................................................................... 3 7  
9. 4  E x cl us i o n Crit eri a ................................................................................................................... 3 7  
1 0.  
St u d y Pr o c e d ur e s  .......................................................................................................... 3 8  
1 0. 1  S c h e d ul e of E v e nts  ................................................................................................................. 3 8  
1 0. 2  D at a C oll e cti o n  ...................................................................................................................... 3 8  
1 0. 3  S c h e d ul e d Visit Wi n d o w s  ........................................................................................................ 4 0  
 
1 0. 5  S u bj e ct C o n s e nt  ..................................................................................................................... 4 1  
1 0. 6  E nr oll m e nt  ............................................................................................................................. 4 2  
1 0. 7  Pr e -Pr o c e d ur e  S cr e e ni n g  ........................................................................................................ 4 3  
1 0. 8  B a s eli n e ................................................................................................................................  4 3  
1 0. 9  D e vi c e Tri al  ........................................................................................................................... 4 4  
1 0. 1 0  
I m a gi n g ......................................................................................................................... 4 4  
1 0. 1 1  
D e vi c e Tri al L e a d E x pl a nt  ................................................................................................ 4 4  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 of 1 1 7   
 
 
 
 
 
1 0. 1 2  
I n c e pti v I m pl a nt ............................................................................................................. 4 4  
1 0. 1 3  
D e vi c e A cti v ati o n  ............................................................................................................ 4 5  
 
 
1 0. 1 5  
R a n d o miz ati o n a n d I n -Cli ni c T esti n g  ................................................................................ 4 5  
1 0. 1 5. 1  
S et -u p a n d T esti n g  .......................................................................................................... 4 6  
1 0. 1 5. 2  
M et h o ds of Assi g ni n g S u bj ects t o Tr e at m e nt Gr o u ps  .................................................... 4 6  
1 0. 1 5. 3  
Bli n di n g  ........................................................................................................................... 4 7  
1 0. 1 5. 4  
Cr oss o v e r......................................................................................................................... 4 7  
1 0. 1 6  
S c h e d ul e d Visits  ............................................................................................................. 4 7  
1 0. 1 6. 1   
3-, 6-, 1 2-, 1 8-, a n d 2 4-M o nt h Visits  ............................................................................... 4 7  
1 0. 1 7  
P h o n e C alls  .................................................................................................................... 4 8  
1 0. 1 8  
U ns c h e d ul e d Visits  .......................................................................................................... 4 8  
1 0. 1 9  
D e vi c e I nt err o g ati o n  ....................................................................................................... 4 8  
1 0. 2 0  
S yst e m M o difi c ati o n  ........................................................................................................ 4 9  
1 0. 2 1  
Ass ess m e nt of Effi c a c y  .................................................................................................... 4 9  
1 0. 2 1. 1  
O v ersti m ul ati o n S e ns ati o n  .............................................................................................. 4 9  
 
 
1 0. 2 1. 3 
Vis u al A n al o g u e Sc al e  ..................................................................................................... 4 9  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 of 1 1 7   
 
 
 
 
 
 
 
 
 
1 0. 2 2  
Ass ess m e nt of S af et y  ...................................................................................................... 5 1  
1 0. 2 3  
R e c or di n g D at a  ............................................................................................................... 5 1  
1 0. 2 4  
D e vi ati o n H a n dli n g  ......................................................................................................... 5 3  
1 0. 2 5  
S u bj e ct E xit, Wit h dr a w al or Dis c o nti n u ati o n  ...................................................................... 5 3  
1 0. 2 5. 1  
St u dy Exit ......................................................................................................................... 5 3  
1 0. 2 5. 2  
St u dy C o m pl et e d  ............................................................................................................. 5 4  
1 0. 2 5. 3  
L ost t o F oll o w-u p  ............................................................................................................ 5 4  
1 1.  
Ri s k s a n d B e n efit s  ........................................................................................................ 5 4  
1 1. 1  P ot e nti al Ris ks  ....................................................................................................................... 5 4  
1 1. 2  F or es e e a bl e Ris ks  .................................................................................................................. 5 5  
1 1. 2. 1  
S C S A dv ers e Ev e nts S u m m ar y  ............................................................................................. 5 5  
1 1. 2. 2  
D evic e/ S oft w ar e D efici e nci es Ris ks  .................................................................................... 5 5  
1 1. 2. 3  
R a di o gr a p hic Risks  .............................................................................................................. 5 6  
1 1. 3  Ris k Mi ni miz ati o n  ................................................................................................................... 5 6  
1 1. 4  P ot e nti al B e n efits  ................................................................................................................... 5 6  
1 1. 5  Ris k- B e n efit R ati o n al e  ............................................................................................................ 5 7  
1 2.  
A d v er s e E v e nt s a n d D e vi c e D efi ci e n ci e s  ...................................................................... 5 7  
1 2. 1  A d v ers e E v e nts  ...................................................................................................................... 5 7  
1 2. 2  D e vi c e D efi ci e n c y  ................................................................................................................... 5 8  
1 2. 3  Pr o c e ssi n g U p d at es a n d R e s ol uti o n  ......................................................................................... 5 8  
1 2. 4  D efi niti o ns/ Cl a ssifi c ati o ns ....................................................................................................... 5 8  
1 2. 5  R e p orti n g of A d v ers e E v e nt s a n d D e vi c e D efi ci e n ci es  ............................................................... 6 3  
1 2. 5. 1  
A dv ers e E v e nt a n d D evic e D efici e nc y Cl assific ati o n  ........................................................... 6 3  
1 2. 5. 2  
A dv ers e E v e nt a n d D evic e D efici e nc y  R e p orti n g R e q uir e m e nts  ........................................ 6 4  
1 2. 6  S u bj e ct D e at h  ........................................................................................................................ 6 7  
1 2. 7  Pr o d u ct C o m pl ai nt R e p orti n g  .................................................................................................. 6 7  
1 3.  
C o m mitt e e s a n d Or g a ni z ati o n s  .................................................................................... 6 8  
1 3. 1  Cli ni c al R es e ar c h Or g a niz ati o n ( C R O)  ...................................................................................... 6 8  
1 3. 2  D at a M o nit ori n g C o m mitt e e ( D M C)  .......................................................................................... 6 8  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 of 1 1 7   
 
 
 
 
 
1 4.  
St ati sti c al D e si g n a n d M et h o d s  .................................................................................... 6 8  
1 4. 1  G e n er al As p e cts of A n al ysis  .................................................................................................... 6 8  
1 4. 1. 1  
A n al ysis S ets  ........................................................................................................................ 6 9  
1 4. 1. 2  
H a n dli n g Missi n g D at a  ........................................................................................................ 6 9  
1 4. 1 . 3 
I nv esti g ati o n Sit e P o oli n g .................................................................................................... 6 9  
1 4. 1. 4  
Dis p ositi o n of S u bj ects  ........................................................................................................ 7 0  
1 4. 1. 5  
D e m o gr a p hics a n d Ot h er B as eli n e C h ar act eristics  ............................................................. 7 0  
1 4. 1. 6  
Ot h er C h ar act eristics  .......................................................................................................... 7 0  
1 4. 1 . 7 
A dj usti n g f or M ulti pl e C o m p aris o ns  ................................................................................... 7 0  
1 4. 2  A n al ysis E x e c uti o n  ................................................................................................................. 7 0  
1 4. 3  I nt eri m A n al ysi s ..................................................................................................................... 7 0  
1 4. 4  Pri m ar y  O bj e cti v e  ................................................................................................................... 7 0  
1 4. 5  S e c o n d ar y O bj e cti v es  ............................................................................................................. 7 2  
1 4. 5. 1  
S ec o n d ar y O bj ecti v e 1: O v er all R es p o n d er R at es  ............................................................... 7 2  
1 4. 5. 2  
S ec o n d ar y O bj ecti v e 2: P ai n -S p ecific R es p o n d er R at es  ...................................................... 7 3  
 
1 4. 7  S af et y Ass es s m e nt  ................................................................................................................. 7 6  
 
1 4 . 9 Mi ni miz ati o n of Bi a s  ............................................................................................................... 7 7  
1 5.  
Et hi c s  ............................................................................................................................  7 7  
1 5. 1  St at e m e nt(s) of C o m pli a n c e .................................................................................................... 7 7  
1 6 . 
St u d y A d mi ni str ati o n  .................................................................................................... 7 9  
1 6. 1  M o nit ori n g  ............................................................................................................................. 7 9  
1 6. 1. 1  
M o nit ori n g Visits  ................................................................................................................. 7 9  
1 6. 2  D at a M a n a g e m e nt  .................................................................................................................. 7 9  
1 6. 3  Dir e ct A c c ess t o S o ur c e D at a/ D o c u m e nts  ................................................................................ 8 0  
1 6. 4  C o nfi d e nti alit y ........................................................................................................................ 8 0  
1 6. 5  Li a bilit y ................................................................................................................................ . 8 0  
1 6. 5. 1  
I ns ur a nc e ( A ustr ali a) ........................................................................................................... 8 0  
1 6. 6  CI P A m e n d m e nts  ................................................................................................................... 8 0  
1 6. 7  R e c or d R et e nti o n  ................................................................................................................... 8 1  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 of 1 1 7   
 
 
 
 
 
1 6. 7. 1  
I nv esti g at or R ec or ds ........................................................................................................... 8 1  
1 6. 7. 2  
S p o ns or R ec or ds  ................................................................................................................. 8 2  
1 6. 8  R e p orti n g R e q uir e m e nts  ......................................................................................................... 8 3  
1 6. 8. 1  
I nv esti g at or R e p orts ............................................................................................................ 8 3  
1 6. 8. 2  
S p o ns or R e p orts  .................................................................................................................. 8 4  
1 6. 9  P u bli c ati o n a n d U s e of I nf or m ati o n  ......................................................................................... 8 6  
1 6. 9. 1  
P u blic ati o n C o m mitt e e  ....................................................................................................... 8 6  
1 6. 9. 2  
M a n a g e m e nt of Pri m ar y, S ec o n d ary, a n d A ncill ary P u blic ati o ns  ....................................... 8 7  
1 6. 9. 3  
Crit eri a f or D et er mi ni n g A ut h ors hi p  ................................................................................... 8 7  
1 6. 9. 4  
Tr a ns p ar e nc y  ....................................................................................................................... 8 8  
1 6. 1 0  
S us p e nsi o n or E arl y T er mi n ati o n  ...................................................................................... 8 8  
1 6. 1 0. 1  
Pl a n n e d St u dy Cl os ur e  .................................................................................................... 8 8  
1 6. 1 0. 2  
E arl y T er mi n ati o n or S us p e nsi o n  .................................................................................... 8 8  
1 6. 1 0. 3  
Pr oc e d ur es f or T er mi n ati o n or S us p e nsi o n  .................................................................... 8 9  
1 7.  
R ef er e n c e s  ....................................................................................................................  9 0  
1 8.  
A p p e n di c e s  ...................................................................................................................  9 3  
1 8. 1  A p p e n di x A: F or es e e a bl e A d v ers e E v e nts  ................................................................................. 9 3  
1 8. 2  A p p e n di x B: P arti ci p ati n g I n v esti g at ors a n d I nstit uti o n s  ........................................................... 9 7  
1 9.  
V er si o n Hi st or y  ............................................................................................................. 9 8  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 of 1 1 7   
 
 
 
 
 
2.  Gl o s s ar y  
T a bl e 1 : Gl o s s ar y 
T er m  
D efi niti o n  
A E  
A dv ers e E v e nt  
A D E  
A dv ers e D e vic e Eff ect  
A S A D E  
A ntici p at e d S eri o us A dv ers e D e vic e Eff ect  
C V  
C urric ul u m Vit a e  
C F R  
C o d e of F e d er al R e g ul ati o n  
CI P  
Cli nic al I nv esti g ati o n Pl a n  
C R O  
Cli nic al R es e arc h Or g a niz ati o n  
C R F  
C as e R e p ort F or m  
C T A  
Cli nic al Tri al A gr e e m e nt  
D D  
D evic e D efici e ncy  
D M C  
D at a M o nit ori n g C o m mitt e e  
D o H  
D ecl ar ati o n of H elsi n ki  
D TL  
D el e g at e d T as k List  
E C  
Et hics C o m mitt e e  
e C R F  
El ectr o nic C as e R e p ort F or m  
E C A Ps  
E v ok e C o m p o u n d Acti o n P ot e nti als  
 
 
F AL  
F or es e e a bl e A dv ers e Ev e nt List  
F D  
Fi n a nci al Discl os ur e  
G C P  
G o o d Cli nic al Pr actic e  
I B 
I nv esti g at or’s Br oc h ur e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0  of 1 1 7  
 
 
 
 
 
T er m  
D efi niti o n  
I C 
I nf or m e d C o ns e nt 
I C F 
I nf or m e d C o ns e nt F or m 
I F U 
I nstr ucti o ns F or Us e 
I N S 
I m pl a nt a bl e N e ur osti m ul at or 
 
 
 
 
N S R  
N o n -Si g nific a nt Ris k  
 
 
P HI  
Pr ot ect e d H e alt h I nf or m ati o n  
 
 
 
 
 
 
R A  
R e g ul at ory A ut h orit y  
R C  
R ec h ar g e a bl e  
S F  
S h ort F or m  
S A E  
S eri o us A dv ers e Ev e nt  
S A P  
St atistic al A n alysis Pl a n  
S C S  
S pi n al C or d Si m ul ati o n  
S SI  
Si g nific a nt S af et y Iss u e  
S A D E  
S eri o us A dv ers e D e vic e Eff ect  
T G A  
T h er a p e utic G o o ds A d mi nistr ati o n  
U A E  
 
U n a v oi d a bl e A dv ers e E v e nt  
U S M  
Ur g e nt S af et y M e as ur e  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1  of 1 1 7  
 
 
 
 
 
T er m  
D efi niti o n  
 
 
U S A D E  
U n a ntici p at e d S eri o us A dv ers e D evic e Eff ect  
V A S  
Vis u al A n al o g u e  Sc al e  
 
3.  S y n o p si s  
T a bl e 2 : S y n o p si s 
Titl e  
E v al u ati o n of L o n g -t er m P ati e nt Ex p eri e nc e wit h a 
M e dtr o nic Cl os e d -L o o p S CS S yst e m (Cl os e d -L o o p S C S 
st u dy) 
Cli nic al St u dy Ty p e  
Pr os p ectiv e , m ulti -c e nt er, r a n d o miz e d, si n gl e-bli n d, 
i nv esti g ati o n al, f e asi bilit y st u dy 
Pr o d uct N a m e  
P ai n R C s yst e m wit h I nc e pti v™ I N S r ef err e d t o as I nc e pti v 
i n t his st u dy 
S p o ns or / F u n di n g S o urc e   
M e dtr o nic  N e ur o m o d ul ati o n   
 
 
L oc al S p o ns or 
M e dtr o nic A ustr al asi a Pt y Lt d.  
 
 
I n dic ati o n U n d er Inv esti g ati o n  
T h e n ext g e n er ati o n spi n al cor d sti m ul ator , I nc e ptiv, is 
i n dic at e d t o ai d i n t h e m a n a g e m e nt of c hr o nic, i ntr act a bl e 
p ai n of t h e tr u n k a n d/ or li m bs. P ati e nts  wit h  st a bl e 
i ntr act a bl e A n gi n a P ect oris or P eri p h er al V asc ul ar Dis e as e 
of F o nt ai n e St a g e III or hi g h er  will b e excl u d e d fr o m t h e 
st u dy.  
I nv esti g ati o n P ur p os e 
C h ar act eriz e  t h e effic acy of t h e n ext g e n er ati o n, 
r ec h ar g e a bl e, s pi n al c or d sti m ul at or 
Pr o d uct St at us  
T h e I nc e ptiv s pi n al c or d sti m ul at or is i nv esti g ati o n al 
Pri m ar y O bj ectiv e  
T o d e m o nstr at e t h at t h e pr o p orti o n of l o w-b ack a n d / or 
l e g p ai n s u bj ects h a vi n g  a r e d ucti o n i n ov ersti m ul ati o n 
s e ns ati o n wit h N e ur o S e ns e O n c o m p ar e d t o N e ur o S e ns e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 2  of 1 1 7  
 
 
 
 
 
Off , at t h e r a n d o miz ati o n a n d i n-cli nic t esti n g visit, 
exc e e ds a p erf or m a nc e g o al of 5 0 %.  
S ec o n d ar y O bj ecti v e s 
1.  T o c h ar act eriz e t h e effic ac y of s pi n al c or d sti m ul ati o n 
(S C S ) t h er a py f or t h e tr e at m e nt of ov er all p ai n i n l o w-
b ac k a n d / or l e g p ai n  s u bj ects by e v al u ati n g t h e 
effic ac y r es p o n d er r at e. T h e effic ac y r es p o n d er r at e is 
d efi n e d as t h e p erc e nt a g e of  l o w-b ac k a n d/ or l e g p ai n  
i m pl a nt e d s u bj ects w h o ex p eri e nc e at l e ast a 5 0 % 
i m pr ov e m e nt i n o v er all p ai n, as m e as ur e d by t h e 
Vis u al A n al o g u e  Sc al e ( V A S), f r o m B as eli n e t o t h e 3-
M o nt h Visit.  
2.  T o c h ar act eriz e t h e effic ac y r es p o n d er r at e of  l o w-
b ac k p ai n a n d  l e g p ai n  i n l o w-b ac k a n d / or l e g p ai n 
s u bj ects, as m e as ur e d by t h e p ai n -s p ecific V A S, fr o m 
B as eli n e t o t h e 3 -M o nt h Visit. T h e l o w -b ac k 
r es p o n d er r at e will b e c h ar act eriz e d f or s u bj ects wit h 
b as eli n e b ac k V A S ≥ 6 0 m m , a n d t h e l e g r es p o n d er 
r at e will b e c h ar act eriz e d f or s u bj ects wit h b as eli n e 
l e g V A S ≥ 6 0 m m . 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 3  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
 
  
St u dy D esi g n  
Pr os p ectiv e , m ulti-c e nt er, r a n d o miz e d, si n gl e-bli n d, 
i nv esti g ati o n al, f e asi bilit y st u dy. Eli gi bl e p ati e nts will b e 
c o ns e nt e d a n d e nr oll e d, u n d er g o a psyc h ol o gic al 
e v al u ati o n, h av e a n x -r a y or M RI, as n e e d e d, b e ev al u at e d 
f or b as eli n e ass ess m e nts, u n d er g o a n S C S tri al a n d if 
s ucc essf ul, u n d er g o t h e i m pl a nt of a p er m a n e nt I N S. 
F oll o wi n g i m pl a nt, s u bj ects will h a v e t h eir S C S d evic e  
s etti n gs o pti miz e d  f or t h e N e ur o S e nse f e at ur e.   F oll o wi n g 
d e vic e o pti miz ati o n, s u bj ects will b e r a n d o miz e d  t o a 
s e q u e nc e of N e ur o S e ns e On a n d N e ur o S e ns e O ff f or i n-
cli nic t esti n g.  S u bj ects will  t h e n c o nti n u e b ein g f oll o w e d 
p eri o dic all y  f or a t ot al st u dy d ur ati o n of u p t o  2 4 -m o nt hs.  
R a n d o miz ati o n  
1: 1 r a n d o miz ati o n  (o n e of t h e t w o s e q u e nc es ): N e ur o 
S e ns e O n f oll o w e d by N e ur o S e ns e Off or N e ur o S e ns e Off 
f oll o w e d by N e ur o S e ns e O n  
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 4  of 1 1 7  
 
 
 
 
 
 
 
I ncl usi o n/ Excl usi o n Crit eri a 
I ncl usi o n Crit eri a:   
1.  1 8 y e ars of a g e or ol d er   
2.  C a n di d at e  is u n d er g oi n g  M e dtr o nic S C S d e vic e  
tri al f or c hr o nic, i ntr act a bl e p ai n of t h e tr u n k 
a n d/ or li m bs  d u e t o F ail e d B ac k S ur g ery  
Sy n dr o m e ( F B S S), C o m pl ex R e gi o n al P ai n 
Sy n dr o m e ( C R P S), or ot h er c hr o nic n e ur o p at hic 
p ai n wit h o ut hist or y of s ur gic al i nt er v e nti o ns.  
N ot e:  T h e s p o ns or r ec o m m e n ds n ot e nr olli n g 
p ati e nts wit h c hr o nic p ai n d u e t o c o n diti o ns t h at 
d o n ot h av e a d e q u at e evi d e nc e t o s u p p ort t h e us e 
of S C S ( e. g., p ost -h er p etic n e ur al gi a, f oc al C R PS 
etc.)  
3.  If b ei n g tr e at e d f or l o w-b ack a n d / or l e g p ai n,  
o  t h e b as eli n e ov er all ^ V A S is ≥ 6 0 m m  a n d   
o  b as eli n e b ac k a n d/ or  l e g p ai n V A S is ≥6 0 
m m.    
^ a v er a g e o v er all p ai n i n t h e b ac k a n d/ or 
l e g i n t h e 7 2 h o urs pri or t o t h e b as eli n e 
visit, m e as ur e d usi n g V A S.   
4.  If b ei n g tr e at e d f or u p p er li m b p ai n – b as eli n e 
V A S is ≥ 6 0 m m f or u p p er li m b p ai n  
5.  O n st a bl e ( n o c h a n g e i n d os e, r o ut e, or 
fr e q u e nc y) pr escri b e d  p ai n m e dic ati o ns  b ei n g 
us e d f or b ac k a n d / or l e g p ai n or u p p er li m b p ai n, 
as d et er mi n e d by t h e i nv esti g at or, f or at l e ast 2 8 
d a ys pri or t o  devic e  tri al 
6.  Willi n g a n d a bl e t o pr o vi d e si g n e d a n d d at e d 
inf or m e d c o ns e nt  
7.  Willi n g a n d a bl e t o c o m pl y wit h all st u dy 
pr oc e d ur es a n d visits  
* T h e s p o n s o r st r o n gl y r e c o m m e n d s o nl y e n r olli n g 
p ati e nt s c a p a bl e of c o m p r e h e n di n g a n d c o n s e nti n g 
i n E n gli s h. 
 
E xcl usi o n Crit eri a:  
1.  I n dic at e d f or a n S C S d evic e t o tr e at st a bl e 
i ntr act a bl e A n gi n a P ect oris, P eri p h er al V asc ul ar 
Dis e as e of F o nt ai n e St a g e III or hi g h er , or Di a b etic 
P eri p h er al N e ur o p at hy  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 5  of 1 1 7  
 
 
 
 
 
2.  Pr evi o usly tri al e d or i m pl a nt e d wit h s pi n al c or d 
sti m ul at or, p eri p h er al or v a g us n er v e sti m ul at or, 
d e e p br ai n sti m ul at or or a n i m pl a nt a bl e 
i ntr at h ec al dr u g d eliv ery syst e m 
3.  C urr e ntl y p artici p ati n g, or pl a ns t o p artici p at e, i n 
a n ot h er i nv esti g ati o n al st u dy u nl ess writt e n 
a p pr o v al is pr ovi d e d by t h e M e dtr o nic st u dy t e a m  
4.  M aj or ps yc hi atric c o m or bi dit y or ot h er 
pr o gr ess iv e dis e as es t h at m a y c o nf o u n d st u dy 
r es ults, as d et er mi n e d by t h e I nv esti g at or 
5.  S eri o us dr u g -r el at e d b e h avi or al iss u es ( e. g., 
alc o h ol d e p e n d e ncy, ill e g al s u bst a nc e a b us e), as 
d et er mi n e d by t h e  I nv esti g at or 
N ot e: T h e S p o ns or r ec o m m e n ds excl u di n g 
p ati e nts o n  ≥1 0 0 M M E of o pi oi ds/ d ay.  
6.  Pr e g n a nt or pl a n ni n g o n b ec o mi n g pr e g n a nt (if 
f e m al e a n d s ex u all y activ e, s u bj ect m ust b e usi n g 
a r eli a bl e f or m of birt h c o ntr ol, b e s ur gic all y 
st eril e, or b e at l e ast 2 y e ars p ost-m e n o p a us al)  
7.  B e i nv ol v e d  i n a n i nj ur y cl ai m or u n d er c urr e nt  
liti g ati o n 
N ot e: t his i ncl u d es p ati e nts t h at ar e t h e 
b e n efici ar y of a s ucc essf ul i nj ur y cl ai m.  
St u dy Pr oc e d ur es a n d Ass ess m e nts  
St u d y Visits  
•  
E nr oll m e nt/ B as eli n e  
•  
D evic e  Tri al  
•  
Tri al L e a d Ex pl a nt  
•  
S C S  I m pl a nt 
•  
D evic e  Acti v ati o n  
•  
D evic e  O pti miz ati o n  ( u p t o o n e -m o nt h)  
•  
R a n d o miz ati o n  a n d  I n-Cli nic T esti n g  
•  
Visits  ( 3-M o nt h,  6-M o nt h,  1 2 -M o nt h,  1 8 -M o nt h , 
a n d  2 4 -M o nt h)  
 
E nr oll m e nt/ B as eli n e:  
S u bj ects ar e c o nsi d er e d e nr oll e d at t h e ti m e t h e st u dy -
s p ecific i nf or m e d c o ns e nt f or m is si g n e d.  S u bj ects i n 
c o m pli a nc e wit h i ncl usi o n/ excl usi o n crit eri a will b e 
eli gi bl e t o p artici p at e.   V A S sc or es  f or o v er all, l o w -b ack 
a n d l e g O R u p p er  li m b a n d n ec k p ai n will b e c oll ect e d.  
S u bj ects t h at m e et i ncl usi o n crit eri a  a n d n o n e of t h e  
excl usi o n crit eri a  wil l b e ask e d a b o ut t h eir p ai n a n d 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 6  of 1 1 7  
 
 
 
 
 
m e dic al hist ory, sc h e d ul e d f or a d e vic e tri al a n d c o m pl et e 
t h e r e q uir e d ass ess m e nts. 
 
D e vic e Tri al  ( ≤ 2 8  d a ys p ost  B as eli n e  ass ess m e nt):  
S u bj ects will b e i m pl a nt e d wit h t w o p erc ut a n e o us l e a ds  
a n d  sti m ul ati o n will b e a p pli e d usi n g a wir el ess ext er n al 
n e ur osti m ul at or .  T h e  tri al-p h as e is n ot  t o exc e e d  1 0 d a ys . 
 
Tri al L e a d E x pl a nt:  L e a ds will b e ex pl a nt e d at t h e e n d of 
t h e tri al p eri o d.  S elf -r e p ort e d p ai n r eli ef will b e c oll ect e d.  
S u bj ects w h o h av e a 5 0 % or gr e at er r e d ucti o n i n p ai n will 
g o o nt o a p er m a n e nt  S C S  syst e m i m pl a nt i n t h e st u dy. 
 
S C S I m pl a nt:  A n  I nc e pti v d e vic e will b e  i m pl a nt e d a n d 
c o n n ect e d t o t h e l e a d(s).  
 
D e vic e Acti v ati o n:  T h e d evic e will b e t ur n e d o n a n d  t h e 
o pti miz ati o n p eri o d will b e gi n.   
  
 
 
 
 
 
 
  
R a n d o miz ati o n a n d I n-cli nic T esti n g: A p pr oxi m at el y  1-
M o nt h p ost D e vic e Acti v ati o n, s u bj ects will u n d er g o 
r a n d o miz ati o n a n d i n-cli nic t esti n g.  S u bj ects will b e 
r a n d o miz e d t o o n e of t h e t w o s e q u e nc es: N e ur o S e ns e 
O n f oll o w e d by N e ur o S e ns e Off or N e ur o S e ns e Off 
f oll o w e d by N e ur o S e ns e O n.  S u bj ect s will b e bli n d e d t o 
t h e s etti n gs t est e d. I n e ac h s etti n g, s u bj ects will p erf or m 
a s eri es of 3- 5 acti viti es,
 w hic h 
ar e d esi g n e d t o i n d uc e o v ersti m ul ati o n.    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
S u bj ects will b e ask e d t o r at e t h e i nt e nsity  of t h e 
o v ersti m ul ati o n s e ns ati o n t h e y ex p eri e nc e d w hil e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 7  of 1 1 7  
 
 
 
 
 
p erf or mi n g t h e activit y usi n g a 5 -p oi nt Li k ert sc al e aft er 
e ac h activity.  S u bj ects will b e as k e d w hic h s etti n g t h ey 
pr ef err e d f oll o wi n g t h e t esti n g of b ot h s etti n gs.    
 
It is str o n gl y r ec o m m e n d e d t o pr o gr a m t h e S C S d evic e 
wit h N e ur o S e ns e O n f or t h e d ur ati o n of t h e st u dy.   
 
Visits ( 3 -, 6-, 1 2-, 1 8-, a n d 2 4 - Mo nt h s p ost D e vic e 
Acti v ati o n ): F oll o wi n g i n-cli nic t esti n g, s u bj ects will c o m e 
i n f or r e g ul ar visits a n d effic ac y a n d s af ety of t h e t h er a py 
will b e ass ess e d .  U nsc h e d ul e d visits m a y  occ ur as 
n ec ess ary.  
 
P h o n e C alls:  S u bj ects will b e c all e d e v er y w e e k st arti n g 
aft er D evic e Activ ati o n  t hr o u g h t h e 3-M o nt h Visit a n d 
m o nt hl y t h er e aft er wit h a n exc e pti o n f or t h e w e e ks or 
m o nt hs w h e n t h e s u bj ect h as a st u dy r e q uir e d visit. If t h e 
s u bj ect r e p orts b ei n g U ns atisfi e d wit h t h e t h er a py, as 
d et er mi n e d by t h e p h o n e c all, t h e s u bj ect m ay b e br o u g ht  
i n f or a n U nsc h e d ul e d visit f or f urt h er t h er a py 
o pti miz ati o n. Alt er n ativ el y, if t h e p ai n sc or e r e p ort e d by  
t h e s u bj ect d uri n g t h e p h o n e c all is ≥4, or if t h ey r e p ort 
ex p eri e nci n g  ov ersti m ul ati o n  t h e sit e s h o ul d c o nt act 
S p o ns or R e pr es e nt ativ e  t o f urt h er ev al u at e t h e n e e d f or 
th er a py o pti miz ati o n; t h e Sp o ns or  r e pr es e nt ativ e m ay 
c o nt act t h e s u bj ect t o tr o u bl es h o ot o v er t h e p h o n e pri or 
t o sc h e d uli n g a n i n-cli nic visit.  
 
S af et y Ass ess m e nts  
T h e f oll o wi n g A dv ers e Ev e nts will b e c oll ect e d : d e vic e -
r el at e d, pr oc e d ur e-r el at e d, t h er a py-r el at e d, a n d s eri o us.  
All d e vic e d efici e nci es will b e c oll ect e d.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 8  of 1 1 7  
 
 
 
 
 
St atistics  
F or t h e pri m ary o bj ecti v e, it is hy p ot h esiz e d t h at t h e  
pr o p orti o n of l o w-b ack a n d / or l e g p ai n  s u bj ects ( p) h avi n g  
a r e d ucti o n i n ov ersti m ul ati o n s e ns ati o n d uri n g N e ur o 
S e ns e O n c o m p ar e d t o N e ur o S e ns e Off p eri o d exc e e ds a 
p erf or m a nc e g o al of 5 0 %.  
 
H 0: p ≤ 5 0 % 
H A : p > 5 0 % 
 
T h e pr o p orti o n of l o w-b ac k a n d / or l e g p ai n s u bj ects wit h 
a r e d ucti o n i n ov ersti m ul ati o n s e ns ati o n d uri n g N e ur o 
S e ns e O n  c o m p ar e d t o N e ur o S e ns e Off  p eri o d will b e 
c alc ul at e d, wit h a o n e-si d e d 9 7. 5 % c o nfi d e nc e l o w er 
b o u n d. T his pr o p orti o n will b e t est e d a g ai nst 5 0 % usi n g a 
bi n o mi al ex act t est. T h e c o nfi d e nc e l o w er b o u n d n e e ds t o 
b e gr e at er t h a n 5 0 %, or e q ui v al e ntl y, t h e p -v al u e m ust b e 
l ess t h a n 0. 0 2 5 t o r ej ect t h e n ull hy p ot h esis.  
 
F or t h e pri m ary o bj ecti v e, P A S S 2 0 2 0 T ests f or O n e 
Pr o p orti o n w as us e d t o c alc ul at e t h e s a m pl e siz e, wit h a 
n ull pr o p orti o n of 5 0 %, a n d a n alt er n ativ e pr o p orti o n of 
8 0 %; 2 8 s u bj ects ar e n e e d e d t o ac hi e v e m or e t h a n 9 0 % 
p o w e r wit h a o n e-si d e d t est a n d  al p h a = 0. 0 2 5. T his is a 
s u bs et of t h e t ot al d evic e i m pl a nt e d  l o w-b ack a n d / or l e g 
p ai n s u bj ects.  
 
 
 
 
 
 
 
 
 
T h e first s ec o n d ar y o bj ectiv e is t o c h ar act eriz e t h e ov er all 
r es p o n d er r at e, w hic h is d efi n e d as t h e p erc e nt a g e of 
l o w-b ack a n d / or l e g p ai n i m pl a nt e d s u bj ects w h o 
ex p eri e nc e at l e ast a 5 0 % i m pr ov e m e nt i n o v er all p a i n, as 
m e as ur e d by t h e V A S, fr o m B as eli n e t o t h e 3 -M o nt h Visit.   
T h e ot h er s ec o n d ar y o bj ecti v e is t o c h ar act eriz e t h e 
r es p o n d er r at e s e p ar at el y f or l o w-b ac k  or l e g p ai n , as 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 9  of 1 1 7  
 
 
 
 
 
m e as ur e d by t h e  p ai n -s p ecific V A S , fr o m B as eli n e t o t h e 
3- M o nt h Visit . T h e l o w -b ack  r es p o n d er r at e will b e 
c h ar act eriz e d f or s u bj ects wit h b as eli n e b ac k V A S ≥ 6 0 
m m , a n d t h e l e g r es p o n d er r at e will b e c h ar act eriz e d f or 
s u bj ects wit h b as eli n e l e g V A S ≥ 6 0 m m.  
 
U p t o 4 5 i m pl a nt e d s u bj ects wit h l o w-b ack a n d / or l e g 
p ai n ar e d esir e d t o c h ar act eriz e t h e r es p o n d er r at es at 
t h e 3-M o nt h Visit.  T h e pr o p orti o n of r es p o n d ers will b e 
pr es e nt e d f or b ot h s ec o n d ar y o bj ectiv es, wit h 9 5 % 
c o nfi d e nc e i nt erv als. I nf or m ati o n fr o m s u bj ects wit h  d at a 
a v ail a bl e at b as eli n e a n d t h e 3 - Mo nt h Visit  will b e us e d 
f or t h es e o bj ecti v es. 
 
 
 
 
 
 
 
 
A dv ers e ev e nts a n d d e vic e d efici e nci es will b e 
s u m m ariz e d usi n g t a bl es dis pl a yi n g t h e fr e q u e nc y a n d 
p erc e nt a g e of ev e nt , as w ell as n u m b er of s u bj ects 
ex p eri e nci n g e v e nt . A dv ers e ev e nts will b e s u m m ariz e d 
by s eri o us n ess as w ell.  
 
4.  I ntr o d u cti o n  
4. 1  B a c k gr o u n d  
S pi n al c or d sti m ul ati o n ( S CS) is a t h er a py f or t h e tr e at m e nt of c hr o nic p ai n t h at r eli es o n t h e a p plic ati o n 
of mil d el ectric al sti m ul ati o n  d eli v er e d t o t h e d ors al c ol u m n fi b ers of t h e s pi n al c or d vi a a l e a d or l e a ds 
im pl a nt e d i n t h e e pi d ur al s p ac e.  T h e el ectric al sti m ul ati o n us e d i n t h e t h er a py is pr o vi d e d by a n 
ext er n al n e ur osti m ul at o r d uri n g a scr e e ni n g tri al, w hic h is c o n d uct e d t o d et er mi n e if S C S c o ul d w or k 
l o n g-t er m f or a p ati e nt.  If a p ati e nt h as a s ucc essf ul scr e e ni n g tri al (t y pic all y d efi n e d as ≥ 5 0 % p ai n 
r eli ef), t h e n a p er m a n e nt i m pl a nt a bl e p uls e g e n er at or (I P G) w o ul d b e i m pl a nt e d i n t h e p ati e nt a n d 
pr o vi d e t h e el ectric al sti m ul ati o n t o t h e d ors al c ol u m n  vi a t h e e pi d ur all y pl ac e d l e a ds.    
M e dtr o nic r ec eiv e d U S F D A a p pr o v al f or its first S C S I P G i n 1 9 8 4.  I n t h e n e arl y 4 0 y e ars si nc e t h at first 
a p pr o v al ot h er c o m p a ni es h a v e e nt er e d t his s p ac e , n u m er o us cli nic al st u di es h av e b e e n c o n d uct e d a n d 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 0  of 1 1 7  
 
 
 
 
 
r e al-w orl d d at a s ets c oll ect e d d e m o nstr ati n g t h e effic ac y a n d eff ectiv e n ess of S CS  i n all e vi ati n g c hr o nic 
p ai n , r efr act or y t o c o nv e nti o n al tr e at m e nt.  I n r ec e nt y e ars, as k n o wl e d g e h as gr o w n, att e nti o n h as 
s hift e d t o w ar ds u n d erst a n di n g t h e i m p act of diff er e nt sti m ul ati o n p ar a m et ers t o f urt h er i m pr ov e 
p ati e nt o utc o m es.    
A v ari et y of sti m ul ati o n p ar a di g ms, i nv olvi n g diff er e nt p uls e r at e, d ut y c ycl e, l e a d  l oc ati o n a n d a ut o m atic 
vs. m a n u al pr o gr a m mi n g, h a v e b e e n s ucc essf ull y tri al e d i n t his p ati e nt p o p ul ati o n i ncl u di n g: Hi g h 
fr e q u e nc y ( ≤1 0 k Hz) sti m ul ati o n1, b urst2, 3, d ors al r o ot g a n gli o n sti m ul ati o n4,  c o m bi n ati o n of hi g h 
fr e q u e nc y a n d l o w fr e q u e nc y5, diff er e nti al t ar g et e d m ulti pl exi n g ( D T M)6 a n d cl os e d l o o p S C S ( e. g., 
p ositi o n -a d a pti v e) 7 – 9. T h es e t h er a py o pti o ns ar e als o c h ar act eriz e d as p ar est h esi a-b as e d 1, 1 0 or 
p ar est h esi a -fr e e1, 8, d e p e n di n g o n t h e m o d e of pai n -r eli ef. R es p o n d er r at es ( ≥5 0 % p ai n r eli ef) of o v er 
8 0 % h av e b e e n r e p ort e d i n e ac h of t h es e st u di es; t h e p ai n r eli ef w as als o f o u n d t o b e s ust ai n e d l o n g -
t er m.1 1, 1 2, 2, 8 I n a d diti o n t o p ai n r eli ef, p ati e nts als o ex p eri e nc e d i m pr o v e m e nts i n q u alit y of lif e, f u ncti o n, 
sl e e p q u alit y a n d r e d ucti o n/ eli mi n ati o n of p ai n m e dic ati o n2, 3. 
W hil e t h e effic ac y of S C S  i n all e vi ati n g c hr o nic p ai n h as b e e n d e m o nstr at e d f or v ari o us i n dic ati o ns, it is 
n ot wit h o ut u n w a nt e d si d e eff ects.   O n e s uc h a dv ers e eff ect, o v ersti m ul ati o n , is t h e f oc us of t his 
i nv esti g ati o n. Ov ersti m ul ati o n occ urs w h e n t h e i nt e nsit y of t h e d eliv er e d sti m ul ati o n r e ac h es a l ev el 
w h er e a p ati e nt m a y ex p eri e nc e disc o mf ort or ev e n p ai n.  T his ev e nt  t y pic ally occ urs w h e n t h e dist a nc e 
b et w e e n t h e s pi n al c or d a n d t h e e pi d ur al l e a d(s) d e cr e as es, w hic h m ay r es ult i n t h e s pi n al c or d r ec eivi n g 
a l ar g er a m o u nt of sti m ul ati o n t h a n d esir e d. 
 
 
Si nc e 2 0 1 1, M e dtr o nic h as utiliz e d A d a pti v e Sti m ™ T ec h n ol o gy t o a d dr ess ov ersti m ul ati o n 9.  
A d a ptiv e Sti m us es a n acc el er o m et er wit hi n t h e I N S t o s e ns e a c h a n g e i n p ositi o n. T h e A d a pti v e Sti m 
f e at ur e all o ws f or c ert ai n t h er a py i nt e nsiti es t o b e s et f or six or s ev e n p ositi o ns, d e p e n di n g o n t h e 
m o d el a p ati e nt h as i m pl a nt e d.  B as e d o n f e e d b ack fr o m t h e  p ati e nt , a h e alt hc ar e pr actiti o n er c a n s et 
t h e d esir e d i nt e nsity, a n d w h e n a p ati e nt c h a n ges p ositi o n i nt o o n e of t h e pr e -s et p ositi o ns, t h e 
i nt e nsit y is a ut o m atic ally a dj ust e d.  T his is a n eff ectiv e f e at ur e t h at b e g a n t o a d dr ess t his t h er a py-
li miti n g iss u e of ov ersti m ul ati o n b ut giv e n its li mit ati o n of o nl y a dj usti n g f or c ert ai n p ositi o ns a n d 
r es p o n di n g o n t h e or d er of s ec o n ds, n ot millis ec o n ds, M e dtr o nic is s e eki n g t o i m pr o v e u p o n t h e f e at ur e 
ai m e d at  a d dr essi n g  ov ersti m ul ati o n
 
 
M e dtr o nic’s  cl os e d-l o o p al g orit h m, us es  t h e e v o k e d c o m p o u n d acti o n p ot e nti al ( E C A P ), w hic h  is t h e 
s pi n al c or d’s p hysi ol o gic al r es p o ns e t o sti m ul ati o n,1 3 t o a dj ust t h e am plit u d e of sti m ul ati o n, if r e q uir e d.  
E C A Ps ar e t h e s u m m e d acti o n p ot e nti als elicit e d fr o m a n er v e or gr o u p of n er v es i n r es p o ns e t o a 
sti m ul us.  P ar k er et al. w er e t h e first t o r e p ort r ec or di n g h u m a n E C A Ps fr o m t h e D ors al C ol u m ns ( D C)  of 
t h e s pi n al c or d usi n g t h e l e a d t h at is us e d t o d eliv er c o nv e nti o n al S C S 1 3.  Pri or t o t his, m ost E C A Ps w er e 
r ec or d e d usi n g i nv asiv e micr o el ectr o d e r ec or di n gs i n a ni m als . Si nc e t h e n, t h e gr o u p h as r e p or t e d 
f urt h er st u di es of s pi n al c or d E C A Ps, wit h v ari o us sti m ul ati o n p ar a m et ers, l e a d l oc ati o ns a n d s p aci n g, 
fr o m b ot h h u m a ns a n d s h e e p1 4, 1 5. 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 1  of 1 1 7  
 
 
 
 
 
 
 
  
R ec or di n g s of s pi n al c or d acti vity i n r es p o ns e t o sti m ul ati o n ty pic all y h a v e  t w o m aj or c o m p o n e nts: t h e 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
 
  
S al u d a t h e n l a u nc h e d t h eir pi v ot al tri al at 2 0  sit es i n t h e U nit e d St at es, t h e E V O K E st u dy, i n 2 0 1 7. EV O K E 
w as a d o u bl e bli n d, r a n d o miz e d c o ntr oll e d st u dy, wit h c o nv e nti o n al ( o p e n l o o p) S C S f or mi n g t h e c o ntr ol 
ar m. O n e h u n dr e d a n d t hirt y -f o ur p ati e nts wit h c hr o nic b ac k or l e g p ai n, V A S sc or e of > = 6 0 m m, 
r efr act or y t o c o nv e nti o n al tr e at m e nt, a n d Os w estr y Dis a bilit y I n d ex of 4 1-8 0, a n d n o pr evi o us 
ex p eri e nc e wit h S C S, w er e e nr oll e d a n d r a n d o miz e d. Ei g ht y -t w o p erc e nt of t h e 1 2 5 p ati e nts t h at 
c o m pl et e d t h e 3- Mo nt h f oll o w -u p ex p eri e nc e d > = 5 0 % p ai n r eli ef c o m p ar e d t o 6 0. 2 % i n t h e o p e n -l o o p 
gr o u p. T h e s af ety pr of il e of t h e t w o-ar ms w as si mil ar. N o a dv ers e e v e nts w er e attri b ut e d t o s e nsi n g 
E C A Ps usi n g cl os e d -l o o p f e e d b ac k sti m ul ati o n. T h es e o utc o m es w er e s ust ai n e d t hr o u g h t h e 1 2 -m o nt h 
a n d 2 4 -m o nt h f oll o w -u ps.  1 8, 1 9 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 2  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 3  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
  
 
 
 
            
4. 2  P ur p o s e  
T h e p ur p os e of t h e Cl os e d -L o o p S C S st u dy is t o f urth er o ur u n d erst a n di n g of cl os e d-l o o p S C S  i n p ati e nts 
i m pl a nt e d wit h t h e I nc ept iv I N S.  T h e Cl os e d -l o o p S C S st u dy is a pr os p ectiv e , m ulti-c e nt er, r a n d o miz e d, 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 4  of 1 1 7  
 
 
 
 
 
si n gl e-bli n d, i nv esti g ati o n al, f e asi bility st u dy. T his is a first -i n-m a n st u dy  si nc e t h e f ull y i m pl a nt a bl e 
I nc e ptiv d e vic e h as n ot b e e n st u di e d i n h u m a ns. T h e st u dy will a dv a nc e o ur k n o wl e d g e o n t h e l o n g -t er m 
eff ect s of t h e cl os e d-l o o p f e at ur e o n o v ersti m ul ati o n.      
5.  O bj e cti v e s  
5. 1  Pri m ar y O bj e cti v e s  
T o d e m o nstr at e t h at t h e pr o p orti o n of l o w -b ack a n d / or l e g p ai n s u bj ects h avi n g a r e d ucti o n i n 
o v ersti m ul ati o n s e ns ati o n wit h N e ur o S e ns e O n c o m p ar e d t o N e ur o S e ns e Off, at t h e r a n d o miz ati o n a n d 
i n-cli nic t esti n g visit, exc e e ds a p erf or m a nc e g o al of 5 0 %.  
O v ersti m ul ati o n is d efi n e d as a n u nc o mf ort a bl e s e ns ati o n of sti m ul ati o n (i nt e ns e ti n gli n g, s h oc ki n g, 
j olti n g) br o u g ht a b o ut by pr ot oc ol-pr escri b e d activiti es 
. T his 
o v ersti m ul ati o n s e ns ati o n is tr a nsi e nt a n d r ev ers e d by t h e s u bj ect r et ur ni n g t o a n e utr al p ositi o n.  
5. 2  S e c o n d ar y O bj e cti v e s  
1.  T o c h ar act eriz e t h e effic ac y of s pi n al c or d sti m ul ati o n (S C S) t h er a py f or t h e tr e at m e nt of ov er all p ai n 
(f or l o w-b ack a n d / or l e g p ai n s u bj ects) by ev al u ati n g t h e effic acy r es p o n d er r at e. T h e effic ac y 
r es p o n d er r at e is d efi n e d as t h e p erc e nt a g e of i m pl a nt e d s u bj ects w h o ex p eri e nc e at l e ast a 5 0 % 
i m pr ov e m e nt i n o v er all p ai n, as m e as ur e d by t h e Vis u al A n al o g u e Sc al e ( V A S), fr o m B as eli n e t o t h e 
3- M o nt h Visit.  
2.  T o c h ar act eriz e t h e effic ac y r es p o n d er r at e wit hi n i n e ac h t y p e of p ai n (l o w-b ac k or l e g)  f or lo w -b ac k 
a n d / or l e g p ai n s u bj ects, as m e as ur e d by t h e p ai n -s p ecific V A S, fr o m B as eli n e t o t h e 3-M o nt h Visit.  
T h e l o w -b ac k r es p o n d er r at e will b e c h ar act eriz e d f or s u bj ects wit h b as eli n e b ac k V A S ≥ 6 0 m m , a n d 
t h e l e g r es p o n d er r at e will b e c h ar act eriz e d f or s u bj ects wit h b as eli n e l e g V A S ≥ 6 0 m m.      
 
 
 
  
 
 
  
  
 
 
 
 
 
  
  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 5  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
6.  St u d y D e si g n  
T h e st u dy is ex p ect e d t o b e c o n d uct e d at u p t o t e n st u dy sit es l oc at e d i n A ustr ali a.  U p t o 1 4 0 s u bj ects 
will b e e nr oll e d i n t h e st u dy t o e ns ur e  u p t o 5 7 s u bj ects wit h l o w-b ac k  a n d / or l e g p ai n a n d u p t o 1 2 
s u bj ects wit h u p p er li m b a n d/ or n ec k  p ai n  ar e i m pl a nt e d wit h t h e st u dy d e vic e .   
U p t o 1 1 0 I nc e pti v d evic es m a y  b e us e d i n t h e st u dy.   T o r e d uc e t h e p ossi bilit y of at y pic al r es ults fr o m a 
sit e o v erl y i nfl u e nci n g t h e st u dy, n o m or e t h a n 2 0 % of t h e t ot al i m pl a nt e d p o p ul ati o n will b e fr o m e ac h 
sit e u nl ess t h e sit e g ets pr e-a p pr o v al fr o m M e dtr o nic f or a d diti o n al i m pl a nts. 
S u bj ects will b e e nr oll e d,  a n d b as eli n e d at a will b e c oll ect e d.  T h os e m e eti n g all i ncl usi o n crit eri a a n d n o 
excl usi o n crit eri a will  u n d er g o a d evic e tri al.  S u bj ects wit h s uffici e nt p ai n r eli ef d uri n g t h e tri al will b e 
i m pl a nt e d wit h t h e st u dy d e vic e a n d u n d er g o D e vic e O pti miz ati o n f or 1- Mo nt h .  A p pr oxi m at ely  1-
M o nt h p ost  D e vic e Acti v ati o n, s u bj ects will u n d er g o i n -cli nic t esti n g.  S u bj ects will b e r a n d o miz e d at t h e 
i n-cli nic visit t o o n e of t h e t w o s e q u e nc es: N e ur o S e ns e O n f oll o w e d by N e ur o S e ns e Off or N e ur o S e ns e 
Off f oll o w e d by N e ur o S e ns e O n.  S u bj ects will b e bli n d e d t o t h e s etti n gs t est e d.  I n e ac h s etti n g, 
s u bj ects will p erf or m a s eri es of activiti es a n d ask e d t o r at e t h e i nt e nsit y of t h e ov ersti m ul ati o n 
s e ns ati o n t h ey ex p eri e nc e d w hil e p erf or mi n g t h e activit y usi n g a 5-p oi nt Li k ert sc al e.  
 
It is r ec o m m e n d e d t h at t h e 
N e ur o S e ns e f e at ur e b e t ur n e d O N at t h e e n d of t h e i n -cli nic t esti n g visit, u nl ess t h e p ati e nt pr ef ers t h e 
N e ur o S e ns e O F F s etti n g.  All su bj ects will t h e n b e  f oll o w e d f or u p t o 2 4-m o nt hs  f oll o wi n g d e vic e 
activ ati o n ; sc h e d ul e d st u dy visits will occ ur at 3-, 6-, 1 2-, 1 8-, a n d 2 4 -m o nt hs p ost d e vic e acti v ati o n .  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 6  of 1 1 7  
 
 
 
 
 
6. 1  D ur ati o n  
T h e ex p ect e d t ot al st u dy d ur ati o n is a p pr oxi m at el y 4 8  m o nt hs , r e pr es e nti n g a p pr oxi m at ely 2 4  m o nt hs 
of e nr oll m e nt a n d 2 4 m o nt hs of s u bj ect f oll o w-u p . S u bj ects will exit t h e st u dy aft er c o m pl eti o n of t h eir 
2 4  Mo nt h V isit.   
6. 2  R ati o n al e 
S pi n al C or d Sti m ul ati o n is a w ell -est a blis h e d t h er a py f or t h e tr e at m e nt of c hr o nic p ai n wit h n u m er o us 
cli nic al st u di es d e m o nstr ati n g eff ectiv e p ai n r eli ef. 2 4 – 2 7, 1 8, 2 8  R ec e ntly, eff ectiv e p ai n r eli ef usi n g 
c o nv e nti o n al, l o w-d os e t h er a py c o u pl e d wit h a cl os e d -l o o p al g orit h m b as e d o n p hysi ol o gic al f e e d b ac k 
fr o m t h e i m pl a nt e d s ubj ect h as b e e n d e m o nstr at e d. 2 9  T h e us e of a cl os e d -l oo p al g orit h m i n S C S is n ot a 
n e w c o nc e pt.  M e dtr o nic first i ntr o d uc e d a n e arl y f or m of a cl os e d -l o o p al g orit h m b as e d o n p ositi o n al 
c h a n g es i n 2 0 1 1, 2 8 w hic h d e m o nstr at e d b e n efit t o p ati e nts wit h si g nific a nt p ai n r eli ef a n d c o nv e ni e nc e.  
P ati e nts tr e at e d wit h S C S syst e ms r e p ort u n d er -sti m ul ati o n or o v er-sti m ul ati o n i n d uc e d by m ov e m e nt. 3 0  
T h e v ari ati o n i n p erc ei v e d i nt e nsit y is oft e n attri b ut e d t o c h a n g es i n t h e dist a nc e b et w e e n t h e i m pl a nt e d 
l e a d a n d t h e s pi n al c or d r es ulti n g i n i ncr e as e d or d ecr e as e d n u m b ers of d ors al c ol u m n n er v e fi b ers 
r ecr uit e d d uri n g sti m ul ati o n.  P u blis h e d pr e-cli nic al a n d cli nic al f e asi bility d at a h av e d e m o nstr at e d t h e 
f e asi bilit y t o m e as ur e E C A Ps i n t h e s pi n al c or d fr o m t h e e pi d ur al s p ac e.1 4, 1 3, 1 5 T h es e st u di es s u p p ort t h e 
us e of f e at ur es extr act e d fr o m t h e E C A P as a m e as ur e of t h e l ev el of n e ur al r ecr uit m e nt t o s er v e as a 
f e e d b ac k si g n al f or c o nti n u o us a dj ust m e nt of sti m ul ati o n a m plit u d e (i. e., cl os e d-l o o p c o ntr ol).     
T h e pri m ar y o bj ecti v e f or t his st u dy is t o d e m o nstr at e t h at t h e pr o p orti o n of s u bj ects h avi n g  a r e d ucti o n 
i n o v ersti m ul ati o n s e ns ati o n wit h N e ur o S e ns e O n c o m p ar e d t o N e ur o S e ns e Off exc e e ds a p erf or m a nc e 
g o al of 5 0 % w hic h hi g hli g hts t h e n e w d evic e f e at ur e.  
A d diti o n all y, s ec o n d ar y o bj ecti v es t o c h ar act eriz e i m pr o v e m e nt i n p ai n h as hist oric all y b e e n us e d i n S C S 
st u di es. 
 
7.  Pr o d u ct D e s cri pti o n  
7. 1  G e n er al  
T h e I nc e ptiv Syst e m c o nsists of i nv esti g ati o n al a n d m ar k et -r el e as e d pr o d ucts. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 7  of 1 1 7  
 
 
 
 
 
  
 
Fi g ur e 4 : S y st e m O v er vi e w 
T h e st u dy will b e c o n d uct e d usi n g t h e pr o d ucts d escri b e d i n T a bl e 3 .  I nstr ucti o ns f or us e of t h e pr o d ucts  
us e d i n t his st u dy ar e pr ovi d e d i n t h eir r es p ecti v e m a n u als or I nv esti g at or’s Br oc h ur e. 
T a bl e 3 : S y st e m P r o d u ct I nf or m ati o n  
Pr o d uct  
M o d el  
M a n uf act ur er  
I n v esti g ati o n al or M ar k et-
r el e as e d 
I nc e ptiv I m pl a nt a bl e 
N e ur osti m ul at or  
9 7 7 1 1 9  
M e dtr o nic  
I nv esti g ati o n al 
Wir el ess Ext er n al 
N e ur osti m ul at or  
9 7 7 2 5  
Pl ex us  
M ar k et -r el e as e d 
L e a ds:  
V ectris ™ S ur e Sc a n ™ M RI 1x 8 
C o m p act  
Or  
S p ecif y ™ S ur e Sc a n ™ M RI 5 - 6- 5 
9 7 7 A 2 6 0 , 
9 7 7 A 2 7 5, 
9 7 7 A 2 9 0  
 
9 7 7 C 1 6 5 , 
9 7 7 C 1 9 0  
M e dtr o nic  
I nv esti g ati o n al u p o n 
o p e ni n g  
L e a d: 
V ectris ™ 1x 8 C o m p act  
9 7 7 D 2 6 0 , 
9 7 7 D 2 7 5, 
9 7 7 D 2 9 0  
M e dtr o nic  
M ar k et -r el e as e d 
Cli nici a n T a bl et  
C T 9 0 0 D  
a n d/ or 
C T 9 0 0 E  
S a ms u n g  
I nv esti g ati o n al 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 8  of 1 1 7  
 
 
 
 
 
Pr o d uct  
M o d el  
M a n uf act ur er  
I n v esti g ati o n al or M ar k et-
r el e as e d 
Cli nici a n Pr o gr a m m er 
A p plic ati o n ( v ersi o n 1. 0 . 2 5 7 6 
or n e w er ) 
A 7 1 4 0 0  
M e dtr o nic  
I nv esti g ati o n al 
Sti m ul ati o n Tri ali n g Cli nici a n 
Pr o gr a m m er A p plic ati o n 
( v ersi o n 2. 0. 2 4 7 or n e w er ) 
A 7 1 3 0 0  
M e dtr o nic  
I nv esti g ati o n al 
Pr o gr a m m er Pl atf or m 
S oft w ar e -C o m m u nic ati o n 
M a n a g er A p plic ati o n (v ersi o n 
1. 0. 1 2 1 3  or n e w er ) 
A 9 0 1  
M e dtr o nic  
I nv esti g ati o n al 
P ati e nt D at a S ervic e 
A p plic ati o n ( v ersi o n 1. 0. 8 2 8  or 
n e w er ) 
A 9 0 2  
M e dtr o nic  
I nv esti g ati o n al 
P ati e nt H a n ds et  
H H 9 0  
S a ms u n g  
I nv esti g ati o n al 
P ati e nt Pr o gr a m m er 
A p plic ati o n (v ersi o n 1. 0 . 8 6 4 or 
n e w er ) 
A 7 2 4 0 0  
M e dtr o nic  
I nv esti g ati o n al 
P ati e nt Pr o gr a m m er Tri ali n g 
A p plic ati o n (v ersi o n 5. 0 . 8 0 0 or 
n e w er ) 
A 7 2 3 0 0  
M e dtr o nic  
I nv esti g ati o n al 
P ati e nt T el e m etry 
C o m m u nic at or  
T M 9 1 S C S 2  
J a bil 
I nv esti g ati o n al 
R ec h ar g er A p plic ati o n (v ersi o n 
1. 0. 5 9 6  or n e w er ) 
A 9 0 3 0 0  
M e dtr o nic  
I nv esti g ati o n al 
R ec h ar g er  
W R 9 2 3 0  
J a bil 
I nv esti g ati o n al 
R ec h ar g er S u bsyst e m S C S 
T h er a py  
R S 7 2 3 0  
J a bil 
M ar k et -r el e as e d 
C o m m u nic at or  
8 8 8 0 T 2  
Pl exis  
M ar k et -r el e as e d 
C o n n ect or Pl u g  
B 3 1 0 6 0  
M e dtr o nic  
M ar k et -r el e as e d 
B o ot  
3 7 5 0 0 3 0 1, 
3 7 5 0 0 3 0 2  
J a bil 
M ar k et -r el e as e d 
R ec h ar g er B elt  
F P 9 0 0 0  ( S, M, 
L, XL) 
J a bil 
M ar k et -r el e as e d 
C arr yi n g C as e  
N ot 
a p plic a bl e  
Pr ot ec h  
M ar k et -r el e as e d 
All m at eri als t h at m a y c o nt act tiss u es a n d/ or b o dy fl ui ds ar e pr es e nt e d i n  T a bl e 4 . 
T a bl e 4 : M at eri al s i n c o nt a ct wit h ti s s u e s a n d / or b o d y fl ui d s 
Pr o d uct  
M o d el  
M at eri als  
I m pl a nt a bl e N e ur osti m ul at or 
I nc e ptiv I m pl a nt a bl e N e ur osti m ul at or 9 7 7 1 1 9 
•  
Tit a ni u m gr a d e 9 Ti -3 A 1 -2. 5 V  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 2 9  of 1 1 7  
 
 
 
 
 
Pr o d uct  
M o d el  
M at eri als  
•  
Tit a ni u m Gr a d e 5 Ti -6 Al -4 V  
•  
Tit a ni u m Gr a d e 1  
•  
P olys ulf o n e wit h 0. 5 % tit a ni u m di oxi d e; 
sil ox a n e c o at e d, 
•  
Li q ui d silic o n e r u b b er ( Sil astic ® Q 7-4 8 5 0) wit h 
tit a ni u m di oxi d e  
•  
E n h a nc e d -t e ar r esist a nt ( E T R) silic o n e r u b b er 
( Sil astic ® Q 7-4 7 3 5)  
•  
Silic o n e a d h esiv e, ( N usil M E D -2 0 0 0)  
L e a ds: 
V ectris ™ S ur e Sc a n ™ M RI 1x 8 
C o m p act  
 
 
 
 
 
 
 
 
S p ecif y ™ S ur e Sc a n ™ M RI 5 - 6- 5 
9 7 7 A 2 6 0, 
9 7 7 A 2 7 5, 
9 7 7 A 2 9 0  
 
 
 
 
 
 
9 7 7 C 1 6 5 , 
9 7 7 C 1 9 0  
•  
E p oxy, fl u or o p ol y m er, M P 2 5 N, pl ati n u m -
iri di u m, p oly ur et h a n e, t a nt al u m 
•  
A nc h or: Silic o n e r u b b er  
•  
A nc h or dis p e ns er t o ol: P olyc ar b o n at e, 
p ol yt etr afl u or o o et hy e n e, St ai nl ess st e el 
•  
G ui d e wir e, n e e dl es, t u n n eli n g r o d, t u n n eli n g 
ti p, t u b e: S t ai nl ess st e el 
•  
St yl ets: P ol pr o pyl e n e, S t ai nl ess st e el 
 
 
•  
Pl ati n u m -iri di u m, Silic o n e r u b b er, 
P oly ur et h a n e, Tit a ni u m  di o xi d e, M P 3 5 N, E p oxy 
•  
A nc h or: Silic o n e r u b b er  
•  
P assi n g el e v at or: Ac et al r esi n, Silic o n e r u b b er, 
B ari u m s ulf at e,  
•  
L e a d bl a n k: Silic o n e r u b b er, B ari u m s ulf at e 
•  
T u n n eli n g t o ols: St ai nl ess st e el, Fl u or o p ol y m er  
•  
T or q u e wr e nc h:  P oly m er , St ai nl ess st e el 
Ext er n al N e ur osti m ul at or  
Wir el ess Ext er n al N e ur osti m ul at or  
9 7 7 2 5  
•  
A B S/ p olyc ar b o n at e bl e n d Cyc ol oy  
•  
Cl e ar p oly est er fil m  
L e a d: 
V ectris ™ 1x 8 C o m p act  
9 7 7 D 2 6 0, 
9 7 7 D 2 7 5, 
9 7 7 D 2 9 0  
•  
E p oxy, fl u or o p ol y m er, M P 3 5 N, pl ati n u m -
iri di u m, p oly ur et h a n e, t a nt al u m 
•  
G ui d e wir e, n e e dl es: st ai nl ess st e el  
•  
St yl et: P ol pr o pyl e n e, st ai nl ess st e el  
Cli nici a n Pr o gr a m m er  
Cli nici a n  T a bl et  
C T 9 0 0 D 
a n d/ or 
C T 9 0 0 E  
N o n -i m pl a nt a bl e 
Cli nici a n Pr o gr a m m er A p plic ati o n  
A 7 1 4 0 0  
N o n -i m pl a nt a bl e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 0  of 1 1 7  
 
 
 
 
 
Pr o d uct  
M o d el  
M at eri als  
Sti m ul ati o n Tri ali n g Cli nici a n 
Pr o gr a m m er A p plic ati o n  
A 7 1 3 0 0  
N o n -i m pl a nt a bl e 
Pr o gr a m m er Pl atf or m  S oft w ar e -
C o m m u nic ati o n M a n a g er A p plic ati o n  
A 9 0 1  
N o n -i m pl a nt a bl e 
P ati e nt D at a S ervic e A p plic ati o n  
A 9 0 2  
N o n -i m pl a nt a bl e 
R ec h ar g er A p plic ati o n  
A 9 0 3 0 0  
N o n -i m pl a nt a bl e 
P ati e nt Pr o gr a m m er  
P ati e nt H a n ds et  
H H 9 0  
N o n -i m pl a nt a bl e 
P ati e nt Pr o gr a m m er A p plic ati o n  
A 7 2 4 0 0  
N o n -i m pl a nt a bl e 
P ati e nt Pr o gr a m m er Tri ali n g 
A p plic ati o n  
A 7 2 3 0 0  
N o n -i m pl a nt a bl e 
R ec h ar g er A p plic ati o n  
A 9 0 3 0 0  
N o n -i m pl a nt a bl e 
Ot h er  
 
 
P ati e nt T el e m etry C o m m u nic at or  
T M 9 1 -S C S 2  
N o n -i m pl a nt a bl e 
R ec h ar g er  
W R 9 2 3 0  
N o n -i m pl a nt a bl e 
R ec h ar g er S u bsyst e m S C S T h er a py  
R S 7 2 3 0  
N o n -i m pl a nt a bl e 
C o m m u nic at or  
8 8 8 0 T 2  
N o n -i m pl a nt a bl e 
C o n n ect or Pl u g  
B 3 1 0 6 0  
5 5 D P oly ur et h a n e  
B o ot  
3 7 5 0 0 3 0 1, 
3 7 5 0 0 3  
N o n -i m pl a nt a bl e 
R ec h ar g er B elt  
F P 9 0 0 0  
N o n -i m pl a nt a bl e 
C arr yi n g C as e  
N ot 
a p plic a bl e  
N o n -i m pl a nt a bl e 
 
7. 1. 1  I n c e pti v  I m pl a nt a bl e N e ur o sti m ul at or  
T h e I nc e ptiv i m pl a nt a bl e n e ur osti m ul at or is a r ec h ar g e a bl e, m ulti pr o gr a m m a bl e de vic e t h at d eli v ers 
el ectric al sti m ul ati o n t hr o u g h o n e or  m or e l e a ds.  T h e sti m ul ati o n s etti n g s ar e st or e d i n pr o gr a ms t o 
t ar g et s p ecific eff ects or ar e as. A pr o gr a m is a s p ecific c o m bi n ati o n of p uls e wi dt h, r at e, a n d i nt e nsity 
s etti n gs acti n g o n a s p ecific el ectr o d e c o m bi n ati o n.   
M e dtr o nic h as d e v el o p e d a n o pti o n al cl os e d -l o o p f e at ur e t o i m pr ov e a p ati e nt’s ex p eri e nc e wit h S C S 
t h er a py, s p ecific ally t ar g eti n g o v ersti m ul ati o n.  T h e cl os e d-l o o p al g orit h m is a bl e t o s e ns e t h e b o dy's 
p hysi ol o gic al E C A P r es p o ns e, a n d a ut o m atic ally r e act, b as e d o n t h e s pi n al c or d's r es p o ns e t o 
sti m ul ati o n. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 1  of 1 1 7  
 
 
 
 
 
7. 1. 2  V e ctri s S ur e S c a n M R I 1 x 8 C o m p a ct  
T h e  p erc ut a n e o us  l e a ds ar e c o n n ect e d t o t h e i m pl a nt a bl e n e ur osti m ul at or.  E ac h l e a d h as el ectr o d es o n 
t h e dist al e n d; t h e pr oxi m al (c o n n ect or) e n d fits i nt o a n 8-c o n d uct or c o n n ect or.  A st yl et c a n b e i ns ert e d 
i nt o t h e pr oxi m al e n d of t h e l e a d t o ai d i n p ositi o ni n g t h e l e a d. 
7. 1. 3  S p e cif y S ur e S c a n M R I 5 - 6- 5 
T h e s ur gic al l e a ds ar e c o n n ect e d t o t h e i m pl a nt a bl e n e ur osti m ul at or.  T h e l e a d h as 1 6 el ectr o d es o n t h e 
dist al e n d; t w o pr oxi m al e n ds fit i nt o 8- c o d uct or c o n n ect ors.  U p t o t hr e e  l o w-b ac k a n d / or l e g s u bj ects 
m a y b e i m pl a nt e d wit h s ur gic al l e a ds.  
7. 1. 4  Wir el e s s E xt er n al N e ur o sti m ul at or  
T h e Wir el ess Ext er n al N e ur osti m ul at or is p art of a n e ur osti m ul ati o ns syst e m us e d f or i ntr a o p er ati v e 
t esti n g d uri n g l e a d pl ac e m e nt a n d f or tri al sti m ul ati o n o utsi d e of t h e o p er ati n g r o o m.  
7. 1. 5  V e ctri s M R I 1 x 8 C o m p a ct  
T h e  tri al l e a ds ar e c o n n ect e d t o t h e wir el ess ext er n al  n e ur osti m u l at or.  E ac h l e a d h as el ectr o d es o n t h e 
dist al e n d; t h e pr oxi m al (c o n n ect or) e n d fits i nt o a n 8 -c o n d uct or c o n n ect or.  A styl et c a n b e i ns ert e d i nt o 
t h e pr oxi m al e n d of t h e l e a d t o ai d i n p ositi o ni n g t h e l e a d.  T h e tri al l e a ds ar e c o ntr ai n dic at e d f or l o n g -
ter m i m pl a nt ati o n a n d m ust b e r e m ov e d wit hi n t e n d ays of i m pl a nt.  
7. 1. 6  B o ot  
T h e b o ot is a n ext er n al si n gl e -us e -o nly acc ess or y t h at is us e d wit h t h e wir el ess ext er n al n e ur osti m ul at or 
t o a d h er e t h e wir el ess ext er n al n e ur osti m ul at or ext er n all y t o t h e p ati e nt’s b o d y d uri n g t h e d ur ati o n of 
t h e tri al p eri o d. 
7. 1. 7  Cli ni ci a n T a bl et  
T h e Cli nici a n T a bl et , a S a ms u n g t a bl et wit h A n dr oi d o p er ati n g s yst e m, is a n o nst eril e, c o m m erci ally 
av ail a bl e, off -t h e s h elf, n o n -m e dic al d e vic e.  T h e Cli nici a n Pr o gr a m m er A p plic ati o n a n d t h e Sti m ul ati o n 
Cli nici a n Tri ali n g Pr o gr a m m er A p plic ati o n o p er at e o n t his pl atf or m.  
7. 1. 8  Cli ni ci a n Pr o gr a m m er A p pli c ati o n  
T h e Cli nici a n Pr o gr a m m er A p plic ati o n ( C P A) is a m o bil e m e dic al a p plic ati o n d esi g n e d f or us e by 
cli nici a ns t o i nt err o g at e a n d pr o gr a m m e dic al d evic es. It is d esi g n e d t o c o nfi g ur e a n d m a n a g e S C S 
t h er a py p ar a m et ers by t h e cli nici a ns f or I nc e ptiv.  T h e C P A will r u n o n t h e Cli nici a n T a bl et w hic h is a 
n o n -m e dic al off -t h e-s h elf t a bl et.  A d diti o n ally , wit h t h e C P A, t h e C o m m u nic ati o n M a n a g er A p plic ati o n  
( n o n-m e dic al), a n d P ati e nt D at a S er vic es  A p plic ati o n  ( n o n-m e dic al) will b e utiliz e d. T h e C o m m u nic at or 
will s erv e as a t el e m etr y bri d g e b et w e e n t h e Cli nici a n T a bl et a n d I nc e pti v. 
7. 1. 9  P ati e nt Pr o gr a m mi n g A p pli c ati o n  
T h e P ati e nt Pr o gr a m mi n g A p plic ati o n ( P P A) will o p er at e o n t h e P ati e nt H a n ds et a n d b e us e d by p ati e nts 
( a n d/ or t h eir c ar e gi v ers) t o m a n a g e t h eir t h er a py pr ovi d e d by I nc e ptiv. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 2  of 1 1 7  
 
 
 
 
 
7. 1. 1 0  
Sti m ul ati o n Tri ali n g Cli ni ci a n Pr o gr a m m er A p pli c ati o n  
T h e Sti m ul ati o n Tri ali n g Cli nici a n Pr o gr a m m er A p plic ati o n all o ws cli nici a ns t o pr o gr a m wir el ess ext er n al 
n e ur osti m ul at ors d uri n g tri ali n g by a dj usti n g t h e r at e, p uls e wi dt h a n d a m plit u d e of t h e t h er a py 
pr o vi d e d t o t h e p ati e nt.  
7. 1. 1 1  
P ati e nt Pr o gr a m m er Tri ali n g A p pli c ati o n  
T h e P ati e nt Pr o gr a m m er Tri al A p plic ati o n o p er at es o n t h e P ati e nt H a n ds et a n d will b e us e d by p ati e nts 
t o m a n a g e t h eir t h er a py d uri n g a tri al. T h e P ati e nt Pr o gr a m m er Tri al A p plic ati o n all o ws t h e p ati e nt t o 
m a k e t h er a py pr o gr a m mi n g a dj ust m e nts t o  t h e wir el ess ext er n al n e ur osti m ul at or .  T h e P ati e nt H a n ds et 
h as a us er i nt erf ac e dis pl a y a n d Bl u et o ot h i nt erf ac e t o t h e wir el ess ext er n al n e ur osti m ul at or . T h e 
P ati e nt H a n ds et is c o nstr ai n e d t o a C o m m erci al -Off -T h e -S h elf A n dr oi d m o bil e p h o n e . 
7. 1. 1 2  
P ati e nt T el e m etr y C o m m u ni c at or  
T h e P ati e nt H a n ds et w or ks i n c o nj u ncti o n wit h t h e P ati e nt T el e m etry C o m m u nic at or t o pr ovi d e t h e 
pr o gr a m mi n g/c o ntr olli n g c a p a biliti es t o p ati e nts. S p ecific all y, a c o m m u nic ati o n bri d g e is f or m e d fr o m 
t h e P ati e nt H a n ds et, usi n g Bl u et o ot h L o w E n er gy ( BL E) si g n als, t hr o u g h t h e T el e m etry M o d ul e t o 
I nc e ptiv, usi n g T el-M a n d T el -N p c o m m u nic ati o n pr ot oc ols, r es p ectiv ely.  
7. 1. 1 3  
C o m m u ni c at or  
T h e C o m m u nic at or is c o nsi d er e d p art of t h e cli nici a n pr o gr a m m er s yst e m. T h e C o m m u nic at or w as 
ori gi n all y d ev el o p e d f or us e acr oss M e dtr o nic N e ur o m o d ul ati o n t h er a pi es. It is a n o n -st eril e, b att ery-
o p er at e d, ext er n al d e vic e d esi g n e d t o cr e at e a c o m m u nic ati o n bri d g e b et w e e n t h e M o bil e Pl atf or m a n d 
I nc e ptiv. 
7. 1. 1 4  
C o n n e ct or Pl u g 
T h e C o n n ect or Pl u g is a st eril e d e vic e t h at is i nt e n d e d t o b e i ns ert e d i nt o t h e u n us e d c o n n ect or of 
I nc e ptiv. 
7. 1. 1 5  
R e c h ar g er S u b s y st e m  
T h e R ec h ar g er S u bs yst e m is a kit t h at is d esi g n e d t o s u p p ort t h e p ati e nt i n t h eir r ec h ar g e n e e ds.  
T h e fix ati o n b elt is i nt e n d e d t o s u p p ort t h e R ec h ar g er d uri n g a p ati e nt’s r ec h ar g e s essi o n; h o w ev er, t h e 
p ati e nt m a y c h o os e t o h ol d t h e r ec h ar g er m a n u all y or vi a ot h er m e a ns. T h e R ec h ar g er B elt is n ot 
r e q uir e d f or t h e r ec h ar g er t o ac hi e v e its i nt e n d e d p ur p os e, w hic h is t o r ec h ar g e  t h e I nc e ptiv.  
•  
R ec h ar g er  a n d a p plic ati o n  
•  
F ix ati on B elt  
•  
C D 9 0 0 0 C h ar gi n g D ock + P o w er A d a pt er  
•  
U S B c or d a n d A C a d a pt or (c o m m erci al , off -t h e-s h elf n o n -m e dic al d evic es)  
•  
Syst e m c arr yi n g c as e ( n o n -m e dic al d e vic e)  
7. 2  M a n uf a ct ur er  
T h er e ar e s e v er al ma n uf act ur e rs of t h e st u dy pr o d ucts, s e e T a bl e 3 . 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 3  of 1 1 7  
 
 
 
 
 
7. 3  P a c k a gi n g 
T h e I nc e ptiv d evic e a n d acc o m p a nyi n g i nv esti g ati o n al  pr o d uct s will b e  l a b el e d “ Excl usi v ely f or cli nic al 
i nv esti g ati o ns”. 
7. 4  I nt e n d e d P o p ul ati o n  
T h e st u dy d evic e is i n dic at e d f or S C S as a n ai d i n t h e m a n a g e m e nt of p ati e nts wit h c hr o nic, i ntr act a bl e 
p ai n of t h e tr u n k a n d/ or li m bs.   St u dy eli gi bilit y crit eri a m ust b e m et t o p arti ci p at e, s e e S ecti o n  9 .  
7. 5  E q ui p m e nt  
T h e f oll o wi n g e q ui p m e nt m ust b e a v ail a bl e at e ac h st u dy sit e t o s u p p ort st u dy acti viti es:  
•  
Fl u or osc o py/x -r ay wit h el ectr o nic o ut p ut  
T his  e q ui p m e nt will b e m ai nt ai n e d/c ali br at e d acc or di n g t o t h e st u dy sit e ’s st a n d ar d pr ot oc ol.  
M ai nt e n a nc e a n d c ali br ati o n r e p orts m a y  b e m o nit or e d p eri o dic ally by t h e m o nit or.  
7. 6  Pr o d u ct U s e  
I nstr ucti o ns f or I nc e pti v a n d acc o m p a nyi n g pr o d ucts will b e pr o vi d e d i n t h e I nv esti g at or’s Br oc h ur e.   
R ef er t o existi n g m a n u als f or m ar k et r el e as e d pr o d uct.  
7. 7  Pr o d u ct Tr ai ni n g M at eri al s  
I nv esti g at ors will b e c h os e n t o p artici p at e i n t his st u dy b as e d o n b ei n g q u alifi e d by tr ai ni n g, e d uc ati o n, 
a n d r el e v a nt ex p eri e nc e a p pr o pri at e f or t h e us e of s pi n al c or d si m ul at ors.  St u dy s p ecific tr ai ni n g will b e 
c o n d uct e d p erti n e nt t o t h e i nv olv e m e nt of p ers o n n el c o n d ucti n g st u dy activiti es  a n d I nv esti g at or 
r es p o nsi biliti es.  All I nv esti g at ors a n d sit e p ers o n n el will b e tr ai n e d o n t h e Cli nic al I nv esti g ati o n Pl a n 
( CI P) pri or t o t h eir p artici p ati o n o n t h e st u dy.    
7. 8  Pr o d u ct R e c ei pt a n d Tr a c ki n g  
Sit es wit h t h es e cli nic ally l a b el e d pr o d uct s will tr ac k dis p ositi o n u p o n r ec ei pt or r et ur n of t h e pr o d ucts, 
as w ell as u p o n i m pl a nt or ex pl a nt of t h e pr o d uct.  Tr ac ki n g i ncl u d es d at es a n d q u a ntiti es  r ec eiv ed, us e d, 
ex pl a nt e d a n d r et ur n e d.  L ot/s eri al n u m b ers a n d ex pir ati o n d at es will b e d oc u m e nt e d  an d us e d f or 
tr ac e a bility.  All of t h es e el e m e nts will b e e nt er e d o n a n el ectr o nic C as e R e p ort F or m ( e C R F ).  
7. 9  Pr o d u ct St or a g e  
I nv esti g ati o n al pr o d uct, o nc e r ec eiv e d at t h e st u dy sit e, m ust b e st or e d i n a s ec ur e l oc ati o n at t h e st u dy 
sit e. It is t h e r es p o nsi bilit y of t h e i nv esti g at or t o c orr ectl y h a n dl e, st or e, a n d tr ack t h e i nv esti g ati o n al 
pr o d ucts m ai nt ai n e d at t h e st u dy sit e.  I nv esti g ati o n al pr o d ucts will b e us e d o nly i n t h e cli nic al st u dy 
acc or di n g t o t h e CI P.  
7. 1 0  Pr o d u ct R et ur n  
All ex pl a nt e d d e vic es ( d e vic e s or p er m a n e nt l e a ds) s h o ul d b e r et ur n e d t o M e dtr o nic f or a n al ysis w h e n 
p er missi bl e by l oc al l a ws a n d r e g ul ati o ns. If t h e pr o d ucts ar e ex pl a nt e d b ut n ot r et ur n e d, a j ustific ati o n 
will b e r e p ort e d o n t h e a p pr o pri at e c as e r e p ort f or ms or dis p ositi o n l o gs. T o  r ec eiv e a R et ur n e d Pr o d uct 
M ail er Kit, pl e as e c o nt act y o ur l oc al M e dtr o nic fi el d p ers o n n el.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 4  of 1 1 7  
 
 
 
 
 
7. 1 1  Pr o d u ct A c c o u nt a bilit y  
Pr o d uct d eli v er y  
M ar k et -r el e as e d pr o d ucts: 
C o m m erci all y a v ail a bl e pr o d uct s u p pl y will b e m a n a g e d i n a m a n n er c o nsist e nt wit h ot h er m ar k et -
r el e as e d pr o d ucts. 
I nv esti g ati o n al pr o d ucts: 
Inv esti g ati o n al pr o d uct s will b e distri b ut e d t o a st u dy sit e o nl y w h e n M e dtr o nic h as r ec ei v e d all r e q uir e d 
d oc u m e nt ati o n a n d h as n otifi e d t h e st u dy sit e of st u dy sit e activ ati o n. Distri b uti o n of i nv esti g a ti o n al 
pr o d uct t o st u dy sit es d uri n g t h e st u dy will b e m a n a g e d by M e dtr o nic a n d c a n o nl y b e or d er e d by 
M e dtr o nic p ers o n n el.  
Pr o d uct r ec ei pt a n d tr ac ki n g  
M ar k et -r el e as e d pr o d ucts: 
T h er e ar e n o a d diti o n al l oc al r e q uir e m e nts r el at e d t o t h e m ar k et -r el e as e d pr o d uct b ey o n d w h at is 
c oll ect e d by M e dtr o nic o n t h e e C R F, t his is t h e I nv esti g at or’s r es p o nsi bilit y a n d s h o ul d b e r ec or d e d i n 
t h e s u bj ect’s m e dic al r ec or ds, b ut will n ot b e c oll ect e d by M e dtr o nic. 
I nv esti g ati o n al pr o d ucts: 
T h e st u dy sit e is r es p o nsi bl e f or m ai nt ai ni n g tr ac ki n g of t h e i nv esti g ati o n al pr o d ucts d uri n g t h e st u dy. 
T h e tr acki n g m et h o d mi g ht v ary, b ut c o ul d us e eit h er el ectr o nic or p a p er acc o u nt a bilit y l o gs pr o vi d e d by 
M e dtr o nic.   T h e a cc o u nt a bilit y l o gs m ust b e m ai nt ai n e d at e ac h st u dy sit e a n d u p d at e d w h e n t h e 
i nv esti g ati o n al pr o d uct is r ec eiv e d, o p e n e d, i m pl a nt e d, ex pl a nt e d, dis p os e d of or r et ur n e d t o M e dtr o nic. 
I n a d diti o n t o tr ac ki n g t h e d at e of ev e nts, t h e acc o u nt a bilit y l o g tr acks pr o d uct i nf or m ati o n i ncl u di n g, 
b ut n ot li mit e d t o, d at e, m o d el/s eri al n u m b er, a n d ex pir ati o n d at e f or t h e r ec ei v e d pr o d uct, s u bj ect I D 
of t h e i m pl a nt e d s u bj ect, r e as o n(s) f or a n d m et h o d of d estr ucti o n/ dis p os al f or ex pl a nt e d c o m p o n e nts 
n ot r et ur n e d t o M e dt r o nic (if a p plic a bl e), a n d n a m e of t h e p ers o n r es p o nsi bl e f or r et ur n or 
d estr ucti o n/ dis p os al (if a p plic a bl e).  
M e dtr o nic will p erf or m p eri o dic r ec o ncili ati o n of t h e i nv esti g ati o n al pr o d uct t o e ns ur e tr ac e a bilit y.  
8.  St u d y Sit e R e q uir e m e nt s  
8. 1  I n v e sti g at or / I n v e sti g ati o n Sit e S el e cti o n  
T h e r ol e of t h e P ri nci p al Inv esti g at or is t o i m pl e m e nt a n d m a n a g e t h e d ay -t o-d ay c o n d uct of t h e cli nic al 
i nv esti g ati o n as w ell as e ns ur e d at a i nt e grit y a n d t h e ri g hts, s af ety a n d w ell-b ei n g of t h e s u bj ects 
i nv olv e d i n t h e cli nic al i nv esti g ati o n. 
T h e pri nci p al i nv esti g at or /sit e s h all: 
•  
I nv esti g at or/sit e is q u alifi e d by tr ai ni n g, e d uc ati o n, a n d r el e v a nt ex p eri e nc e a p pr o pri at e t o t h e 
us e of t h e pr o d uct a n d ass oci at e d pr oc e d ur es ( S pi n al C or d Sti m ul ati o n)  
•  
I nv esti g at or/sit e ex p ects t o h a v e a d e q u at e ti m e a n d r es o urc es t o c o n d uct t h e st u dy t hr o u g h o ut 
t h e d ur ati o n of t h e st u dy ( u p t o 2 4-m o nt hs of f oll o w u p acti viti es)  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 5  of 1 1 7  
 
 
 
 
 
•  
I nv esti g at or/sit e h as acc ess t o a n a d e q u at e n u m b er of eli gi bl e s u bj ects ( e nr oll at l e ast 1 p ati e nt 
p er m o nt h)  
•  
I nv esti gat or/sit e h as t h e a bilit y t o c o m pl y wit h a p plic a bl e Et hics C o m mitt e e ( E C) a n d r e g ul at ory 
r e q uir e m e nts  
•  
I nv esti g at or is n ot d e b arr e d, dis q u alifi e d, or w or ki n g u n d er s a ncti o ns  
•  
Sit e h as a d e q u at e f aciliti es f or st u dy s u bj ects t o c o m pl et e st u dy ass ess m e nts  
•  
H as  a bilit y t o p erf or m fl u or osc o py/x -r a y wit h el ectr o nic o ut p ut 
8. 2  St u d y Sit e A cti v ati o n  
D uri n g t h e acti v ati o n pr oc ess ( pri or t o s u bj ect e nr oll m e nt), M e dtr o nic will tr ai n st u dy sit e p ers o n n el o n 
t h e C li nic al Inv esti g ati o n P l a n, r el ev a nt st a n d ar ds a n d r e g ul ati o ns, i nf or m e d c o ns e nt (I C), a n d d at a 
c oll ecti o n a n d r e p orti n g t o ols.  If n e w m e m b ers j oi n t h e st u dy sit e t e a m, t h e y will r ec eiv e tr ai ni n g o n t h e 
a p plic a bl e st u dy r e q uir e m e nts r el ev a nt t o t h eir r ol e b ef or e c o ntri b uti n g t o t h e st u dy.  
Pri or t o p erf or mi n g st u dy r el at e d acti viti es, all r e g ul at or y r e q uir e m e nts s h all b e f ulfill e d, i ncl u di n g, b ut 
n ot li mit e d t o t h e f oll o wi n g:  
•  
Et hics C o m mitt e e ( E C ) a p pr o v al ( a n d v oti n g list  w h e n a sit e t e a m m e m b er is a n E C m e m b er) 
of t h e c urr e nt v ersi o n of t h e CI P a n d I C.  
•  
E C  a p pr ov al  or ack n o wl e d g e m e nt of s u bj ect -f aci n g m at eri als a n d s u bj ect 
r ecr uit m e nt/ a dv ertisi n g (if a p plic a bl e) 
•  
R e g ul at ory A ut h orit y ( R A ) a p pr o v al or n otific ati o n , if a p plic a bl e  
•  
F ull y ex ec ut e d Cli nic al Tri al A gr e e m e nt ( C T A ) 
•  
Fi n a nci al discl os ur e  
•  
C V of i nv esti g at ors a n d k e y m e m b ers of t h e i nv esti g ati o n st u dy sit e t e a m ( as r e q uir e d).  T h e 
si g n at ur e o n t h e C V m ust b e d at e d wit hi n 3 y e ars pri or t o t h e d at e of acti v ati o n of t h e st u dy 
sit e.   
•  
D oc u m e nt ati o n of d el e g at e d t as ks  
•  
S p o ns or t ec h nic al s u p p ort list 
•  
D oc u m e nt ati o n of st u dy tr ai ni n g  ( a s e p ar at e tr ai ni n g d oc u m e nt will ov ervi e w t o pics a n d 
i ncl u d e d et ails o n t h e f or m at of d eli v er y i ncl u di n g t h e CI P, i nf or m e d c o ns e nt pr oc ess, d at a 
c oll ecti o n t o ols, r e g ul ati o ns a n d t h e d evic es) 
•  
A d diti o n al r e q uir e m e nts i m p os e d by l oc al r e g ul ati o ns, t h e E C a n d R A s h all b e f oll o w e d, if 
a p pr o pri at e.  
I n a d diti o n, all p artici p ati n g st u dy sit e st aff m ust b e tr ai n e d o n t h e c urr e nt v ersi o n of t h e CI P as w ell as 
o n t h e a p plic a bl e st u dy r e q uir e m e nts d e p e n di n g o n t h eir r ol e a n d m ust b e d el e g at e d by t h e P ri nci p al 
Inv esti g at or t o p erf or m st u dy r el at e d activiti es.   
M e dtr o nic will pr ovi d e e ac h st u dy sit e wit h d oc u m e nt ati o n of st u dy sit e/ Inv esti g at or r e a di n ess; t his 
l ett er m ust b e r ec eiv e d pri or t o p erf or mi n g st u dy r el at e d activiti es. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 6  of 1 1 7  
 
 
 
 
 
8. 3  R ol e of t h e S p o n s or R e pr e s e nt ati v e s  
I n a d diti o n t o p erf or mi n g m o nit ori n g a n d a u diti n g acti viti es, sp o ns or r e pr es e nt ati v es m a y pr o vi d e 
s u p p ort at t h e st u dy sit e as r e q uir e d f or t h e st u dy u n d er s u p ervisi o n of t h e Pri nci p al I nv esti g at or, 
i ncl u di n g: 
•  
Pr ovi d e st u dy  tr ai ni n g r el ev a nt a n d p erti n e nt t o t h e i nv olv e m e nt of p ers o n n el c o n d ucti n g 
st u dy acti viti es a n d i nv esti g at or r es p o nsi biliti es 
•  
T ec h nic al s u p p ort u n d er t h e s u p er visi o n of a st u dy Inv esti g at or, b ut n o d at a e ntry, s h all b e 
p erf or m e d by M e dtr o nic p ers o n n el or t h eir r e pr es e nt ati v es at st u dy sit es 
 
I n a d diti o n, f or t his st u dy, s p o ns or r e pr es e nt ativ es m ay b e a ut h oriz e d by t h e P ri nci p al Inv esti g at or t o 
p erf or m t h e f oll o wi n g si g nific a nt st u dy r el at e d d uti es:  
•  
S u p p ort st u dy Inv esti g at ors i n p erf or mi n g t h e st u dy  tri al a n d  i m pl a nt pr oc e d ur es i ncl u di n g 
d e vic e pr o gr a m mi n g, i nt err o g ati o ns a n d tr a ns missi o n of st u dy d at a  
•  
S u p p ort d at a c oll ecti o n d uri n g t h e tri al a n d i m pl a nt pr oc e d ur e a n d d evic e t esti n g  
•  
S u p p ort d at a c oll ecti o n d uri n g t h e st u dy visits   
•  
C o nt act s u bj ects t o tr o u bl es h o ot t h eir d e vic e s etti n gs 
•  
D u e t o ext e n u ati n g circ u mst a nc es, tr ai n e d M e dtr o nic p ers o n n el m ay r e m ot el y assist wit h 
i n-p ers o n t ec h nic al s u p p ort vi a liv e vi d e o str e a mi n g fr o m a s ec ur e a n d c o m pli a nt s er vic e.  
T h e li v e str e a m will n o t b e r ec or d e d a n d will b e acc essi bl e o nl y t o a ut h oriz e d s p o ns or 
t ec h nic al s u p p ort r e pr es e nt ati v e t hr o u g h a s ec ur e s ervic e d uri n g t h e visits 
 
A ny d at a c oll ecti o n c o m pl et e d by M e dtr o nic  p ers o n n el will b e cl e arly i d e ntifi e d as s uc h.  
9.  S el e cti o n of S u bj e ct s  
9. 1  St u d y P o p ul ati o n  
T h e i nt e n d e d st u dy p o p ul ati o n i ncl u d es  p ati e nts w h o ar e c a n di d at es f or u n d er g oi n g a S C S d e vic e tri al 
p er a p pr ov e d  i n dic ati o ns, exc e pt f or  p ati e nts i n dic at e d f or a n S C S d e vic e t o tr e at st a bl e i ntr act a bl e 
A n gi n a P ect oris or P eri p h er al V asc ul ar Dis e as e of F o nt ai n e St a g e III or hi g h er.  St u dy eli gi bilit y crit eri a 
m ust b e m et t o p artici p at e, s e e S ecti o n 9 . 
9. 2  S u bj e ct E nr oll m e nt  
W h e n a s u bj ect a n d t h e P ri nci p al Inv esti g at or or a ut h oriz e d d esi g n e e, as r e q uir e d, h a v e p ers o n ally 
si g n e d a n d d at e d t h e I nf or m e d C o ns e nt F or m (I CF) , t h e s u bj ect is c o nsi der e d a s u bj ect e nr oll e d i n t h e 
st u dy. T h e d at e t h e s u bj ect si g n e d t h e I CF a n d ot h er pri v ac y l a n g u a g e,  if a p plic a bl e m ust b e d oc u m e nt e d 
i n t h e s u bj ect’s m e dic al r ec or ds.  
S u bj ects will b e scr e e n e d t o e ns ur e t h ey m e et all  t h e i ncl usi o n a n d n o n e of t h e excl usi o n crit eri a pri or t o 
st u dy e nr oll m e nt. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 7  of 1 1 7  
 
 
 
 
 
9. 3  I n cl u si o n Crit eri a  
T h e p ati e nt m ust m e et f or t h e f oll o wi n g crit eri a t o b e i ncl u d e d i n t h e st u dy:  
1.  1 8 y e ars of a g e or ol d er  
2.  C a n di d at e  is u n d er g oi n g a M e dtr o nic S C S d e vic e tri al f or c hr o nic, i ntr act a bl e p ai n of t h e tr u n k 
a n d/ or li m bs  d u e t o F ail e d B ac k S ur g ery Sy n dr o m e  ( F BS S), C o m pl ex R e gi o n al P ai n Sy n dr o m e 
( C R P S), or  ot h er  c hr o nic n e ur o p at hic p ai n wit h o ut hist or y of s ur gic al i nt erv e nti o ns . 
N ot e:  T h e s p o ns or r ec o m m e n ds n ot e nr olli n g p ati e nts wit h c hr o nic p ai n d u e t o c o n diti o ns  t h at 
d o n ot h av e a d e q u at e evi d e nc e  t o s u p p ort t h e us e of S C S ( e. g., p ost-h e r p etic n e ur al gi a, f oc al 
C R PS etc.)   
3.  If b ei n g tr e at e d f or l o w-b ack a n d / or l e g p ai n,  
o  t h e b as eli n e o v er all^ V A S is ≥ 6 0 m m  a n d   
o  b as eli n e b ac k a n d/ or  l e g p ai n V A S is ≥6 0 m m .   
^ a v er a g e o v er all p ai n i n t h e b ac k  a n d /or l e g i n t h e 7 2 h o urs pri or t o  t h e b as eli n e visit, 
m e as ur e d usi n g V A S .  
4.  If b ei n g tr e at e d f or u p p er li m b p ai n, t h e b as eli n e V A S is ≥ 6 0 m m f or u p p er li m b p ai n. 
5.  O n st a bl e ( n o c h a n g e i n d os e, r o ut e, or fr e q u e ncy) pr escri b e d p ai n m e dic ati o ns b ei n g us e d f or 
b ac k a n d / or l e g p ai n or u p p er li m b p ai n, as d et er mi n e d by t h e I nv esti g at or, f or at l e ast 2 8 d ays 
pri or t o t h e d evic e tri al  
6.  Willi n g a n d a bl e t o pr o vi d e si g n e d a n d d at e d i nf or m e d c o ns e nt  
7.  Willi n g a n d a bl e t o c o m pl y wit h all st u dy pr oc e d ur es  
 
* T h e s p o n s o r st r o n gl y r e c o m m e n d s o nl y e n r olli n g p ati e nt s c a p a bl e of c o m p r e h e n di n g 
a n d c o n s e nti n g i n E n gli s h.  
 
9. 4  E x cl u si o n Crit eri a  
T h e p ati e nt m ust n ot m e et a ny of t h e f oll o wi n g crit eri a t o b e i ncl u d e d i n t h e st u dy:  
1.  I n dic at e d f or a n S C S d evic e t o tr e at st a bl e i ntr act a bl e A n gi n a P ect oris, P eri p h er al V asc ul ar 
Dis e as e of F o nt ai n e St a g e III or hi g h er , or Di a b etic P eri p h er al N e ur o p at hy  
2.  Pr evi o usly tri al e d or i m pl a nt e d wit h a s pi n al c or d sti m ul at or, p eri p h er al or v a g us n er v e 
sti m ul at or, d e e p br ai n sti m ul at or,  or a n i m pl a nt a bl e i ntr at h ec al dr u g d eli v ery syst e m  
3.  C urr e ntl y p artici p ati n g, or pl a ns t o p artici p at e, i n a n ot h er i nv esti g ati o n al st u dy u nl ess writt e n 
a p pr o v al is pr ovi d e d by t h e M e dtr o nic st u dy t e a m  
4.  M aj or ps yc hi atric c o m or bi dit y or ot h er pr o gr essiv e dis e as e t h at m ay c o nf o u n d st u dy r es ults, as 
d et er mi n e d by t h e I nv esti g at or  
5.  S eri o us dr u g -r el at e d b e h avi or al iss u es ( e. g., alc o h ol d e p e n d e nc y, ill e g al s u bst a nc e a b us e), as 
d et er mi n e d by t h e I nv esti g at or  
N ot e: T h e  S p o ns or r ec o m m e n ds excl u di n g p ati e nts  o n ≥1 0 0 M M E of o pi oi ds/ d ay.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 3 8  of 1 1 7  
 
 
 
 
 
6.  Pr e g n a nt or pl a n ni n g o n b ec o mi n g pr e g n a nt (if f e m al e a n d s ex u all y activ e, s u bj ect m ust b e usi n g 
a r eli a bl e f or m of birt h c o ntr ol, b e s ur gic all y st eril e, or b e at l e ast 2 y e ars p ost -m e n o p a us al)  
7.  B e i nv ol v e d i n a n i nj ur y cl ai m or u n d er c urr e nt liti g ati o n  
N ot e: t his i ncl u d es p ati e nts t h at ar e t h e b e n efici ar y of a s ucc essf ul i nj ur y cl ai m. 
1 0.  St u d y Pr o c e d ur e s  
1 0. 1  S c h e d ul e of E v e nt s  
Fi g ur e 5  a n d Fi g ur e 6  ar e  fl o w di a gr a ms of h o w s u bj ects will c o m pl et e t h e st u dy.  
  
 
Fi g ur e 5 : St u d y Fl o w Di a gr a m 
 
Fi g ur e 6 : I n-Cli ni c T e sti n g Fl o w Di a gr a m  
1 0. 2  D at a C oll e cti o n  
D at a c oll ecti o n r e q uir e m e nts ar e s u m m ariz e d i n T a bl e 5  b el o w.  
T a bl e 5 : D at a c oll ecti o n a n d st u d y pr oc e d ur e r e q uir e m e nts at s u bj ect visits 
St u d y Pr oc e d ur es, 
T as ks a n d D at a 
C oll ecti o n  
E nr oll m e n
t/ B as eli n e 
D e vic e 
Tri al  
Tri al 
L e a d 
E x pl a nt  
I nc e pti v 
I m pl a nt 
P h o n e 
C alls 6 
D e vic e 
Acti v ati
o n  
D e vic e 
O pti miz ati o n 
( W e e ks 1-4)  
R a n d o miz ati o n 
a n d I n -Cli nic 
T esti n g  
 Visits 3 -, 6-, 1 2-, 
1 8 -, a n d 2 4-
M o nt h s 
U nsc h e d ul e d  S yst e m 
M o dific ati o n  
I nf or m e d 
C o ns e nt 
Pr oc ess  
X 
 
 
 
 
 
 
 
 
 
 
Psyc h ol o gic al 
E v al u ati o n  
X 
 
 
 
 
 
 
 
 
 
 
M RI or X -R a y  
X 1 
 
 
 
 
 
 
 
 
 
 
I ncl usi o n/ Excl us
i o n Ass ess m e nt 
X 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 5 . 0 
P a g e 3 9  of 1 1 7  
 
 
 
 
 
St u d y Pr oc e d ur es, 
T as ks a n d D at a 
C oll ecti o n  
E nr oll m e n
t/ B as eli n e 
D e vic e 
Tri al  
Tri al 
L e a d 
E x pl a nt  
I nc e pti v 
I m pl a nt 
P h o n e 
C alls 6 
D e vic e 
Acti v ati
o n  
D e vic e 
O pti miz ati o n 
( W e e ks 1-4)  
R a n d o miz ati o n 
a n d I n -Cli nic 
T esti n g  
 Visits 3 -, 6-, 1 2-, 
1 8 -, a n d 2 4-
M o nt h s 
U nsc h e d ul e d  S yst e m 
M o dific ati o n  
D e m o gr a p hics 
a n d M e dic al 
Hist ory  
X 
 
 
 
 
 
 
 
 
 
 
P ai n 
M e dic ati o ns  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
V A S  
X  
 
 
 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Fl u or osc o py/ X -
R a y  
 
X 
 
X 
 
 
 
 
 
X 5 
X 5 
D evic e 
I nf or m ati o n 
 
X 
 
X 
 
 
 
 
 
 
 
D evic e D at a  
 
X  
X  
X  
 
X  
X  
X  
X  
X  
X  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
R a n d o miz ati o n 
Pr oc ess  
 
 
 
 
 
 
 
X 
X 7 
 
 
Al g orit h m S et -
U p P ar a m et ers  
 
 
 
 
 
 
 
X 
X 7 
 
 
E C A P r ec or di n gs  
 
 
 
 
 
 
 
X  
X 7 
 
 
S u bj ect R ati n g 
of Sti m ul ati o n 
S e ns ati o n wit h 
Lik ert Sc al e 
 
 
 
 
 
 
 
X 
X 7 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
A dv ers e E v e nts 
( A Es) 
As t h ey occ ur  
D evic e 
D efici e ncy ( D D)  
As t h ey occ ur  
St u dy 
D evi ati o ns  
As t h ey occ ur  
1O pti o n al  
2F or s u bj ects wit h l o w -b ack a n d / or l e g p ai n 
3I n s u bj ects wit h u p p er li m b p ai n 
4F or s u bj ects wit h n eck p ai n  
5If n ec ess ary 
6E v ery  w e ek st arti n g aft er D evic e Acti v ati o n  t hr o u g h t h e 3-M o nt h V isit a n d m o nt hly t h er e aft er exc e pt f or t h e m o nt hs w h e n t h e s u bj ect h as a 
st u dy r e q uir e d visit 
7At t h e 3- a n d 1 2 - Mo nt h  Visits o nly 
8At t h e 3 -, 1 2-, a n d 2 4 - Mo nt h V isits o nly 
9St arti n g at t h e e n d of t h e D evic e Acti v ati o n  visit t hr o u g h t h e 2 4 - Mo nt h V isit 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 0  of 1 1 7  
 
 
 
 
 
6E v ery  w e ek st arti n g aft er D evic e Acti v ati o n  t hr o u g h t h e 3-M o nt h V isit a n d m o nt hly t h er e aft er exc e pt f or t h e m o nt hs w h e n t h e s u bj ect h as a 
st u dy r e q uir e d visit 
7At t h e 3- a n d 1 2 - Mo nt h V isits o nly 
8At t h e 3 -, 1 2-, a n d 2 4 - Mo nt h V isits o nly 
9St arti n g at t h e e n d of t h e D evic e Acti v ati o n  visit t hr o u g h t h e 2 4 - Mo nt h V isit 
 
1 0. 3  S c h e d ul e d Vi sit Wi n d o w s  
M e dtr o nic will pr ovi d e t h e t ar g et d at es a n d wi n d o ws f or e ac h visit t o t h e st u dy sit e , as  a p plic a bl e. 
S h o ul d a s u bj ect miss a visit or t h e visit f all o utsi d e t h e pr e -s p ecifi e d wi n d o w, a st u dy d evi ati o n m ust b e 
r e p ort e d a n d t h e ori gi n al visit  sc h e d ul e m ai nt ai n e d f or s u bs e q u e nt visits.  A l at e visit is pr ef err e d ov er a 
miss e d visit b ut m ust b e a cc o m p a ni e d by a st u dy d evi ati o n.  V isit wi n d o ws ar e list e d i n T a bl e 6 . 
T a bl e 6 : D at a c oll ecti o n a n d st u d y pr oc e d ur e r e q uir e m e nts at s u bj ect visits 
Visit  
Visit r a n g es  
E nr oll m e nt/ B as eli n e  
N ot a p plic a bl e  
D evic e Tri al  
≤ 2 8  d a ys aft er E nr oll m e n t/ B as eli n e 
D evic e Tri al P h o n e C alls  
D ail y , as n e e d e d 
D evic e Tri al L e a d Ex pl a nt  
≤ 1 0 d a ys fr o m D e vic e Tri al  
S C S I m pl a nt  
≤ 6 0 d a y s aft er e n d of D evic e T ri al 
P h o n e C alls  
W e ekl y st arti n g aft er D evic e Activ ati o n  t hr o u g h t h e 3-M o nt h 
V isit a n d m o nt hly t h er e aft er wit h a n exc e pti o n f or t h e w e e k s or 
m o nt hs w h e n t h e s u bj ect h as a st u dy r e q uir e d visit.  
D evic e Acti v ati o n  ( D ay 0) 
9 -1 6  d a ys aft er  i m pl a nt: p e n di n g w o u n d h e ali n g 
 
 
 
 
 
 
R a n d o miz ati o n a n d I n-cli nic 
T esti n g   
3 0 d ays ± 5 d a ys fr o m D a y 0  (visit m ay occ ur o n t h e s a m e d ay as 
Visit 4 if Visit 4 is occ urri n g wit hi n wi n d o w, a n d at t h e discr eti o n 
of t h e PI ) 
3 -M o nt h  
9 0 d ays ± 1 5 d ays fr o m D ay 0  
6 -M o nt h  
1 8 0 d a ys ± 1 5 d a ys fr o m D ay 0  
1 2 -M o nt h  
3 6 0  d a ys ± 3 0  d a ys fr o m D ay 0  
1 8 -M o nt h  
5 4 0  d a ys ± 3 0  d a ys fr o m D ay 0  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 1  of 1 1 7  
 
 
 
 
 
Visit  
Visit r a n g es  
2 4 -M o nt h  
7 2 0  d a ys ± 3 0  d a ys fr o m D ay 0  
1 0. 4  Pri or a n d C o n c o mit a nt M e di c ati o n s  
O nl y pr escri b e d m e dic ati o ns us e d f or t h e tr e at m e nt of l o w-b ac k , l e g p ai n a n d u p p er li m b p ai n  will b e 
c oll ect e d d uri n g t h e st u dy.  
 
  A ny c h a n g es t o s u bj ect’s p ai n m e dic ati o ns w hil e t h e y ar e e nr oll e d i n t h e st u dy will b e 
d oc u m e nt e d i n t h e s u bj ect’s m e dic al r ec or ds a n d t h e st u dy d at a b as e .  
 
 
  
All m e dic ati o ns us e d t o tr e at a dv ers e e v e nts (r e g ar dl ess of t h eir r e as o n pr escri b e d) will b e d oc u m e nt e d 
o n a n e C R F . 
1 0. 5  S u bj e ct C o n s e nt  
I nf or m e d c o ns e nt is d efi n e d as a l e g ally eff ectiv e d oc u m e nt e d c o nfir m ati o n of a s u bj ect’s v ol u nt ar y 
a gr e e m e nt t o p artici p at e i n a p artic ul ar st u dy aft er i nf or m ati o n h as b e e n gi v e n a n d ex pl ai n e d t o t h e 
s u bj ect o n all as p ects of t h e st u dy t h at ar e r el e v a nt t o t h e s u bj ect’s d ecisi o n t o p ar tici p at e.  T his pr oc ess 
i ncl u d es o bt ai ni n g a n I C f or m a n d ot h er pri v acy l a n g u a g e as r e q uir e d by l a w t h at h as b e e n a p pr o v e d by 
t h e st u dy sit e’s E C a n d si g n e d a n d d at e d by t h e s u bj ect. A s u bj ect m a y o nl y c o ns e nt aft er i nf or m ati o n 
h as b e e n giv e n a n d ex pl ai n e d  t o t h e s u bj ect o n all as p ects of t h e cli nic al i nv esti g ati o n t h at ar e r el ev a nt 
t o t h e s u bj ect’s d ecisi o n t o p artici p at e.  
Pri or t o e nr olli n g s u bj ects, t h e I C  a n d ot h er pri v acy l a n g u a g e as r e q uir e d by l a w m ust b e a p pr ov e d by 
t h e E C.  T h e d oc u m e nt(s) m ust b e c o ntr oll e d (i. e., v ersi o n e d a n d d at e d) t o e ns ur e it is cl e ar w hic h 
v ersi o n(s) w er e a p pr ov e d by t h e E C.  A ny a d a pt ati o n of t h e s a m pl e I C m ust b e r evi e w e d a n d a p pr o v e d 
by M e dtr o nic a n d t h e E C r evi e wi n g t h e a p plic ati o n pri or t o e nr olli n g s u bj ects.  
T h e i nv es ti g at or m ust n otify t h e s u bj ect of a ny si g nific a nt n e w fi n di n gs a b o ut t h e st u dy t h at b ec o m e 
av ail a bl e d uri n g t h e c o urs e of t h e st u dy w hic h ar e p erti n e nt t o t h e s af et y a n d w ell -b ei n g of t h e s u bj ect, 
as t his c o ul d i m p act a s u bj ect’s willi n g n ess t o p artici p at e i n t h e st u dy. If r el e v a nt, c o ns e nt m a y b e 
r e q u est e d fr o m s u bj ects t o c o nfir m t h eir c o nti n u e d p artici p ati o n. 
T h e t e m pl at e I C will b e pr ovi d e d u n d er s e p ar at e c o v er.  
Pri or t o i niti ati o n of a ny st u dy -s p ecific pr oc e d ur es, I C m ust b e o bt ai n e d fr o m t h e s u bj ect.  Li k e wis e, 
priv ac y or h e alt h i nf or m ati o n pr ot ecti o n r e g ul ati o n m a y r e q uir e s u bj ects t o si g n a d diti o n al f or ms t o 
a ut h oriz e st u dy sit es t o s u b mit s u bj ect i nf or m ati o n t o t h e st u dy s p o ns or. T h e I C pr oc ess m ust b e 
c o n d uct e d by t h e P ri nci p al Inv esti g at o r or a n a ut h oriz e d d esi g n e e, a n d t h e I C F or m a n d ot h er pri v acy 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 2  of 1 1 7  
 
 
 
 
 
l a n g u a g e as r e q uir e d by l a w m ust b e gi v e n t o t h e s u bj ect i n a l a n g u a g e h e/s h e is a bl e t o r e a d a n d 
u n d erst a n d. T h e pr oc ess of I C m ust b e c o n d uct e d wit h o ut usi n g c o erci o n or u n d u e i m pr o p er i nfl u e nc e 
o n or i n d uc e m e nt of t h e s u bj ect t o p artici p at e by t h e i nv esti g at or or ot h er st u dy sit e p ers o n n el.   T h e I C 
pr oc ess s h all n ot w ai v e or a p p e ar t o w aiv e s u bj ect’s l e g al ri g ht.  T h e l a n g u a g e us e d s h all b e as n o n -
t ec h nic al as p ossi bl e a n d m ust b e u n d erst a n d abl e t o t h e s u bj ect a n d t h e i m p arti al wit n ess, w h er e 
a p plic a bl e.  
T h e s u bj ect m ust h av e a m pl e ti m e a n d o p p ort u nit y t o r e a d a n d u n d erst a n d t h e I C f or m, t o i n q uir e a b o ut 
d et ails of t h e st u dy, a n d t o d eci d e w h et h er or n ot t o p artici p at e i n t h e st u dy.  All q u es ti o ns a b o ut t h e 
st u dy s h o ul d b e a ns w er e d t o t h e s atisf acti o n of t h e s u bj ect. 
W h e n t h e s u bj ect d eci d es t o p artici p at e i n t h e st u dy, t h e I C m ust b e si g n e d a n d p ers o n ally d at e d by t h e 
s u bj ect a n d Inv esti g at or or a ut h oriz e d d esi g n e e, as r e q uir e d by t h e I C, a n d  e ns ur e d by t h e P ri nci p al 
Inv esti g at or or his/ h er a ut h oriz e d d esi g n e e.  If a p plic a bl e, i n d e p e n d e nt wit n ess m ust b e pr es e nt 
t hr o u g h o ut t h e e ntir e i nf or m e d c o ns e nt pr oc ess, a n d t h e writt e n i nf or m e d c o ns e nt f or m a n d a ny ot h er 
i nf or m ati o n r el at e d t o t h e st u dy m ust b e r e a d al o u d a n d ex pl ai n e d t o t h e pr os p ecti v e s u bj ect. If 
a p plic a bl e, wit n ess s h all als o si g n a n d p ers o n all y d at e t h e c o ns e nt f or m t o att est t h at t h e i nf or m ati o n i n 
t h e I C F or m w as acc ur at el y ex pl ai n e d a n d cl e arl y u n d erst o o d by t h e s u bj ect, a n d t h at i nf or m e d c o ns e nt 
w as fr e el y giv e n.  
A c o py of t h e I C a n d ot h er pri v ac y l a n g u a g e, si g n e d a n d d at e d as r e q uir e d by l a w, m ust b e pr o vi d e d t o 
t h e s u bj ect.  
If t h e I C is o bt ai n e d t h e s a m e d ay t h e s u bj ect b e gi ns p artici p ati n g i n st u dy-r el at e d pr oc e d ur es, it m ust 
b e d oc u m e nt e d i n t h e s u bj ect’s c as e hist or y t h at c o ns e nt w as o bt ai n e d pri or t o p artici p ati o n i n a ny 
st u dy-r el at e d pr oc e d ur es.  It is b est pr actic e f or t h e I C pr oc ess t o b e d oc u m e nt e d i n t h e s u bj ect’s c as e 
hist or y, r e g ar dl ess of circ u mst a nc e.   I n t h e ev e nt t h e s u bj ect c a n n ot r e a d a n d/ or writ e, a wit n ess e d 
(i m p arti al t hir d p art y) I C F or m will b e all o w e d, pr ovi d e d d et ail e d d oc u m e nt ati o n of t h e pr oc ess is 
r ec or d e d i n t h e s u bj ect’s c as e hist or y a n d t h e wit n ess si g ns a n d d at es t h e I C F or m. I n t h e ev e nt t h e 
s u bj ect c a n n ot r e a d a n d/ or writ e, t h e I C pr oc ess s h all b e o bt ai n e d t hr o u g h a s u p er vis e d or al pr oc ess if 
t h e l oc al r e g ul ati o n all o ws. A n i n d e p e n d e nt a n d i m p arti al wit n ess m ust b e pr es e nt d uri n g t his pr oc ess. 
T h e I C a n d a ny ot h er i nf or m ati o n m ust b e r e a d al o u d t o t h e pr os p ecti v e s u bj ect. W h e n ev er p ossi bl e, 
eit h er t h e s u bj ect s h all si g n a n d p ers o n ally d at e t h e i nf or m e d c o ns e nt f or m. T h e wit n ess si g ns a n d 
p ers o n all y d at es t h e I C att esti n g t h at t h e i nf or m ati o n w as acc ur at ely ex pl ai n e d a n d t h at i nf or m e d 
c o ns e nt w as fr eely giv e n.  
T h e ori gi n al of t h e si g n e d I C m ust b e fil e d i n t h e h os pit al/cli nic al c h art a n d/ or wit h t h e s u bj ect’s st u dy 
d oc u m e nts.  
T h e I C a n d ot h er pri v acy l a n g u a g e as r e q uir e d by l a w m ust b e a v ail a bl e f or m o nit ori n g a n d a u diti n g.  A ny 
M e dtr o nic Fi el d p ers o n n el w h o s u p p ort t h e st u dy pr oc e d ur e m ust b e a bl e t o r evi e w t h e s u bj ect’s si g n e d 
a n d d at e d I C a n d v erify its c o m pl et e n ess pri or t o pr oc e e di n g wit h t h e i m pl a nt/ d o w nl o a d.  I n t h e ev e nt 
t h e M e dtr o nic Fi el d p ers o n n el i d e ntif y I C as b ei n g i nc o m pl et e, t h e st u dy pr oc e d ur e will n ot b e all o w e d 
t o occ ur u ntil t h e c o ns e nt of t h e s u bj ect c a n b e a d e q u at el y a n d a p pr o pri at ely o bt ai n e d.  
1 0. 6  E nr oll m e nt  
A s u bj ect is c o nsi d er e d e nr oll e d w h e n t h e s u bj ect a n d t h e Pri nci p al I nv esti g at or or a ut h oriz e d d esi g n e e, 
i m p arti al wit n ess, as r e q uir e d, h a v e p ers o n all y si g n e d a n d d at e d t h e i nf or m e d c o ns e nt.  T h e d at e t h e 
s u bj ect si g n e d t h e i nf or m e d c o ns e nt f or m, as r e q uir e d by l a w, m ust b e d oc u m e nt e d i n t h e s u bj ect’s 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 3  of 1 1 7  
 
 
 
 
 
m e dic al r ec or ds.  A l o g of all s u bj ects e nr oll e d i n t h e st u dy s h o ul d b e m ai nt ai n e d.   E nr oll m e nt c a n b e a 
st a n d-al o n e visit or c a n occ ur o n t h e s a m e d ay as scr e e ni n g.  O nc e c o ns e nt is o bt ai n e d, r e p ort a dv ers e 
e v e nts/ d e at hs, st u dy d evi ati o ns a n d s u bj ect exits as t h e y occ ur.   N o st u dy -r el at e d pr oc e d ur es or t esti n g 
m a y b e c o n d uct e d pri or t o c o m pl eti o n of t h e i nf or m e d c o ns e nt pr oc ess wit h a s u bj ect.  
1 0. 7  Pr e -Pr o c e d ur e  Scr e e ni n g  
F oll o wi n g e nr oll m e nt, p erf or m a psyc h ol o gic al ex a mi n ati o n t o e ns ur e t h e s u bj ect d o es n’t h av e a ny 
ps yc hi atric c o m or bi dit i es t h at c o ul d i nfl u e nc e t h e a bilit y t o h av e a p er m a n e nt  S CS d e vic e.  Alt er n ati v ely, 
t h e r es ults of a psyc h ol o gic al ex a mi n ati o n p erf or m e d i n t h e l ast 6 m o nt hs pri or t o e nr oll m e nt i n t h e 
st u dy c a n b e us e d aft er t h e m e dic al pr of essi o n al r ec o nfir ms s u bj ect s uit a bilit y f or r ec eivi n g a S C S 
s yst e m. P erf or m a n  x-r a y, C T sc a n, or M RI, t o c o nfir m a p er m a n e nt  i m pl a nt is a p pr o pri at e.  A n existi n g  x-
r a y, C T sc a n, or M RI c a n b e us e d f or t his p ur p os e, u nl ess t h e i nv esti g at or d e e ms u p d at e d i m a gi n g is 
n e e d e d .  Exit t h e s u bj ect fr o m t h e st u dy a n d c o m pl et e a n Exit e C R F if t h e s u bj ect is n ot s uit a bl e t o m ov e 
o n  t o a d e vic e tri al. 
1 0. 8  B a s eli n e  
U p t o 1 4 0 s u bj ects will b e e nr oll e d i n t h e st u dy t o e ns ur e u p t o 5 7 s u bj ects wit h l o w-b ac k a n d / or l e g 
p ai n a n d u p t o 1 2 s u bj ects wit h u p p er li m b a n d/ or n eck  p ai n  ar e i m pl a nt e d  wit h t h e st u dy d e vic e .  Of 
t h e 5 7  s u bj ects wit h l o w-b ac k a n d/ or l e g p ai n, it is r ec o m m e n d e d t h at at l e ast 2 5 of t h os e s u bj ects h a v e 
a b as eli n e b ack V A S ≥ 6 0 m m.  Ass ess a n d c o nfir m eli gi bilit y t o t h e st u dy -s p ecific i ncl usi o n/ excl usi o n 
crit eri a.  E ac h s u bj ect m ust b e i n c o m pli a nc e wit h all of t h e i ncl usi o n/ excl usi o n crit eri a t o b e eli gi bl e t o 
p artici p at e i n t his st u dy.  If it is d et er mi n e d t h at a s u bj ect is i n eli gi bl e f or t h e st u dy, or if t h e y wit h dr a w 
e arl y, a st u dy exit m ust b e r ec or d e d  i n t h e st u dy d at a b as e.  St u dy ass ess m e nts will b e c o m pl et e d a n d 
activity g o als will b e c oll ect e d .  
 
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e b as eli n e vi sit: 
•  
I ncl usi o n/ excl usi o n crit eri a 
•  
D e m o gr a p hics  
•  
M e dic al hist ory  
•  
P ai n m e dic ati o ns  
•  
V A S  
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 4  of 1 1 7  
 
 
 
 
 
1 0. 9  D e vi c e Tri al  
S u bj ects will b e i m pl a nt e d  wit h t w o p erc ut a n e o us l e a ds  a n d t h e ext eri oriz e d pr oxi m al e n d will b e 
c o n n ect e d t o a wir el ess ext er n al n e ur osti m ul at or. T h e s u bj ect m a y  p erf or m a fl exi o n m a n e uv er  pri or t o 
h avi n g  fl u or osc o py/x-r a y p erf or m e d of t h e l e a d l oc ati o n.  T h e tri al p h as e is n ot t o exc e e d 1 0 d ays.   
S u bj ects will b e c o nt act e d vi a p h o n e d uri n g t his p h as e r e g ar di n g t h eir d e vic e tri al.  
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e d e vic e tri al vis it: 
•  
Fl u or osc o py/x -r ay of tri al l e a d l oc ati o n  
•  
D evic e i nf or m ati o n f or tri al pr o d ucts  
•  
C oll ect d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic  
•  
P ai n m e dic ati o n  c h a n g es 
•  
A Es/ d evic e d efici e nci es  
1 0. 1 0  
I m a gi n g  
A nt eri or/ p ost eri or a n d l at er al i m a g es, e. g. , x-r a y or fl u or osc o py, of t h e tri al l e a d(s) will b e t a k e n, 
i ncl u di n g at l e ast o n e a nt eri or/ p ost eri or i m a g e t h at c a pt ur es t h e v ert e br al l e v el of t h e l e a d(s).  A n 
a d diti o n al i m a g e of t h e ext er n aliz ati o n of t h e l e a d(s) m a y als o b e r e q uir e d f or t h e d e vic e tri al (f or 
ex a m pl e, if n ot visi bl e i n t h e ot h er i m a g es).   T h e s u bj ect m ay  p erf or m a fl exi o n m a n e uv er pri or t o 
h avi n g fl u or osc o py/x -r a y p erf or m e d of t h e l e a d l oc ati o n.  S e n d t h e r e d act e d i m a g es t o M e dtr o nic  
f oll o wi n g all r e q uir e d ti m e p oi nts . 
1 0. 1 1  
D e vi c e Tri al  L e a d  E x pl a nt 
All s u bj ects will h av e t h eir d e vic e i nt err o g at e d.  All r e p orts (fi n al) will b e c oll ect e d a n d l e a ds will b e 
ex pl a nt e d.  Tri al l e a d ex pl a nt m ust occ ur o n or b ef or e 1 0 d ays fr o m t h e tri al i m pl a nt.   S u bj ects w h o h a v e 
5 0 % or gr e at er r e d ucti o n  i n p ai n will g o o nt o a p er m a n e nt I N S i m pl a nt i n t h e st u dy.  If n ot, exit t h e 
s u bj ect fr o m t h e st u dy. 
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e tri al l e a d ex pl a nt visit:  
 
  
•  
C oll e ct d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic  
•  
P ai n m e dic ati o n  c h a n g es 
•  
A Es/ d evic e d efici e nci es  
1 0. 1 2  
I n c e pti v  I m pl a nt  
S u bj ects will b e i m pl a nt e d wit h t h e I nc e ptiv I N S d evic e a n d t w o p erc ut a n e o us l e a ds .  U p t o t hr e e l o w-
b ac k a n d / or l e g p ai n s u bj ects m a y b e i m pl a nt e d wit h a s ur gic al l e a d.  If p ossi bl e, t h e s u bj ect m ay  
p erf or m a fl exi o n m a n e uv er pri or t o h avi n g fl u or osc o py/x -r ay p erf or m e d of t h e l e a d l oc ati o n.   
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e I N S  i m pl a nt: 
•  
D evic e i nf or m ati o n  f or i m pl a nt e d pr o d ucts 
•  
Fl u or osc o py/x -r ay i m a g es of fi n al l e a d l oc ati o n  
•  
C oll ect d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic  
•  
P ai n m e dic ati o n  c h a n g es 
•  
A Es/ d evic e d efici e nci es  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 5  of 1 1 7  
 
 
 
 
 
 
1 0. 1 3  
D e vi c e  A cti v ati o n  
T h e d evic e activ ati o n visit will t a k e pl ac e 9 -1 6 d a ys aft er i m pl a nt, p e n di n g w o u n d h e ali n g.  R esc h e d ul e 
t h e visit if t h e w o u n d h as n ot h e al e d.  Pr o gr a m mi n g will  c o nsist of t h er a py a n d N e ur o S e ns e f or s u bj ects 
w h o h av e a m e as ur a bl e E C A P.   S u bj ec ts will b e e d uc at e d o n t h e us e of t h eir h a n ds et  a n d r ec h ar g er.  
Pr ovi d e t h e s u bj ect t h e sti m ul ati o n di ar y at t h e e n d of t his visit. 
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e d e vic e acti v ati o n  visit: 
•  
C oll ect d at a fil es vi a t h e cli nici a n p r o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic 
•  
P ai n m e dic ati o n  c h a n g es 
•  
A Es/ d evic e d efici e nci es  
 
  
 
 
   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
1 0. 1 5  
R a n d o mi z ati o n a n d I n -Cli ni c T e sti n g  
I n-Cli nic T esti n g will occ ur wit hi n 3 0 d a ys ± 5 d ays fr o m  D evic e Activ ati o n a n d a g ai n at t h e 3- a n d 1 2 -
M o nt h  Visits.  A cl e ar a n d m e as ur a bl e E C A P m ust b e pr es e nt  i n or d er t o b e r a n d o miz e d d uri n g  i n-cli nic 
t esti n g. Su bj ects will b e r a n d o miz e d t o eit h er N e ur o S e ns e O n f oll o w e d by N e ur o S e ns e Off i n -cli nic 
t esti n g, or N e ur o S e ns e Off f oll o w e d by N e ur o S e ns e O n t esti n g.  T h e s u bj ect will b e bli n d e d t o t h e 
s etti n gs t est e d.  
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d d uri n g t h e i n -cli nic t esti n g visit: 
•  
 
•  
R a n d o miz ati o n assi g n m e nt  
•  
S u bj ect r ati n g of sti m ul ati o n s e ns ati o n wit h Li k ert sc al e  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 6  of 1 1 7  
 
 
 
 
 
 
 
 
  
•  
C oll e ct d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic  
•  
P ai n m e dic ati o ns  
•  
A Es/ d evic e d efici e nci es  
 
 
 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 0. 1 5. 2  
M et h o d s of A s si g ni n g S u bj e ct s t o Tr e at m e nt Gr o u p s  
S u bj ects w h o pr o vi d e cl e ar, m e as ur a bl e E C A Ps at i n-cli nic t esti n g s et u p will b e r a n d o miz e d t o r ec ei v e 
eit h er  N e ur o  Se ns e O n  f oll o w e d by N e ur o  Se ns e Off  t esti n g or N e ur o  Se ns e Off  f oll o w e d by N e ur o  Se ns e 
O n  t esti n g i n a 1: 1 r ati o, str atifi e d by st u dy sit e.  
P er m ut e d bl oc ks (siz e 2 a n d 4) w ill b e us e d t o g e n er at e t h e r a n d o miz ati o n assi g n m e nts i n or d er t o 
b al a nc e t h e s u bj ects r ec ei vi n g e ac h tr e at m e nt assi g n m e nt.  R a n d o miz ati o n all oc ati o n will b e  c o nc e al e d 
fr o m t h e s u bj ect, usi n g a c e ntr aliz e d a ut o m atic w e b-b as e d d at a m a n a g e m e nt syst e m.  O nc e assi g n e d, 
t h e r a n d o miz ati o n assi g n m e nt f or t h e s u bj ect c a nn ot b e c h a n g e d  f or t h at visit.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 7  of 1 1 7  
 
 
 
 
 
1 0. 1 5. 3  
Bli n di n g  
T h e i n-cli nic t esti n g p h as e  of t h e  st u dy will b e si n gl e bli n d e d t o r e d uc e bi as. T h e s u bj ect  will n ot h a v e 
k n o wl e d g e of t h e t h er a py assi g n e d d uri n g t h e i n-cli nic t esti n g p h as e s of t h e st u dy . It is ess e nti al t h at 
st u dy sit es t ak e s p eci al pr ec a uti o n t o m ai nt ai n t h e bli n d d uri n g t h e i n-cli nic t esti n g. It is r ec o m m e n d e d 
t h at r ec or ds a n d pri nt o uts t h at discl os e t h e s u bj ect’s r a n d o miz ati o n assi g n m e nt b e k e pt i n t h e m e dic al 
r ec or d a n d/ or st u dy fil e i n e nv el o p es, s o as t o pr ot ect t h e bli n d e d st at us. Ot h er o pti o ns t o m ai nt ai n t h e 
bli n di n g m a y b e a p pli e d p er i nv esti g ati o n al st u dy si t e r es e arc h pr oc e d ur e. 
M e dtr o nic p ers o n n el  will b e u n bli n d e d  t o r a n d o miz ati o n assi g n m e nts. 
1 0. 1 5. 4  
Cr o s s o v er  
Cr oss o v er f or t his st u dy visit  is d efi n e d as t h e s u bj ects r ec eiv e eit h er N e ur o S e ns e O n f oll o we d  by N e ur o 
S e ns e Off t esti n g, or N e ur o S e ns e Off f oll o w e d by  N e ur o S e ns e O n t esti n g. All r a n d o miz e d s u bj ects will 
cr oss o v er d uri n g t h e i n -cli nic t esti n g.  
 
 
 
 
 
  
E v ery r e as o n a bl e eff ort s h o ul d b e m a d e t o pr e v e nt u n bli n di n g of t h e s u bj ect . 
1 0. 1 6  
S c h e d ul e d Vi sit s  
S u bj ects will b e s e e n at 3 -, 6-, 1 2-, 1 8-, a n d 2 4 - Mo nt hs.  
1 0. 1 6. 1  
3- , 6-, 1 2-, 1 8-, a n d 2 4 -M o nt h Vi sit s 
It is str o n gl y r ec o m m e n d e d t o pr o gr a m  t h e S C S d evic e wit h N e ur o S e ns e O n d uri n g t h e f oll o w -u p p h as e .   
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d at t h e visit s: 
•  
 
 
•  
V A S  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 8  of 1 1 7  
 
 
 
 
 
 
 
•  
C oll ec t d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic 
•  
P ai n m e dic ati o n c h a n g es  
•  
A Es/ d evic e d efici e nci es  
 
1 0. 1 7  
P h o n e C all s  
S u bj ects will b e c all e d ev ery w e e k st arti n g aft er D evic e Activ ati o n  t hr o u g h t h e 3-M o nt h Visit a n d 
m o nt hl y t h er e aft er wit h a n exc e pti o n f or t h e w e eks or m o nt hs w h e n t h e s u bj ect h as a st u dy r e q uir e d 
visit. If t h e s u bj ect r e p orts b ei n g U ns atisfi e d wit h t h e t her a py, as d et er mi n e d by t h e p h o n e c all, t h e 
s u bj ect m a y b e br o u g ht  i n f or a n U nsc h e d ul e d visit f or f urt h er t h er a py o pti miz ati o n. 
 
 
  
 
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d d uri n g t h e p h o n e c alls:  
•  
P ai n R eli ef  St at us  
 
 
o  P ai n sc or e o n t h e 1 1 -p oi nt N u m eric R ati n g Sc al e ( N R S) of 0 - 1 0; 0 b ei n g n o p ai n a n d 
1 0 b ei n g w orst i m a gi n a bl e p ai n.  
 
 
•  
P ai n m e dic ati o ns  c h a n g es 
•  
A Es/ d evic e d efici e nci es  
1 0. 1 8  
U n s c h e d ul e d Vi sit s  
U nsc h e d ul e d visits  m a y occ ur if pr o gr a m mi n g c h a n g es ar e r e q uir e d t o c orr ect pr o gr a m mi n g err ors, t o 
r e pr o gr a m f or p ai n o pti miz ati o n, or f or a n A E.  W h e n ev er f e asi bl e, s u bj ects s h o ul d h a v e t h eir d evic es 
i nt err o g at e d.   
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d d uri n g u nsc h e d ul e d visits:  
 
 
•  
R e as o n f or visit  
•  
If a p plic a bl e, coll ect d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o 
M e dtr o nic  
•  
Fl u or osc o py/x -r ay, if n ec ess ar y 
•  
P ai n m e dic ati o ns  c h a n g es 
•  
A Es/ d evic e d efici e nci es  
1 0. 1 9  
D e vi c e I nt err o g ati o n  
F or visits occ urri n g at t h e st u dy sit e, c oll ect d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y 
s e n d t o M e dtr o nic.  S o urc e f or t h e i nt err o g ati o n r e p orts s h o ul d b e k e pt at t h e st u dy sit e.  It is 
r ec o m m e n d e d t h at d at a ar e n ot cl e ar e d d uri n g a ny i nt err o g ati o n.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 4 9  of 1 1 7  
 
 
 
 
 
1 0. 2 0  
S y st e m M o difi c ati o n  
Syst e m m o dific ati o ns ( e. g. l e a d or d e vic e r e visi o n, r e pl ac e m e nt, or ex pl a nt) m ay occ ur i n t h e st u dy d u e 
t o i n eff ectiv e or l oss of t h er a py, A Es, d e vic e d efici e nci es, or s u bj ect c o nc er ns t h at ar e n ot c orr ect a bl e by 
pr o gr a m mi n g.  I n t h e ev e nt of a s yst e m m o dific ati o n, t h e visit sc h e d ul e f or t h e s u bj ect will r e m ai n 
u nc h a n g e d.  If t h e S C S d e vic e r e q uir es r e pl ac e m e n t, c o nt act a m e m b er of t h e M e dtr o nic st u dy t e a m as 
t h e d ecisi o n t o all o w r e-i m pl a nt will b e h a n dl e d o n a c as e-by -c as e b asis.  If t h e s yst e m is ex pl a nt e d, t h e 
ex pl a nt e d syst e m will b e r et ur n e d t o M e dtr o nic.   All ex pl a nt e d pr o d uct s s h o ul d b e r et ur n e d t o 
M e dt r o nic f or a n alysis w h e n p er missi bl e by l oc al l a ws a n d r e g ul ati o ns. S e e S ecti o ns  7. 1 0  a n d 7. 1 1  f or 
fi n al pr o d uct dis p ositi o n d et ails. 
T h e f oll o wi n g i nf or m ati o n is r e q uir e d t o b e c oll ect e d d uri n g s yst e m m o dific ati o n visits: 
•  
C h a n g es t o t h e i m pl a nt e d syst e m  
•  
C oll ect d at a fil es vi a t h e cli nici a n pr o gr a m m er t a bl et a n d s ec ur el y s e n d t o M e dtr o nic  
•  
Fl u or osc o py/x -r ay, if n ec ess ar y 
•  
P ai n m e dic ati o ns  
•  
A Es/ d evic e d efici e nci es  
1 0. 2 1  
A s s e s s m e nt of Effi c a c y  
1 0. 2 1. 1  
O v er sti m ul ati o n S e n s ati o n  
All ass ess m e nts will b e d oc u m e nt e d i n a p a p er f or m at by t h e s u bj ect a n d tr a nsf err e d t o t h e a p pr o pri at e 
visit e C R F by a ut h oriz e d sit e p ers o n n el.  F or ev ery o v ersti m ul ati o n s e ns ati o n br o u g ht a b o ut by pr ot oc ol -
pr escri b e d acti viti es, s u bj ects will r at e t h e i nt e nsity of t h e s e ns ati o n i n t h e f oll o wi n g 5 -p oi nt Li k ert sc al e:  
•  
N o ov ersti m ul ati o n s e ns ati o n (c o d e = 0)  
•  
W e a k ov ersti m ul ati o n s e ns ati o n (c o d e = 1)  
•  
M o d er at e ov ersti m ul ati o n s e ns ati o n (c o d e = 2)  
•  
Str o n g ov ersti m ul ati o n s e ns ati o n (c o d e = 3)  
•  
V er y str o n g ov ersti m ul ati o n s e ns ati o n (c o d e = 4)  
 
 
 
 
1 0. 2 1. 3  
Vi s u al A n al o g u e S c al e  
P ai n will b e ass ess e d by V AS ( 0 – 1 0 0 m m).   T h e V A S sc al e r a n g es fr o m 0 m m m e a ni n g “ n o ov er all p ai n” 
a n d 1 0 0 m m m e a ni n g “ w orst ov er all  p ai n i m a gi n a bl e.”  S u bj ects will b e as k e d t o r e p ort p ai n i nt e nsity “i n 
t h e l ast 7 2  h o urs” by m ar ki n g a li n e p er p e n dic ul ar t o t h e V A S li n e at t h e p oi nt t h at r e pr es e nts t h eir p ai n 
i nt e nsit y.  Sit e p ers o n n el will d et er mi n e t h e sc or e by m e as uri n g t h e dist a nc e ( m m) o n t h e 1 0 0-m m li n e 
b et w e e n t h e l eft, “ n o p ai n” a nc h or a n d t h e s u bj ect’s m ar k, m e as uri n g t h e t ot al dist a nc e of t h e li n e (t o 
e ns ur e t h at it is 1 0 0 m m) , a n d di vi di n g t h e dist a nc e fr o m t h e “ n o p ai n” m ar k t o t h e s u bj ect’s m ar k by 
t h e t ot al dist a nc e of t h e li n e. T h e sc or e d V A S r a n g es fr o m 0 – 1 0 0.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 0  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
 
  
 
 
  
 
   
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 1  of 1 1 7  
 
 
 
 
 
 
 
 
 
  
 
  
 
 
 
 
 
 
 
  
 
   
 
 
 
    
 
 
 
 
 
   
1 0. 2 2  
A s s e s s m e nt of S af et y  
T o c h ar act eriz e all d evic e -r el at e d, t h er a py-r el at e d, a n d pr oc e d ur e-r el at e d a dv ers e ev e nts a n d d e vic e 
d efici e nci es.   A dv ers e e v e nts a n d d evic e d efici e nci es will b e s u m m ariz e d usi n g s u m m ary t a bl es 
dis pl a yi n g t h e fr e q u e nc y a n d p erc e nt a g es, by st u dy p h as e, a n d i n t ot al. A dv ers e e v e nts will b e 
s u m m ariz e d by s eri o us n ess as w ell. 
S e e S ecti o n 1 2  f or f urt h er i nf or m ati o n o n t h e c oll ecti o n of A Es a n d s af et y i nf or m ati o n. 
1 0. 2 3  
R e c or di n g D at a  
D at a e nt er e d m ust b e tr ac e a bl e t o s o urc e d oc u m e nts. S o urc e d oc u m e nt ati o n is d efi n e d as t h e first ti m e 
d at a a p p e ar, a n d m ay i ncl u d e ori gi n al d oc u m e nts, d at a, a n d r ec or ds ( e. g., h os pit al r ec or ds, cli nic al a n d 
offic e c h arts, pr oc e d ur e r e p orts, l a b or at ory n ot es, m e m or a n d a, s u bj ects’ di ari es or ev al u ati o n 
c h ec klists, p h ar m ac y dis p e nsi n g r ec or ds, r ec or d e d d at a fr o m a ut o m at e d i nstr u m e nts, c o pi es or 
tr a nscri pti o ns c ertifi e d aft er v erific atio n as b ei n g acc ur at e c o pi es, micr ofic h es, p h ot o gr a p hic n e g ativ es, 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 2  of 1 1 7  
 
 
 
 
 
micr ofil m or m a g n etic m e di a, X -r a ys, s u bj ect fil es, d evic e d at a a n d r ec or ds k e pt at t h e p h ar m ac y, at t h e 
l a b or at ori es a n d at m e dic o-t ec h nic al d e p art m e nts i nv ol v e d i n t h e st u dy). 
I nt err o g ati on fil es will b e c oll ect e d a n d st or e d at t h e sit e. Ps e u d o ny miz e d c o pi es of t h e i nt err o g ati o n 
fil es s u b mitt e d t o M e dtr o nic s h o ul d b e s e nt vi a s ec ur e a n d c o m pli a nt el ectr o nic fil e tr a nsf er s ervic es 
a n d/ or s ec ur e m ail.  
Fl u or osc o py or x-r ay i m a g es s h all b e c oll ect e d a n d st or e d o n a C D/ D V D or U S B fl as h dri v e at 
t h e sit e. Ps e u d o ny miz e d c o pi es of t h os e i m a g es s u b mitt e d t o M e dtr o nic s h all b e s e nt vi a s ec ur e a n d 
c o m pli a nt el ectr o nic fil e tr a nsf er s ervic es a n d/ or s ec ur e m ail.  
I n g e n er al, e C R Fs ( or p a p er c o pi es) m a y n ot s erv e as s o urc e d oc u m e nts. A n exc e pti o n m a y b e t h e 
c o m pl eti o n of q u esti o n n air es a n d cli nic al sc al es. S o urc e d oc u m e nt ati o n f or d at a el e m e nts n ot r o uti n ely 
c a pt ur e d i n m e dic al r ec or ds m ay v ar y fr o m st u dy sit e t o st u dy sit e; t h e st u dy s it e m ay us e s o urc e 
d oc u m e nt w orks h e ets if i d e ntifi e d as s o urc e d oc u m e nts.  
T h e Inv esti g at or m ust e ns ur e t h e a v ail a bility of s o urc e d oc u m e nts fr o m w hic h t h e i nf or m ati o n o n t h e 
e C R Fs w as d eriv e d. T h e ty p e a n d l oc ati o n of s o urc e d oc u m e nts s h o ul d b e d oc u m e nt e d.  W h er e pri nt o uts 
of el ectr o nic m e dic al r ec or ds, ar e pr o vi d e d as s o urc e d oc u m e nts, or w h er e c o pi es of s o urc e d oc u m e nts 
ar e r et ai n e d as s o urc e d oc u m e nts, t h os e s h o ul d b e c ertifi e d. C ertific ati o n m ust c o nt ai n ( 1) t h e si g n at ur e 
of t h e i n divi d u al m a ki n g t h e c o p y, ( 2) t h e d at e t h e c o py w as m a d e.  
T h e s o urc e d oc u m e nts m ust b e m a d e a v ail a bl e f or m o nit ori n g or a u diti n g by M e dtr o nic’s r e pr es e nt ativ e 
or r e pr es e nt ati v es of t h e c o m p et e nt a ut h oriti es a n d ot h er a p plic a bl e r e g ul at ory a g e nci es.  
T h e C R F m ay b e c o nsi d er e d s o u rc e f or t h e f oll o wi n g d at a c oll ecti o n el e m e nts: 
•  
E nr oll m e nt N otific ati o n  
 
St u dy sit e assi g n e d s u bj ect r ef er e nc e  
•  
B as eli n e  
 
A d mi nistr ativ e i nf or m ati o n  
•  
A E e C R F  
 
D at e st u dy sit e b ec a m e a w ar e of ev e nt  
 
R el at e d n ess of a dv ers e ev e nt  
•  
D evic e D efici e ncy  e C R F  
 
D at e st u dy sit e b ec a m e a w ar e of ev e nt 
•  
S u bj ect D e at h  
 
D at e st u dy sit e b ec a m e a w ar e of d e at h  
 
R el at e d n ess of d e at h  
 
Syst e m ex pl a nt i nf or m ati o n  
•  
D evi ati o ns  
 
R e as o n f or d e vi ati o n  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 3  of 1 1 7  
 
 
 
 
 
1 0. 2 4  
D e vi ati o n H a n dli n g  
A st u dy d evi ati o n is d efi n e d as a n ev e nt wit hi n a st u dy t h at di d n ot occ ur acc or di n g t o t h e CI P or t h e 
C T A.  
Pri or a p pr ov al by M e dtr o nic is ex p ect e d i n sit u ati o ns w h er e t h e i nv esti g at or a ntici p at es, c o nt e m pl at es, 
or m a k es a c o nsci o us d ecisi o n t o d evi at e. Pri or a p pr o v al is n ot r e q uir e d w h e n a d e vi ati o n is n ec ess ar y t o 
pr ot ect  t h e s af et y, ri g hts or w ell-b ei n g of a s u bj ect i n a n e m er g e ncy or i n u nf or es e e n sit u ati o ns b e y o n d 
t h e i nv esti g at or’s c o ntr ol ( e. g. s u bj ect f ail ur e t o att e n d sc h e d ul e d visits, i n a dv ert e nt l oss of d at a d u e t o 
c o m p ut er m alf u ncti o n, i n a bilit y t o p erf or m r e q uire d pr oc e d ur es d u e t o s u bj ect ill n ess).  
F or m e dic ally j ustifi a bl e c o n diti o ns w hic h pr e e m pt a s u bj ect’s a bility t o c o m pl et e a st u dy -r e q uir e d 
pr oc e d ur e, it m ay b e p er mitt e d t o r e p ort o nly o n e d evi ati o n w hic h will a p ply t o all visits g oi n g f or w ar d. 
T his m ay al s o a p ply f or ot h er u nf or es e e n sit u ati o ns ( e. g. t h e s u bj ect p er m a n e ntly r ef us es t o c o m pl et e a 
st u dy r e q uir e d pr oc e d ur e a n d t h e d at a will n ot c o ntri b ut e t o t h e pri m ar y e n d p oi nt a n al ysis). H o w e v er, 
pri or a p pr ov al fr o m M e dtr o nic is r e q uir e d f or s uc h sit u ati o n s.  
All st u dy d evi ati o ns m ust b e r e p ort e d o n t h e C R F r e g ar dl ess of w h et h er m e dic all y j ustifi a bl e, pr e -
a p pr o v e d by M e dtr o nic, a n i n a dv ert e nt occ urr e nc e, or t a k e n t o pr ot ect t h e s u bj ect i n a n e m er g e nc y. 
M ulti pl e d evi ati o ns of t h e s a m e t y p e at t h e s a m e visit m a y b e r e p ort e d o n o n e c as e r e p ort f or m.  
I n t h e ev e nt t h e d e vi ati o n i nv olv es a f ail ur e t o o bt ai n a s u bj ect’s c o ns e nt, or is m a d e t o pr ot ect t h e lif e 
or p hysic al w ell -b ei n g of a s u bj ect i n a n e m er g e ncy, t h e d e vi ati o n m ust b e r e p ort e d t o t h e E C as w ell as 
M e dtr o nic wit hi n fi v e ( 5) w or ki n g d a ys.  R e p orti n g of all ot h er st u dy d e vi ati o ns s h o ul d c o m ply wit h E C 
p olici es a n d/ or l oc al l a ws a n d m ust b e r e p ort e d t o M e dtr o nic as s o o n as p ossi bl e u p o n t h e st u dy sit e 
b ec o mi n g a w ar e of t h e d evi ati o n. R e p orti n g of d evi ati o ns m ust c o m pl y wit h E C p olici es, l oc al l a ws, 
a n d/ or R e g ul at or y A ut h ority  r e q uir e m e nts. R ef er t o I nv esti g at or R e p orts, T a bl e 8  f or d evi ati o n r e p orti n g 
r e q uir e m e nts a n d ti m efr a m es f or r e p orti n g t o M e dtr o nic a n d/ or R e g ul at or y A ut h orit y .  
M e dtr o nic is r es p o nsi bl e f or a n al yzi n g d e vi ati o ns, ass essi n g t h eir si g nific a nc e, a n d i d e ntif yi n g a ny 
a d diti o n al c orr ecti v e a n d/ or pr e v e nti v e acti o ns ( e. g. a m e n d t h e CI P, c o n d uct a d diti o n al tr ai ni n g, 
t er mi n at e t h e i nv esti g ati o n). R e p etiti v e or s eri o us i nv esti g at or c o m pli a nc e iss u es m a y r es ult i n i niti ati o n 
of a c orr ectiv e acti o n pl a n wit h t h e i nv esti g at or a n d st u dy sit e, a n d i n s o m e c as es, m ay n ec essit at e 
s us p e n di n g e nr oll m e nt u ntil t h e pr o ble m is r es olv e d or ulti m at el y t er mi n ati n g t h e i nv esti g at or's 
p artici p ati o n i n t h e st u dy. M e dtr o nic will pr ovi d e st u dy sit e -s p ecific r e p orts t o i nv esti g at ors s u m m arizi n g 
i nf or m ati o n o n d evi ati o ns t h at occ urr e d at t h e i nv esti g ati o n al st u dy sit e o n a p eri o dic b asis.  
Ex a m pl es of st u dy d evi ati o ns i ncl u d e b ut ar e n ot li mit e d t o:  
•  
F ail ur e t o o bt ai n pr o p er I C  
•  
F ail ur e t o c oll ect r e q uir e d st u dy d at a  
•  
I ncl usi o n/ excl usi o n crit eri a n ot m et 
•  
Missi n g r e q uir e d d e vic e i nt err o g ati o n fil es  
•  
Visits o ut of wi n d o w  
1 0. 2 5  
S u bj e ct E xit, Wit h dr a w al or Di s c o nti n u ati o n  
1 0. 2 5. 1  
St u d y E xit  
A st u dy exit e C R F is r e q uir e d f or all s u bj ects. Pri or t o exiti n g a s u bj ect fr o m t h e st u dy, it is r ec o m m e n d e d 
t o f oll o w t h e s u bj ect u ntil all o n g oi n g syst e m a n d/ or pr oc e d ur e r el at e d A Es ar e r es ol v e d or u nr es ol v e d 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 4  of 1 1 7  
 
 
 
 
 
wit h n o f urt h er acti o ns pl a n n e d , or u ntil offici al st u dy cl os ur e, w hic h ev er occ urs first.  F oll o wi n g exit, 
s u bj ects will c o nti n u e t o r ec ei v e st a n d ar d m e dic al c ar e as t h e y w o ul d h a vi n g r ec ei v e d a c o m m erci all y 
av ail a bl e S C S d e vic e  a n d b e f oll o w e d p er I nv esti g at or discr eti o n . U p o n exiti n g fr o m t h e st u dy, n o f urt h er 
st u dy d at a will b e c oll ect e d or st u dy visits will occ ur f or t h e s u bj ect.  All d at a av ail a bl e t hr o u g h t h e ti m e 
of t h e s u bj ect’s exit will b e us e d f or a n al ysis.  
S u bj ects ar e ur g e d t o r e m ai n i n t h e st u dy as l o n g as p ossi bl e b ut m ay b e exit e d fr o m t h e st u dy f or a ny of 
t h e f oll o wi n g sit u ati o ns: 
•  
St u dy c o m pl et e d  
•  
S u bj ect l ost t o f oll o w -u p  
•  
S u bj ect d e at h  
•  
S u bj ect di d n ot m e et i ncl usi o n/ excl usi o n crit eri a  
•  
S u bj ect w as n ot i m pl a nt e d wit h t h e st u dy  d e vic e  
•  
S u bj e ct di d n ot pr ovi d e i nf or m e d c o ns e nt  
•  
S u bj ect c h o os es t o wit h dr a w ( e. g., c o ns e nt wit h dr a w al, r el oc ati o n t o a n ot h er 
g e o gr a p hic l oc ati o n)  
•  
I nv esti g at or d e e ms wit h dr a w al n ec ess ary ( e. g., m e dic all y j ustifi e d, i ncl usi o n/ excl usi o n 
crit eri a n ot m et, f ail ur e of s u bj ect t o m ai nt ai n a d e q u at e st u dy c o m pli a nc e)  
C o m pl et e a n U nsc h e d ul e d V isit if t h e s u bj ect exits e arly, b et w e e n visits a n d pri or t o t h e last st u dy visit : 
1 0. 2 5. 2  
St u d y C o m pl et e d  
At t h e c o m pl eti o n of t h e 2 4 - Mo nt h  Visit, s u bj ects will b e exit e d fr o m t h e st u dy. T h e 2 4 - Mo nt h  Visit a n d 
exit visit s h o ul d b e c o m bi n e d, a n d b ot h a 2 4 - Mo nt h Visit  C R F a n d a St u dy Exit C RF n e e d t o b e 
c o m pl et e d.  
1 0. 2 5. 3  
L o st t o F oll o w - u p 
A s u bj ect is c o nsi d er e d t o b e l ost t o f oll o w -u p if at l e ast t w o att e m pts t o c o nt act t h e s u bj ect ar e 
u ns ucc essf ul. T h e m et h o d of att e m pt ( e. g., o n e l ett er a n d o n e p h o n e r ec or d, or t w o l ett ers) m ust b e 
d oc u m e nt e d i n t h e s u bj ect’s m e dic al r ec or d. I n a d diti o n, r e g ul ati o n s et f ort h by t h e g ov er ni n g E C m ust 
b e f oll o w e d.  
1 1.  Ri s k s a n d B e n efit s  
1 1. 1  P ot e nti al Ri s k s  
M e dtr o nic f oll o ws ri g or o us Q u alit y Ass ur a nc e a n d C o ntr ol pr oc e d ur es t hr o u g h o ut t h e lif e of a pr o d uct, 
fr o m t h e b usi n ess a n alysis p h as e t hr o u g h d ev el o p m e nt, m ark et r el e as e, a n d p ost-m ar k et s ur v eill a nc e. 
T h e ris k a n al ysis pr oc ess f or t h e I nc e pti v s yst e m is b ei n g p erf or m e d i n acc or d a nc e wit h I S O 1 4 9 7 1, a n d 
will e ns ur e t h at t h e l ev el of ris k is as l o w as p ossi bl e pri or t o st arti n g t h e st u dy.  
It is a ntici p at e d t h er e ar e n o i ncr e m e nt al ris ks i ntr o d uc e d t o t h e s u bj ect as a r es ult of p artici p ati o n i n 
t his st u dy or wit h t h e i m pl a nt ati o n of t h e I nc e ptiv syst e m.  A ny n e w i d e ntifi e d risks will b e 
c o m m u nic at e d t o I nv esti g at ors a n d r es ult i n a CI P r evisi o n.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 5  of 1 1 7  
 
 
 
 
 
1 1. 2  F or e s e e a bl e Ri s k s  
1 1. 2. 1  
S C S A d v er s e E v e nt s S u m m ar y  
T h e i m pl a nt ati o n of a S C S syst e m i nv olv es ris ks t h at ar e si mil ar t o ot h er s pi n al c or d pr oc e d ur es.  I n 
a d diti o n t o t h os e ris ks ass oci at e d wit h s ur g ery, t h e f oll o wi n g a dv ers e ev e nts m a y occ ur wit h 
i m pl a nt ati o n or us es of a n e ur osti m ul ati o n syst e m. 
•  
All er gic or i m m u n e s yst e m r es p o ns e t o t h e i m pl a nt e d m at eri als  
•  
I nf ecti o n 
•  
L e a d, ext e nsi o n, or n e ur osti m ul at or er osi o n t hr o u g h t h e s ki n or mi gr ati o n  
•  
L e a k a g e of c er e br os pi n al fl ui d 
•  
L oss of p ai n r eli ef m a y r et ur n p ati e nts t o t h eir u n d erlyi n g p ai n c o n diti o n  
•  
P ati e nts o n a ntic o a g ul ati o n t h er a pi es m a y b e at gr e at er ris k f or p ost o p er ati v e c o m plic ati o ns s uc h 
as h e m at o m as t h at c a n r es ult i n p ar al ysis  
•  
P ersist e nt p ai n at t h e n e ur osti m ul at or sit e  
•  
Pl ac e m e nt of t h e e pi d ur al l e a d -ext e nsi o n is a s ur gic al pr oc e d ur e t h at m a y ex p os e p ati e nts t o risks 
of e pi d ur al h e m orr h a g e, h e m at o m a, or p ar alysis  
•  
R a dic ul a r c h est w all sti m ul ati o n 
•  
S er o m a or h e m at o m a at t h e n e ur osti m ul at or sit e  
•  
C h a n g e i n sti m ul ati o n, p ossi bl y r el at e d t o c ell ul ar c h a n g es ar o u n d t h e el ectr o d e(s), s hifts i n 
el ectr o d e p ositi o n, l o os e el ectric al c o n n ecti o ns, l e a d or ext e nsi o n fr act ur es, w hic h h as b e e n 
d escri b e d by s o m e p ati e nts as u nc o mf ort a bl e sti m ul ati o n (j olti n g or s h oc ki n g s e ns ati o n).  
•  
F or m ati o n of r e acti v e tiss u e ar o u n d t h e l e a d i n t h e e pi d ur al s p ac e c a n r es ult i n d el a y e d s pi n al 
c or d c o m pr essi o n a n d p ar al ysis, r e q uiri n g s ur gic al i nt er v e nti o n. T i m e t o o ns et c a n r a n g e fr o m 
w e eks t o m a ny y e ars aft er i m pl a nt.  
•  
Sti m ul ati o n -d e p e n d e nt g astr oi nt esti n al s y m pt o ms s uc h as n a us e a, di arr h e a, i nc o nti n e nc e, or 
c o nsti p ati o n 
•  
Sti m ul ati o n -d e p e n d e nt bl a d d er s y m pt o ms s uc h as uri n ar y r et e nti o n, i nc o nti n e nc e, or fr e q u e ncy  
•  
Tiss u e d a m a g e at t h e i m pl a nt sit e  
1 1. 2. 2  
D e vi c e / S oft w ar e D efi ci e n ci e s Ri s k s  
T h e us e of S C S s yst e ms i ncl u d e ris k of t h e f oll o wi n g d evic e d efici e nci es:  
•  
M ec h a nic al f ail ur e/ d a m a g es of s yst e m c o m p o n e nts, e. g., l e a d fr act ur e (i ncr e as e d i m p e d a nc e), 
or br e ac h of i ns ul ati o n  
•  
Mi gr ati o n or disl o d g e m e nt of t h e l e a d(s)  
•  
Pr o gr a m mi n g a n d/ or t el e m etr y pr o bl e ms t h at mi g ht li mit t h e c a p a bility t o pr o gr a m or 
d et er mi n e w h at p ar a m et ers ar e pr o gr a m m e d  
•  
A ut o m atic a dj ust m e nt of o ut p ut t h at mi g ht pr o vi d e o ut p ut t h at is b el o w or a b o v e t h e d esir e d 
v al u es 
•  
O utsi d e el ectr o m a g n etic i nt erf er e nc e ( e. g., c ar di o v ersi o n, d efi brill ati o n, el ectr oc a ut er y etc.) 
mi g ht aff ect t h at o ut p ut or pr o gr a m mi n g of t h e s yst e m  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 6  of 1 1 7  
 
 
 
 
 
1 1. 2. 3  
R a di o gr a p hi c Ri s k s  
As p art of t h e st u dy, s u bj ects m a y  b e r e q uir e d t o h a v e fl u or osc o pic or X -r a y i m a g es t a k e n of t h eir d e vic e 
a n d/ or  l e a ds t h at ar e a d diti o n al t o t h os e r e q uir e d f or c o m m erci al pr oc e d ur es .  T his r e pr es e nts a 
n e gli gi bl e a m o u nt of a d ditiv e r a di ati o n ex p os ur e b ey o n d i m a gi n g us e d as p art of a st a n d ar d tri al l e a d 
pl ac e m e nt.  Wi n ni n g er
4 1  f o u n d t h at t h e m e a n t ot al fl u or osc o py ti m e f or S C S tri ali n g pr oc e d ur es ( n = 1 1 0) 
av er a g e d 1 3 3. 4 s wit h a st a n d ar d d e vi ati o n of 8 4. 8 s , wit h a d diti o n al i m a gi n g r e q uir e d f or i m pl a nt of 
p er m a n e nt l e a ds a n d t h e I N S .  F or  ex a m pl e, fiv e i m a g es ar e r o u g hl y t h e e q ui v al e nt of 1. 7 s of p uls e d 
fl u or osc o py at t h e l o w est fr a m e r at e ( 3 p uls es/s). T his is m uc h l o w er t h a n t h e a v er a g e ti m e f or t h e 
tri ali n g pr oc e d ur e ( at t h e m ost c o ns erv ativ e esti m at e of 3 p uls es/s) a n d u n d er o n e -t e nt h of a st a n d ar d 
d e vi ati o n fr o m t h e m e a n. F urt h er, Sc h mi d 4 2 f o u n d t h at 1 mi n. of p uls e d fl u or osc o py at 3 p uls es/s ( 1 8 0 
i m a g es— f ar a b ov e w h a t is a ntici p at e d f or t his st u dy  b e y o n d c o m m erci al pr oc e d ur es) f or fl u o r osc o py-
g ui d e d p eri n e ur al/ e pi d ur al i nj ecti o ns of t h e l u m b ar s pi n e ( a r e as o n a bl e a n al o g t o t h e t h or acic i m a gi n g 
p erf or m e d as p art of t his st u dy) r es ults i n a n eff ectiv e d os e of 0. 0 7 m Sv a n d 0. 0 8 m Sv i n m al es a n d 
f e m al es, r es p ectiv ely. Pr a d h a n4 3 r e p orts t h at c a ncer ris k c a n’t b e esti m at e d fr o m d os es b el o w 1 0 0 m Sv.  
1 1. 3  Ri s k Mi ni mi z ati o n  
T h e p ot e nti al ris ks ass oci at e d wit h I nc e pti v s yst e m w er e i d e ntifi e d a n d ris k c o ntr ol m e as ur es w er e 
d efi n e d .  A ny p ot e nti al ris ks ass oci at e d wit h t his st u dy ar e f urt h er mi ni miz e d by s el ecti n g q u alifi e d 
i nv esti g at ors a n d tr ai ni n g st u dy p ers o n n el o n t h e CI P.  
I n a d diti o n, Inv esti g at ors will b e activ ely i nv olv e d i n t h e i m pl a nt ati o n a n d f oll o w -u p of t h e s u bj ects 
i mpl a nt e d wit h t h e S C S  syst e ms.  
Ris ks will b e mi ni miz e d by c ar ef ul ass ess m e nt of e ac h s u bj ect pri or t o, d uri n g, a n d aft er i m pl a nt of t h e 
S C S .  Pri or t o i m pl a nt, it is r ec o m m e n d e d s u bj ects u n d er g o a c o m pl et e p hysic al ev al u ati o n.  
M e dtr o nic h as f urt h er mi ni miz e d t h e p ossi bilit y of risks by p erf or mi n g r e q uir e d l a b or at or y a n d pr e -
cli nic al t esti n g pri or t o t h e Cl os e d -L o o p S C S st u dy, i m pl e m e nti n g q u ality c o ntr ol m e as ur es i nt o 
pr o d ucti o n pr oc ess es, pr ovi di n g g ui d eli n es f or s u bj ect s el ecti o n a n d e v al u ati o n, a n d pr o vi di n g a d e q u at e 
i nstr ucti o ns a n d l a b eli n g.  
Aft er i m pl a nt ati o n, s u bj ects i n t h e Cl os e d -L o o p S C S st u dy will b e f oll o w e d at r e g ul ar i nt er v als t o m o nit or 
t h e c o n diti o n of t h e i m pl a nt e d s yst e m a n d t h e b att ery.  At e ac h r e q uir e d visit , t h e Inv esti g at or m ust 
i nt err o g at e t h e S C S  t o v erify a p pr o pri at e f u ncti o n a n d t o e v al u at e p aci n g a n d s e nsi n g c h ar act eristics a n d 
t o ass ess a ny a dv ers e ev e nts.  I nf or m e d c o ns e nt will i ncl u d e d escri pti o n f or t h e s u bj ect t o u n d erst a n d 
t h at t h e s u bj ect s h o ul d i nf or m a ny h e alt h c ar e p ers o n n el b ef or e a ny m e dic al pr oc e d ur e, t h at t h ey h a v e 
a n i m pl a nt e d S C S s yst e m.  A d diti o n all y, if t h e s u bj ect will u n d er g o a c ar di o v ersi o n  or d efi brill ati o n , wit h 
th e i m pl a nt e d S C S syst e m, e ns ur e t h at sti m ul ati o n is t ur n e d off f or t h e d ur ati o n of t h e m e dic al 
pr oc e d ur e.  Pl e as e r ef er t o t h e I nv esti g at or’s Br oc h ur e, I nf or m ati o n f or Pr escri b ers or t h e P ati e nt 
T h er a py G ui d e f or a d diti o n al i nf or m ati o n.  
1 1. 4  P ot e nti al B e n efit s  
T h e I nc e ptiv syst e m m a y off er n o b e n efit. T h e p ot e nti al b e n efi t of h avi n g t h e I nc e pti v syst e m, a b o v e a n d 
b e y o n d S C S t h er a py  f or t h e tr e at m e nt of c hr o nic p ai n, is t h e r e d ucti o n of ov ersti m ul ati o n ev e nts, if t h e 
cl os e d-l o o p f e at ur e is e n a bl e d.  T h e i nf or m ati o n g ai n e d fr o m t his st u dy c o ul d r es ult i n t h e i m pr ov e d 
m a n a g e m e nt of ot h er p ati e nts wit h c hr o nic p ai n .  A d diti o n all y, i nf or m ati o n c oll ect e d fr o m t his st u dy 
m a y assist i n t h e d esi g n of n e w pr o d uct(s)/t h er a py(i es).  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 7  of 1 1 7  
 
 
 
 
 
1 1. 5  Ri s k -B e n efit R ati o n al e  
T h e b e n efit of t h e st u dy li es i n t h e k n o wl e d g e t o b e g ai n e d fr o m t h e r es ults a n d t h e p ot e nti al t o i m pr o v e 
S C S t h er a py.  All p ot e nti al ris ks h a v e b e e n c o ntr oll e d t o a l e v el as f ar as p ossi bl e.  A n y r esi d u al risk is 
d et er mi n e d t o b e acc e pt a bl e gi v e n t h e ex p ect e d b e n efit.  
1 2.  A d v er s e E v e nt s a n d D e vi c e D efi ci e n ci e s  
1 2. 1  A d v er s e E v e nt s  
A E d efi niti o ns ar e pr ovi d e d i n T a bl e 7 . T h e f oll o wi n g A Es will b e c oll ect e d t hr o u g h o ut t h e st u dy d ur ati o n, 
st arti n g at t h e ti m e of si g ni n g t h e I C: 
•  
pr oc e d ur e r el at e d  
•  
d e v ic e r el at e d 
•  
t h er a py r el at e d 
•  
s eri o us a dv ers e e v e nts r e g ar dl ess of r el at e d n ess 
R e p orti n g of t h es e ev e nts t o M e dtr o nic will occ ur o n a n A E e C R F .  E ac h e v e nt m ust b e r e p ort e d 
s e p ar at ely.  D oc u m e nt e d pr e -existi n g c o n diti o ns ar e n ot c o nsi d er e d A Es u nl ess t h e n at ur e or s ev erity of 
t h e c o n diti o n h as w ors e n e d.  A s u bs et of A Es will b e c oll ect e d i n t his st u dy  as t h es e ar e t h e m ost 
r el e v a nt t o t h e st u dy d evic e a n d st u dy d esi g n gi v e n n o n e w or i ncr e as e d risk wit h t h e I nc e ptiv syst e m. 
U A E, list e d i n T a bl e 7 , n e e d n ot b e r e p ort e d u nl ess t h e a dv ers e ev e nt w ors e ns or is pr es e nt o utsi d e t h e 
st at e d ti m efr a m e p ost-i m pl a nt.  
F or A Es t h at r e q uir e i m m e di at e r e p orti n g (s e e T a bl e 9 ), i niti al r e p orti n g m a y b e d o n e by p h o n e, f ax, or 
o n t h e e C R F c o m pl eti n g as m uc h i nf or m ati o n as p ossi bl e.  T h e c o m pl et e d A E C R F m ust b e s u b mitt e d t o 
M e dtr o nic as s o o n as p ossi bl e.   
A ny m e dic ati o n/tr e at m e nt ass oci at e d wit h t h e tr e at m e nt of a n A E m ust b e r e p ort e d  
S u bj ect d e at hs ar e als o r e q uir e d t o b e r e p ort e d.  R ef er t o S ecti o n 1 2. 6  f or S u bj ect D e at h c oll ecti o n a n d 
r e p orti n g r e q uir e m e nts. 
E v e nts t h at ar e n ot  r e p ort a bl e f or t his st u dy ar e: 
•  
S e ns ati o n of sti m ul ati o n ( p ar est h esi a)  
o  S e ns ati o n of sti m ul ati o n ( e. g. , ti n gli n g, b uzzi n g) will n ot b e r e p ort e d as t his m a y occ ur as 
p art of t his t h er a py.  
o  S e ns ati o n of sti m ul ati o n br o u g ht by pr ot oc ol -pr escri b e d activiti es (i. e . c o u g hi n g, 
l a u g hi n g, V als al v a) if tr a nsi e nt a n d r ev ers e d by t h e s u bj ect r et ur ni n g t o a n e utr al 
p ositi o n  ( a nyti m e occ urr e d).  
o  O v ersti m ul ati o n : u nc o mf ort a bl e  s e ns ati o n of sti m ul ati o n (i nt e ns e ti n gli n g, s h oc ki n g, 
j olti n g) br o u g ht by pr ot oc ol-pr escri b e d activiti es  if tr a nsi e nt a n d r ev ers e d by t h e s u bj ect 
r et ur ni n g t o a n e utr al p ositi o n ( as d efi n e d i n S ecti o n 1 4. 4 ). 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 8  of 1 1 7  
 
 
 
 
 
•  
Tr a nsi e nt p eri o ds of s e ns ati o n or sti m ul ati o n ev e nts t h at ar e u nc o mf ort a bl e t o t h e s u bj ect t h at 
d o n ot r es ult  i n a n i nt er v e nti o n or ar e r eli e v e d by c h a n g e i n b o dy p ositi o n or d ecr e asi n g t h er a py 
i nt e nsit y 
N O T E:  E xt e n d e d p eri o ds of s e ns ati o n or o v ersti m ul ati o n e v e nts t h at ar e u nc o mf ort a bl e t o t h e s u bj ect 
( e. g. ti n gli n g, s h oc ki n g, j olti n g) t h at r es ult i n i nt er v e nti on ( e. g. r e pr o gr a m mi n g, t ur ni n g t h e d e vic e off) 
will b e r e p ort e d.  
1 2. 2  D e vi c e D efi ci e n c y  
T h e d evic e d efici e ncy  d efi niti o n is pr o vi d e d i n T a bl e 7 .  D e vic e d efici e nc y i nf or m atio n will b e c oll ect e d 
t hr o u g h o ut t h e st u dy a n d r e p ort e d t o M e dtr o nic.  N ot e t h at d e vic e d efici e nc y t h at r es ult i n a n A E t o t h e 
s u bj ect s h o ul d b e c a pt ur e d as a n A E o nl y.  D e vic e d efici e nci es  t h at l e d t o i ncr e asi n g p ai n, b ut still b el o w 
b as eli n e p ai n  l ev els s h o ul d b e r e p ort e d as o nly  a d e vic e d efici e nc y , n ot a n A E. 
D evic e d efici e ncy t h at di d n ot l e a d t o a n A E b ut c o ul d h a v e l e d t o a S A D E (i. e., if s uit a bl e acti o n h a d n ot 
b e e n t a k e n, if i nt er v e nti o n h a d n ot b e e n m a d e, or if t h e circ u mst a nc es h a d b e e n l ess f ort u n at e) r e q uir e 
i m m e di at e r e p orti ng (s e e T a bl e 9). 
1 2. 3  Pr o c e s si n g U p d at e s a n d R e s ol uti o n  
F or a ny c h a n g es i n st at us of a pr evi o usly r e p ort e d a dv ers e e v e nt or d evic e d efici e nc y  (i. e. c h a n g e i n 
acti o ns t a k e n, c h a n g e i n o utc o m e, c h a n g e i n r el at e d n ess), i nf or m ati o n n e e ds t o b e u p d at e d o n, or 
a d d e d t o t h e ori gi n al A E or d e vic e d efici e nc y f or m.  All A Es m ust b e f oll o w e d u ntil t h e A E h as b e e n 
r es olv e d, is u nr es ol v e d wit h n o f urt h er acti o ns pl a n n e d, t h e s u bj ect di es or exits t h e st u dy, or u ntil st u dy 
cl os ur e, w hic h ev er occ urs first.  
I n t h e ev e nt t h at a s u bj ect is exit e d fr o m t h e st u dy pri or t o st u dy c o m pl eti o n, all eff orts s h o ul d b e m a d e 
t o c o nti n u e f oll o wi n g t h e s u bj ect u ntil all o n g oi n g  d e vic e  a n d/ or pr oc e d ur e r el at e d A Es, as cl assifi e d by 
t h e i nv esti g at or, ar e r es olv e d, u nr es ol v e d wit h n o f urt h er acti o ns pl a n n e d, or u ntil offici al st u dy cl os ur e , 
w hic h e v er occ urs first .  At t h e ti m e of st u dy exit, all c oll ect e d A Es  wit h a n o utc o m e of “ n ot 
r ec ov er e d/ n ot r es olv e d”, “r ec ov eri n g/r es ol vi n g” or “ u n k n o w n” m ust b e r evi e w e d a n d u p d at es pr ovi d e d 
as a p plic a bl e . 
1 2. 4  D efi niti o n s / Cl a s sifi c ati o n s  
F or t h e p ur p os es of t h e cli nic al r e p ort, M e dtr o nic will cl assif y e ac h a dv ers e ev e nt acc or di n g t o  I S O 
1 4 1 5 5: 2 0 2 0 .  W h er e t h e d efi niti o n i n dic at es “ d e vic e”, it r ef ers t o a ny d evic e us e d i n t h e st u dy.  T his 
mi g ht b e t h e d evic e u n d er i nv esti g ati o n, or a ny m ar k et r el e as e d c o m p o n e nt of t h e s yst e m .  It is th e 
r es p o nsi bility of t h e I nv esti g at or t o i d e ntif y t h e occ urr e nc e of all A Es a n d d evic e d efici e nci es a n d t o 
e ns ur e t h e r e q uir e d i nf or m ati o n is acc ur at el y d oc u m e nt e d i n t h e m e dic al r ec or ds a n d r e p ort e d t o 
M e dtr o nic.  
T a bl e 7 : A d v er s e E v e nt a n d D e vi c e D efi ci e n c y D efi niti o n s 
G e n er al  
A dv ers e E v e nt  ( A E) 
U nt o w ar d m e dic al occ urr e nc e, u ni nt e n d e d dis e as e or i nj ur y, or 
u nt o w ar d cli nic al si g ns (i ncl u di n g a b n or m al l a b or at or y fi n di n gs) i n 
s u bj ects, us ers or ot h er p ers o ns, w h et h er or n ot r el at e d t o t h e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 5 9  of 1 1 7  
 
 
 
 
 
i nv esti g ati o n al m e dic al d evic e a n d w h et h er a ntici p at e d or 
u n a n tici p at e d.  
N ot e 1: T his d efi niti o n i ncl u d es e v e nts r el at e d t o t h e i nv esti g ati o n al 
m e dic al d e vic e or t h e c o m p ar at or.  
N ot e 2: T his d efi niti o n i ncl u d es e v e nts r el at e d t o t h e pr oc e d ur es 
i nv olv e d.  
N ot e 3: F or us ers or ot h er p ers o ns, t his d efi niti o n is r estri ct e d t o 
e v e nts r el at e d t o i nv esti g ati o n al m e dic al d e vic es.  
(I S O 1 4 1 5 5: 2 0 2 0, 3. 2)  
A dv ers e D e vic e Eff ect ( A D E)  
 
A E r el at e d t o t h e us e of a n i nv esti g ati o n al m e dic al d evic e.  
N ot e 1: T his d efi niti o n i ncl u d es A Es r es ulti n g fr o m i ns uffici e nt or 
i n a d e q u at e i nstr ucti o ns f or us e, d e pl o y m e nt, i m pl a nt ati o n, 
i nst all ati o n, or o p er ati o n, or a ny m alf u ncti o n of t h e i nv esti g ati o n al 
m e dic al d e vic e.  
N ot e 2: T his d efi niti o n i ncl u d es a ny e v e nt  r es ulti n g fr o m a n us e 
err or or fr o m i nt e nti o n al mis us e of t h e i nv esti g ati o n al m e dic al 
d e vic e.  
N ot e  3: t his i ncl u d es ‘c o m p ar at or’ if t h e c o m p ar at or is a m e dic al 
d e vic e  
(I S O 1 4 1 5 5: 2 0 2 0, 3. 1)  
D evic e D efici e ncy  
 
I n a d e q u ac y of a m e dic al d evic e wit h r es p ect t o its i d e ntit y, 
q u alit y, d ur a bilit y, r eli a bility, us a bilit y, s af et y or p erf or m a nc e.  
N ot e 1: D D i ncl u d e m alf u ncti o ns, us e err ors a n d i n a d e q u ac y i n 
t h e i nf or m ati o n s u p pli e d by t h e m a n uf act ur er i ncl u di n g l a b eli n g.  
N ot e 2: T his d efi niti o n i ncl u d es d e vic e d efici e nci es r el at e d t o t h e 
i nv esti g ati o n al m e dic al d evic e or t h e c o m p ar at or. (I S O 
1 4 1 5 5: 2 0 2 0, 3. 1 9)  
 
R el at e d n ess  
D evic e r el at e d  
( T h os e cl assifi e d as 
I nv esti g ati o n al i n T a bl e 3) 
A n a dv ers e ev e nt t h at r es ults fr o m t h e pr es e nc e or p erf or m a nc e 
(i nt e n d e d or ot h er wis e) of t h e I nv esti g ati o n al c o m p o n e nts of 
I nc e pti v syst e m. 
•  
I nc e pti v I N S 
•  
V ectris S ur e Sc a n M RI l e a ds  
•  
S p ecif y S ur e Sc a n M RI 5 - 6-5 l e a ds  
•  
Cli nici a n T a bl et  
•  
Cli nici a n Pr o gr a m m er A p pl ic ati o n 
•  
Sti m ul ati o n Tri ali n g Cli nici a n Pr o gr a m m er A p plic ati o n  
•  
Pr o gr a m m er Pl atf or m S oft w ar e -C o m m u nic ati o n M a n a g er 
A p plic ati o n  
•  
P ati e nt D at a S ervic e A p plic ati o n  
•  
P ati e nt H a n ds et  
•  
P ati e nt Pr o gr a m m er A p plic ati o n  
•  
P ati e nt Pr o gr a m m er Tri ali n g A p plic ati o n  
•  
P ati e nt T el e m etry C o m m u nic at or  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 0  of 1 1 7  
 
 
 
 
 
•  
R ec h ar g er A p plic ati o n  
•  
R ec h ar g er  
Pr oc e d ur e R el at e d  
A n a dv ers e ev e nt t h at occ urs d u e t o a ny pr oc e d ur e r el at e d t o t h e 
tri al, i m pl a nt, ex pl a nt or s ur gic al m o dific ati o n of t h e I nc e pti v 
s yst e m or a ny of t h e I nc e pti v s yst e m c o m p o n e nts. 
T h er a py R el at e d  
A n a dv ers e ev e nt t h at occ urs d u e t o t h e t h er a py d eliv er e d by t h e 
I nc e pti v syst e m, s h o ul d n ot i ncl u d e ev e nts t h at r es ult e d fr o m a 
m alf u ncti o n of t h e d e vic e (i. e. h ar d w ar e -r el at e d e v e nts). 
N ot R el at e d  
R el ati o ns hi p t o t h e d e vic e or pr oc e d ur es c a n b e excl u d e d w h e n:  
  t h e ev e nt h as n o t e m p or al r el ati o ns hi p wit h t h e us e of t h e 
d e vic e or pr oc e d ur e  
  t h e ev e nt d o es n ot f oll o w a k n o w n r es p o ns e p att er n t o t h e  
d e vic e (if t h e r es p o ns e p att er n is pr evi o usly k n o w n) a n d is 
bi ol o gic ally i m pl a usi bl e;  
  t h e disc o nti n u ati o n of  d evic e a p plic ati o n or t h e r e d ucti o n 
of t h e l ev el of acti v ati o n/ ex p os ur e - w h e n cli nic ally f e asi bl e 
– a n d r ei ntr o d ucti o n of its us e ( or i ncr e as e of t h e l ev el of 
acti v ati o n/ ex p os ur e), d o n ot i m p act o n t h e e v e nt;  
  t h e ev e nt i nv ol v es a b o dy-sit e or a n or g a n n ot ex p ect e d t o 
b e aff ect e d by t h e d e vic e or pr oc e d ur e;  
  t h e ev e nt c a n b e attri b ut e d t o a n ot h er c a us e ( e. g. a n 
u n d erl yi n g or c o nc urr e nt ill n ess/ cli nic al c o n diti o n, a n 
eff ect of a n ot h er d evic e, dr u g, tr e at m e nt or ot h er risk 
f act ors); 
  t h e ev e nt d o es n ot d e p e n d o n a f als e r es ult giv e n by t h e 
d e vic e us e d f or di a g n osis, w h e n a p plic a bl e;   
I n or d er t o est a blis h t h e n o n-r el at e d n ess, n ot all t h e crit eri a list e d 
a b o v e mi g ht b e m et at t h e s a m e ti m e, d e p e n di n g o n t h e t y p e of 
d e vic e/ pr oc e d ur es a n d t h e s eri o us ev e nt  
P ossi bl e  
T h e r el ati o ns hi p is w e ak b ut c a n n ot b e r ul e d o ut c o m pl et el y. 
Alt er n ati v e c a us es ar e als o p ossi bl e ( e. g. a n u n d erl yi n g or 
c o nc urr e nt ill n ess/ cli nic al c o n diti o n or/ a n d a n eff ect of a n ot h er 
d e vic e, dr u g or tr e at m e nt). C as es w er e r el at e d n ess c a n n ot b e 
ass ess e d or n o i nf or m ati o n h as b e e n o bt ai n e d s h o ul d als o b e 
cl assifi e d as p ossi bl e. 
Pr o b a bl e  
T h e r el ati o ns hi p s e e ms r el e v a nt a n d/ or t h e ev e nt c a n n ot 
r e as o n a bly b e ex pl ai n e d by a n ot h er c a us e. 
C a us al r el ati o ns hi p 
T h e ev e nt is ass oci at e d wit h t h e d evic e or st u dy pr oc e d ur es b e y o n d 
r e as o n a bl e d o u bt w h e n: 
  t h e ev e nt is a k n o w n si d e eff ect of t h e pr o d uct c at e g or y t h e 
d e vic e b el o n gs t o or of si mil ar d e vic es a n d pr oc e d ur es;  
  t h e ev e nt h as a t e m p or al r el ati o ns hip wit h d evic e 
us e/ a p plic ati o n or pr oc e d ur es;  
  t h e ev e nt i nv ol v es a b o dy-sit e or or g a n t h at 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 1  of 1 1 7  
 
 
 
 
 
 
t h e d evic e or pr oc e d ur es ar e a p pli e d t o; 
 
t h e d evic e or pr oc e d ur es h a v e a n eff ect o n; 
  t h e ev e nt f oll o ws a k n o w n r es p o ns e p att er n t o t h e d evic e 
(if t h e r es p o ns e p att er n is pr e vi o usly k n o w n);  
  t h e disc o nti n u ati o n of d e vic e a p plic ati o n ( or r e d ucti o n of 
t h e l ev el of acti v ati o n/ ex p os ur e) a n d r ei ntr o d ucti o n of its 
us e ( or i ncr e as e of t h e l ev el of acti v ati o n/ ex p os ur e), i m p act 
o n t h e  ev e nt ( w h e n cli nic all y f e asi bl e);  
  ot h er p ossi bl e c a us es ( e. g. a n u n d erl yi n g or c o nc urr e nt 
ill n ess/ cli nic al c o n diti o n or/ a n d a n eff ect of a n ot h er 
d e vic e, dr u g or tr e at m e nt) h a v e b e e n a d e q u at el y r ul e d o ut;  
  h ar m t o t h e s u bj ect is d u e t o err or i n us e;  
  t h e ev e nt d e p e n ds o n a f als e r es ult gi v e n by t h e d evic e 
us e d f or di a g n osis, w h e n a p plic a bl e;  
I n or d er t o est a blis h t h e r el at e d n ess, n ot all t h e crit eri a list e d a b o v e 
mi g ht b e m et at t h e s a m e ti m e, d e p e n di n g o n t h e ty p e of 
d e vic e/ pr oc e d ur es a n d t h e  ev e nt.  
S eri o us n ess  
S eri o us A dv ers e Ev e nt ( S A E)  
 
A E t h at l e d t o a ny of t h e f oll o wi n g:  
a)  d e at h,  
b)  s eri o us d et eri or ati o n i n t h e h e alt h of t h e s u bj ect, us ers or 
ot h er p ers o ns as d efi n e d by o n e or m or e of t h e f oll o wi n g:  
1.  A lif e -t hr e at e ni n g ill n ess or i nj ur y, or  
2.  A p er m a n e nt i m p air m e nt of a b o dy str uct ur e or a b o dy 
f u ncti o n, i ncl u di n g c hr o nic dis e as e, or  
3.  I n-p ati e nt or pr ol o n g e d h os pit aliz ati o n, or  
4.  M e dic al or s ur gic al i nt erv e nti o n t o pr ev e nt lif e -
t hr e at e ni n g ill n ess or i nj ur y or p er m a n e nt i m p air m e nt t o 
a b o dy str uct ur e or a b o dy f u ncti o n,  
c) f et al distr ess, f et al d e at h or a c o n g e nit al a b n or m alit y or birt h 
d ef ect i ncl u di n g p hysic al or m e nt al i m p air m e nt.  
N ot e 1: Pl a n n e d h os pit aliz ati o n f or pr e -existi n g c o n diti o n, or a 
pr oc e d ur e r e q uir e d by t h e CI P, wit h o ut s eri o us d et eri or ati o n i n 
h e al t h, is n ot c o nsi d er e d a n S A E.  
(I S O 1 4 1 5 5: 2 0 2 0, 3. 4 5)  
S eri o us A dv ers e D e vic e Eff ect 
( S A D E)  
 
A dv ers e d e vic e eff ect t h at h as r es ult e d i n a ny of t h e c o ns e q u e nc es 
c h ar act eristic of a s eri o us a dv ers e ev e nt.  
(I S O 1 4 1 5 5: 2 0 2 0, 3. 4 4)  
U n a ntici p at e d S eri o us A dv ers e 
D evic e Eff ect ( U S A D E)  
 
S eri o us a dv ers e d evic e eff ect w hic h by its n at ur e, i nci d e nc e, 
s e v erit y or o utc o m e h as n ot b e e n i d e ntifi e d i n t h e c urr e nt v ersi o n 
of t h e ris k ass ess m e nt.  
N ot e 1: A ntici p at e d s eri o us a dv ers e d evic e eff ect ( A S A D E) is a n 
eff ect w hic h by n at ur e, i nci d e nc e, s e v erit y or o utc o m e h as b e e n 
i d e ntifi e d i n t h e ris k ass ess m e nt.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 2  of 1 1 7  
 
 
 
 
 
(I S O 1 4 1 5 5: 2 0 2 0 3. 5 1)  
Si g nific a nt S af et y Iss u e ( S SI)  
A s af ety iss u e t h at c o ul d a dv ers el y aff ect t h e s af ety of p artici p a nts 
or m at eri all y i m p act o n t h e c o nti n u e d et hic al acc e pt a bilit y or 
c o n d uct of t h e tri al.  
( N H M R C S af et y m o nit ori n g a n d r e p orti n g i n cli nic al tri als i nv ol vi n g 
t h er a p e utic g o o ds N ov e m b er 2 0 1 6) 
Ur g e nt S af et y M e as ur e ( U S M)  
A m e as ur e r e q uir e d t o b e t a k e n i n or d er t o eli mi n at e a n i m m e di at e 
h az ar d t o a p artici p a nt’s h e alt h or s af ety. 
 
N ot e: T his t y p e of si g nific a nt s af ety iss u e c a n b e i nsti g at e d by eit h er 
t h e i nv esti g at or or s p o ns or a n d c a n b e i m pl e m e nt e d b ef or e s e e ki n g 
a p pr o v al fr o m E Cs or i nstit uti o ns.  
( N H M R C S af et y m o nit ori n g a n d r e p orti n g i n cli nic al tri als i nv ol vi n g 
t h er a pe utic g o o ds N ov e m b er 2 0 1 6)  
S eri o us H e alt h T hr e at  
 
Si g n al fr o m a ny a dv ers e ev e nt or d evic e d efici e ncy t h at i n dic at es a n 
i m mi n e nt risk of d e at h or a s eri o us d et eri or ati o n i n t h e h e alt h i n 
s u bj ects, us ers or ot h er p ers o ns, a n d t h at r e q uir es pr o m pt r e m e di al 
acti o n f or ot h er s u bj ects, us ers or ot h er p ers o ns  
N O T E 1: T his w o ul d i ncl u d e e v e nts t h at ar e of si g nific a nt a n d 
u n ex p ect e d n at ur e s uc h t h at t h ey b ec o m e al ar mi n g as a p ot e nti al 
s eri o us h e alt h h az ar d or p ossi bilit y of m ulti pl e d e at hs occ urri n g at 
s h ort i nt er v als.  
(I S O 1 4 1 5 5: 2 0 2 0, 3. 4 6)  
U n av oi d a bl e A dv ers e E v e nts 
( U A E) 
A n A dv ers e Ev e nt i n h er e nt t o a s ur gic al pr oc e d ur e t h at is ex p ect e d 
t o occ ur i n all s u bj ects f or a pr oj ect e d d ur ati o n acc or di n g t o t h e 
I nv esti g at or’s o pi ni o n.  
U n a v oi d a bl e A Es ar e n ot c o nsi d er e d r e p ort a bl e u nl ess t h e A E 
w ors e ns or is pr es e nt o utsi d e t h e st at e d ti m efr a m e.  
Incl u di n g,  b ut n ot li mit e d t o:  
D escri pti o n  
Ti m efr a m e ( h o urs) 
fr o m t h e S ur gic al 
Pr oc e d ur e  
A n est h esi a r el at e d n a us e a / v o miti n g  
2 4  
L o w-gr a d e f ev er ( < 1 0 0⁰ F or < 3 7. 8⁰ C)  
4 8  
P ai n at t h e acc ess sit e  
7 2  
Mil d t o m o d er at e br uisi n g / ecc hy m osis  
1 6 8  
Sl e e p pr o bl e ms (i ns o m ni a)  
7 2  
B ac k p ai n r el at e d t o l yi n g o n t a bl e  
7 2  
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 3  of 1 1 7  
 
 
 
 
 
1 2. 5  R e p orti n g of A d v er s e E v e nt s  a n d D e vi c e D efi ci e n ci e s  
All r e p ort a bl e A Es a n d d e vic e d efici e nci es m ust b e r ec or d e d i n t h e s u bj ect’s m e dic al r ec or d, t h e C R F a n d 
pr o m ptly t o M e dtr o nic.  I nv esti g at ors ar e r e q uir e d t o k e e p r ec or ds o n all r el e v a nt o bs er v ati o ns.  
R e p ort a bl e a dv ers e ev e nts a n d d e vic e d efici e nci es will i ncl u d e t h e f oll o wi n g i nf or m ati o n, at a mi ni m u m:  
•  
D at e of ev e nt  
•  
Di a g n osis or d escri pti o n of t h e ev e nt  
•  
Ass ess m e nt of t h e s eri o us n ess a n d r el ati o ns hi p t o t h e pr o d uct(s) u n d er i nv esti g ati o n a n d 
pr oc e d ur e ( A E o nl y)  
•  
M o d el a n d i d e ntifi ers (s eri al, l ot n u m b er) f or t h e i nv ol v e d d evic e (if a p plic a bl e)  
•  
Tr e at m e nt ( A E  o nl y)  
•  
O utc o m e a n d d at e of r es ol uti o n ( A E o nl y)  
It is t h e r es p o nsi bilit y of t h e I nv esti g at or t o i d e ntif y t h e occ urr e nc e of r e p ort a bl e A Es a n d d e vic e 
d efici e nci es a n d t o e ns ur e t h e r e q uir e d i nf or m ati o n is acc ur at ely d oc u m e nt e d o n t h e C R F.  
1 2. 5. 1  
A d v er s e E v e nt a n d D e vi c e D efi ci e n c y Cl a s sifi c ati o n  
All A E s a n d d evic e d efici e nci es will b e r e vi e w e d by a M e dtr o nic r e pr es e nt ati v e. A Es will b e cl assifi e d 
acc or di n g t o t h e d efi niti o ns pr ovi d e d.  
U p o n r ec ei pt of A E/ d evic e d efici e nci es  at M e dtr o nic, a M e dtr o nic r e pr es e nt ativ e  will r evi e w t h e A E/ 
d e vic e d efici e nci es  f or c o m pl et e n ess a n d acc ur acy a n d w h e n n ec ess ary will r e q u est cl arific ati o n a n d/ or 
a d diti o n al i nf or m ati o n fr o m t h e I nv esti g at or. M e dtr o nic will utiliz e M e d D R A f or R e g ul at ory Acti viti es, t o 
assi g n a M e d D R A t er m f or e ac h A E/ d evic e d efici e nci es  b as e d o n t h e i nf or m ati o n pr o vi d e d by t h e 
i nv esti g at or. C o pi es of d e-i d e ntifi e d s o urc e d oc u m e nt ati o n r e g ar di n g a n a dv ers e e v e nt or d evic e 
d efici e nc y ( e . g., cli nici a n n ot es or s u m m ari es) will b e pr o vi d e d t o M e dtr o nic u p o n r e q u est.  
R e g ul at ory r e p orti n g of A Es a n d d e vic e d efici e nci es  will b e c o m pl et e d acc or di n g t o l oc al r e g ul at or y 
r e q uir e m e nts. R ef er t o T a bl e 9  f or a list of r e q uir e d i nv esti g at or a n d M e dtr o nic r e p orti n g r e q uir e m e nts 
a n d ti m efr a m es. It is t h e r es p o nsi bilit y of b ot h t o a bi d e by a ny a d diti o n al A E r e p orti n g r e q uir e m e nts 
sti p ul at e d by t h e E C r es p o nsi bl e f or ov ersi g ht of t h e st u dy.  
F or e m er g e nc y c o nt act r e g ar di n g a U S A D E, S A E a n d/ or S A D E, c o nt act a st u dy r e pr es e nt ativ e 
i m m e di at ely (r ef er t o t h e st u dy c o nt act list pr o vi d e d i n t h e st u dy sit e’s st u dy d oc u m e nts 
bi n d er/i nv esti g at or sit e fil e or  r ef er t o t h e S p o ns or c o nt act i nf or m ati o n pr ovi d e d o n t h e titl e p a g e).  
A Es will b e cl assifi e d acc or di n g t o t h e st a n d ar d d efi niti o ns as o utli n e d b el o w i n T a bl e 8 . 
T a bl e  8: E v e nt Cl a s sifi c ati o n R e s p o n si biliti e s 
W h at is Cl assifi e d  
W h o Cl assifi es  
Cl assific ati o n  
R el at e d n ess *  
I nv esti g at or, S p o ns or  
•  
R el ati o ns hi p t o t h e:  
o  D evic e : 
 
I nc e pti v I N S 
 
V ectris S ur e Sc a n M RI 
l e a ds 
 
S p ecif y S ur e Sc a n M RI 
5 -6 -5 l e a ds  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 4  of 1 1 7  
 
 
 
 
 
W h at is Cl assifi e d  
W h o Cl assifi es  
Cl assific ati o n  
 
Cli nici a n T a bl et  
 
Cli nici a n Pr o gr a m m er 
A p plic ati o n  
 
Sti m ul ati o n Tri ali n g 
Cli nici a n Pr o gr a m m er 
A p plic ati o n  
 
Pr o gr a m m er Pl atf or m 
S oft w ar e -
C o m m u nic ati o n 
M a n a g er A p plic ati o n  
 
P ati e nt D at a S ervic e 
A p plic ati o n  
 
P ati e nt H a n ds et  
 
P ati e nt Pr o gr a m m er 
A p plic ati o n  
 
P ati e nt Pr o gr a m m er 
Tri ali n g A p plic ati o n  
 
P ati e nt T el e m etry 
C o m m u nic at or  
 
R ec h ar g er A p plic ati o n  
 
R ec h ar g er  
o  Pr oc e d ur e  
o  T h er a py  
Ex p ect e d n ess  
S p o ns or  
U S A D E  
S eri o us n ess  
I nv esti g at or 
S A E, d e vic e d efici e nci es  wit h 
S A D E p ot e nti al  
S p o ns or  
S A E, d e vic e d efici e nci es  wit h 
S A D E p ot e nti al  
Di a g n osis  
I nv esti g at or 
B as e d o n pr es e nti n g si g ns a n d 
s y m pt o ms a n d ot h er s u p p orti n g 
d at a  
S p o ns or  
M e d D R A t er m assi g n e d b as e d 
o n t h e d at a pr o vi d e d by 
I nv esti g at or 
* A dv ers e ev e nts t h at ar e cl assifi e d as h avi n g a r el a ti o ns hi p of p ossi bl e , pr o b a bl e or c a us al t o t h e 
i nv esti g ati o n al d evic e or pr oc e d ur e  or t h er a py  ar e c o nsi d er e d t o b e r el at e d t o t h e i nv esti g ati o n al 
m e dic al d e vic e a n d ar e cl assifi e d as A D Es.  
1 2. 5. 2  
A d v er s e E v e nt a n d D e vi c e D efi ci e n c y R e p orti n g R e q uir e m e nt s  
R e g ul at ory r e p orti n g of A Es a n d d e vic e d efici e nci es will b e r ec or d e d a n d r e p ort e d acc or di n g t o l oc al 
r e g ul at ory r e q uir e m e nts. It is t h e r es p o nsi bilit y of t h e I nv esti g at or a n d t h e s p o ns or t o a bi d e by t h e A E 
r e p orti n g r e q uir e m e nts sti p ul at e d by l oc al l a w a n d t h e st u dy sit e’s E C.  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 5  of 1 1 7  
 
 
 
 
 
T a bl e 9 : R e p orti n g R e q uir e m e nt s 
All S A Es a n d D Ds wit h p ot e nti al S A D E  
I n v esti g at or s u b mit t o: 
M e dtr o nic  
 Wit h o ut u nj ustifi e d d el a y.  
 ( N H M R C S af ety m o nit ori n g a n d r e p orti n g i n 
cli nic al tri als i nv olvi n g t h er a p e utic g o o ds 
N o v e m b er 2 0 1 6 s ecti o n C. 2. b)  
Et hics C o m mitt e e  
S u b mit p er l oc al r e p orti n g r e q uir e m e nts.  
I nstit uti o n 
S u b mit t o I nstit uti o n p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory a ut h oriti es  
S u b mit p er l oc al r e p orti n g r e q uir e m e nts.  
S p o ns or s u b mit t o:  
I nv esti g at ors 
S u b mit t o i nv esti g at or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory a ut h oriti es  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
U n a ntici p at e d S eri o us A d v ers e D e vic e Eff ects ( U S A D Es)  
I n v esti g at or s u b mit t o: 
M e dtr o nic  
S u b mit t o t h e s p o ns or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory A ut h orit y  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e, I nstit uti o n  
 R e p ort t o t h eir i nstit uti o n wit h o ut u n d u e d el a y 
a n d n o l at er t h a n 7 2 h o urs of t h e Pri nci p al 
I nv esti g at or b ec o mi n g a w ar e of t h e e v e nt. 
( N H M R C S af et y m o nit ori n g a n d r e p orti n g i n 
cli nic al tri als i nv olvi n g t h er a p e utic g o o ds 
N o v e m b er 2 0 1 6 s ecti o n C. 2. g)  
S p o ns or s u b mit t o:  
I nv esti g at or 
S u b mit t o t h e i nv esti g at or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory a ut h oriti es  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
Si g nific a nt S af et y Iss u es ( S SI) a n d Ur g e nt S af et y M e as ur e ( U S M)  
I n v esti g at or s u b mit t o: 
 
M e dtr o nic , Et hics C o m mitt e e, I nstit uti o n 
 
•  
 Ur g e nt S af et y M e as ur e ( US Ms): Wit hi n 
2 4 h o urs  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 6  of 1 1 7  
 
 
 
 
 
( N H M R C S af et y m o nit ori n g a n d r e p orti n g 
i n cli nic al tri als i nv olvi n g t h er a p e utic 
g o o ds N o v e m b er 2 0 1 6 s ecti o n C. 2.c)  
•  
All ot h er si g nific a nt s af ety iss u es: wit h o ut 
u n d u e d el a y a n d n o l at er t h a n 7 2 h o urs 
of t h e pri nci p al i nv esti g at or b ec o mi n g 
a w ar e of t h e ev e nt  
( N H M R C S af et y m o nit ori n g a n d r e p orti n g 
i n cli nic al tri als i nv olvi n g t h er a p e utic 
g o o ds N o v e m b er 2 0 1 6 s ecti o n C. 2. g)  
R e g ul at ory A ut h orit y  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
I nstit uti o n 
S u b mit t o I nstit uti o n p er l oc al r e p orti n g 
r e q uir e m e nts. 
S p o ns or s u b mit t o:  
I nv esti g at or 
S u b mit t o t h e i nv esti g at or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory a ut h oriti es  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
I nstit uti o n 
S u b mit t o I nstit uti o n p er l oc al r e p orti n g 
r e q uir e m e nts. 
All ot h er r e p ort a bl e A Es  
I n v esti g at or s u b mit t o: 
M e dtr o nic  
S u b mit t o t h e s p o ns or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory A ut h orit y  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
S p o ns or s u b mit t o:  
R e g ul at ory a ut h oriti es  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
All ot h er D e vic e D efici e nci es  
I n v esti g at or s u b mit t o: 
M e dtr o nic  
S u b mit t o t h e s p o ns or p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory A ut h orit y  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
N e w i nf or m ati o n t h at m a y a d v ers el y aff ect s af et y of t h e s u bj ects or t h e c o n d uct of t h e st u d y  
I n v esti g at or s u b mit t o: 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 7  of 1 1 7  
 
 
 
 
 
M e dtr o nic  
S u b mit t o t h e s p o ns or p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
S p o ns or s u b mit t o:  
I nv esti g at or 
S u b mit t o i nv esti g at ors p er l oc al r e p orti n g 
r e q uir e m e nts. 
R e g ul at ory a ut h oriti es  
S u b mit t o r e g ul at ory a ut h orit y p er l oc al r e p orti n g 
r e q uir e m e nts. 
Et hics C o m mitt e e  
S u b mit t o E C p er l oc al r e p orti n g r e q uir e m e nts.  
 
1 2. 6  S u bj e ct D e at h  
All s u bj ect d e at hs m ust b e r e p ort e d by t h e i nv esti g at or t o M e dtr o nic o n a n A E f or m ( A E wit h o utc o m e of 
f at al) as s o o n as p ossi bl e aft er t h e i nv esti g at or first l e ar ns of t h e d e at h.  I n c as e of d e at h, t h er e s h o ul d 
b e o nl y o n e A E wit h t h e o utc o m e of d e at h.  
In t h e ev e nt of a s u bj ect’s d e at h, it is r ec o m m e n d e d t h at t h e i m pl a nt e d s yst e m b e ex pl a nt e d a n d 
r et ur n e d t o M e dtr o nic f or a n al ysis w h e n ev er p ossi bl e p er l oc al pr oc ess. L oc al l a ws a n d pr oc e d ur es m ust 
b e f oll o w e d w h er e a p plic a bl e. If a ny syst e m c o m p o n e nt is r et ur n e d t o M e dtr o nic, i nt er n al r et ur n 
pr o d uct r e p orti n g syst e ms m a y b e us e d t o g at h er a d diti o n al i nf or m ati o n a b o ut t h e r et ur n e d 
d e vic e/c o m p o n e nt.  
A c o py of t h e d e at h c ertific at e, if a v ail a bl e a n d all o w e d by st at e/l oc al l a w, s h o ul d b e s e nt t o t h e 
M e dtr o nic cli nic al st u dy t e a m. W h e n a d e at h occ urs i n a h os pit al, a c o py of t h e d e at h s u m m ary r e p ort 
a n d all r el ev a nt h os pit al r ec or ds, if a v ail a bl e s h o ul d b e s e nt t o t h e M e dtr o nic cli nic al st u dy t e a m. If a n 
a ut o ps y is c o n d uct e d, a c o py of t h e a ut o psy r e p ort s h o ul d als o b e s e nt t o t h e M e dtr o nic cli nic al st u dy 
t e a m if av ail a bl e a n d all o w e d by st at e/l oc al l a w. W h e n t h e d e at h occ urs at a r e m ot e st u dy sit e, it is t h e 
i nv esti g ativ e st u dy sit e’s r es p o nsi bilit y t o att e m pt r etri e v al of i nf or m ati o n a b o ut t h e d e at h. A d diti o n all y, 
d e vic e dis p ositi o n i nf or m ati o n s h o ul d b e u p d at e d.  
I n s u m m ar y, t h e f oll o wi n g d at a will b e c oll ect e d: 
•  
D at e of d e at h  
•  
D et ail e d d escri pti o n of d e at h  
•  
C a us e of d e at h  
•  
R el at e d n ess t o d evic e, t h er a py  a n d/ or pr oc e d ur e  
•  
D evic e i nt err o g ati o n i nf or m ati o n/r e p orts (if av ail a bl e a n d all o w e d by st at e/l oc al l a w) 
•  
D evic e dis p ositi o n i nf or m ati o n  
•  
D e at h s u m m ary/ h os pit al r ec or ds (if av ail a bl e a n d all o w e d by st at e/l oc al l a w)  
•  
A ut o ps y r e p ort (if a v ail a bl e a n d all o w e d by st at e/l oc al l a w)  
•  
D e at h c ertific at e (if  av ail a bl e a n d all o w e d by st at e/l oc al l a w)  
1 2. 7  Pr o d u ct C o m pl ai nt R e p orti n g  
It is t h e r es p o nsi bilit y of t h e Inv esti g at or t o r e p ort all pr o d uct c o m pl ai nt(s) ass oci at e d wit h a m e dic al 
d e vic e distri b ut e d by M e dtr o nic, r e g ar dl ess w h et h er t h e y ar e r el at e d t o i nt e n d e d us e, mis us e or a b us e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 8  of 1 1 7  
 
 
 
 
 
of t h e pr o d uct.  R e p orti n g m ust b e d o n e i m m e di at ely a n d vi a t h e r e g ul ar c h a n n els f or m ark et -r el e as e d 
pr o d ucts.  T h e r e p orti n g of pr o d uct c o m pl ai nts by t h e cli nic al t e a m m ust b e d o n e acc or di n g t o t h e l oc al 
St a n d ar d O p er ati n g Pr oc e d ur e s.  M e dtr o nic will n otify t h e R e g ul at ory A ut h ority , as a p plic a bl e , f or t h e 
f oll o wi n g i nci d e nts i m m e di at el y u p o n l e ar ni n g of t h e m a n d is n ot li mit e d t o A Es a n d d e vic e d efici e nci es 
o nl y:  
•  
A ny m alf u ncti o n or d et eri or ati o n i n t h e c h ar act eristics a n d/ or p erf or m a nc e of a d e vic e, 
as w ell as a ny i n a d e q u ac y i n t h e l a b eli n g or i nstr ucti o ns f or us e w hic h l e d or mi g ht h a v e 
l e d t o t h e d e at h or s eri o us d et eri or ati o n i n t h e st at e of h e alt h of a p ati e nt, us er, or 
ot h er p ers o n.  
•  
A ny t ec h nic al or m e dic al r e as o n r es ulti n g i n wit h dr a w al of a d e vic e fr o m t h e m ark et by 
t h e m a n uf act ur er. 
•  
A ny s eri o us d et eri or ati o n i n t h e st at e of h e alt h, i ncl u di n g:  
 
Lif e-t hr e at e ni n g ill n ess or i nj ur y 
 
P er m a n e nt i m p air m e nt of a b o dy f u ncti o n or p er m a n e nt d a m a g e t o a b o dy 
str uct ur e 
 
A c o n diti o n n e c essit ati n g m e dic al or s ur gic al i nt erv e nti o n t o pr ev e nt p er m a n e nt 
i m p air m e nt of a b o dy f u ncti o n or p er m a n e nt d a m a g e t o a b o dy str uct ur e 
1 3.  C o m mitt e e s  a n d Or g a ni z ati o n s  
1 3. 1  C li ni c al R e s e ar c h O r g a ni z ati o n ( C R O ) 
C R Os will n ot b e us e d i n t his st u dy.  
1 3. 2  D at a M o nit ori n g C o m mitt e e ( D M C)  
A D M C is n ot n e e d e d f or t his st u dy.   I nst e a d, r e g ul ar m e eti n gs will b e h el d by S p o ns or p ers o n n el, 
i ncl u di n g t h e M e dic al A dvis or, t o r e vi e w A Es a n d d evic e d efici e nci es, i d e ntif y p ot e nti al tr e n ds i n s af et y 
d at a d uri n g t h e cli nic al st u dy, a n d t o e ns ur e c o nsist e nt r e p orti n g.  
1 4.  St ati sti c al D e si g n a n d M et h o d s  
T his s ecti o n pr es e nts st atistic al c o nsi d er ati o ns f or t h e st u dy d esi g n a n d pr o vi d es a hi g h -l e v el d escri pti o n 
of pl a n n e d a n al ysis a n d r e p orti n g. M or e d et ails will b e gi v e n i n a s e p ar at e St atistic al A n al ysis Pl a n ( S A P ) 
t h at will b e a p pr ov e d b ef or e d at a fr e ez e or l ock  f or a n al ysis. A ny d e vi ati o n t o t h e pr e-s p ecifi e d st atistic al 
a n al ys es will b e n ot e d i n t h e st u dy r e p ort.  
1 4. 1  G e n er al A s p e ct s of A n al y si s  
D at a a n alysis will b e p erf or m e d by M e dtr o nic -e m pl oy e d st atistici a ns or d esi g n e es. A v ali d at e d st atistic al 
s oft w are p ac k a g e ( e. g., S A S v ersi o n 9. 4 or hi g h er) will b e us e d t o a n alyz e t h e st u dy r es ults.  
G e n er al d escri pti v e  st atistics f or c at e g oric al a n d c o nti n u o us v ari a bl es will b e us e d : cat e g oric al v ari a bl es 
will b e s u m m ariz e d as c o u nts a n d p erc e nt a g es ; co nti n u o us v ari a bl es will b e pr es e nt e d usi n g m e a n, 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 6 9  of 1 1 7  
 
 
 
 
 
st a n d ar d d e vi ati o n, m e di a n, q u artil es a n d r a n g e, as a p plic a bl e.  All c o nfi d e nc e i nt er v als will b e pr es e nt e d 
as t w o -si d e d 9 5 % c o nfi d e nc e i nt erv als, u nl ess ot h er wis e pr e-s p ecifi e d. 
1 4. 1. 1  
A n al y si s S et s  
•  
T h e All C o ns e nt e d S et  (A C S) will i ncl u d e all s u bj ects w h o si g n e d t h e st u dy s p ecific I C F a n d e nr oll e d 
i n t h e st u dy.  
•  
T h e F ull A n al ysis S et  ( F A S) will i ncl u d e all d evic e -i m pl a nt e d s u bj ects.  
•  
T h e Pri m ar y A n al ysis S et  (P A S ) will f oll o w t h e i nt e nt-t o-tr e at (I T T) pri nci pl e t o i ncl u d e r a n d o miz e d 
l o w-b ack  a n d / or l e g p ai n s u bj ects w h o will b e us e d f or t h e  pri m ar y o bj ectiv e , i. e., t h e first 2 8 
r a n d o miz e d l o w-b ac k a n d / or l e g p ai n s u bj ects w h o pr o vi d e t h e pri m ary e n d p oi nt .  
•  
T h e C o m pl et e C as e S et  ( C CS ) will i ncl u d e all d e vic e -i m pl a nt e d s u bj ects w h o h a v e d at a a v ail a bl e at 
b as eli n e a n d f oll o w -u p. T his s et is d efi n e d f or e ac h o utc o m e m e as ur e at e ac h f oll o w -u p visit . 
 
1 4. 1. 2  
H a n dli n g Mi s si n g D at a  
Missi n g d at a ar e a p ot e nti al s o urc e of bi as w h e n a n al yzi n g st u dy d at a. A ri g or o us st u dy d esi g n a n d 
ex ec uti o n will h el p pr ev e nt t h e i nci d e nc e of missi n g d at a fr o m occ urri n g  as d escri b e d i n  S ecti o n 1 4 . 9. 
T h e pri m ar y o bj ecti v e  will us e t h e P A S  wit h t h e M ulti pl e I m p ut ati o n ( MI) m et h o d ol o gy f or missi n g d at a  
if t h er e is gr e at er t h a n 5 % of s u bj ects wit h missi n g v al u es . D et ails of t h e i m p ut ati o n m et h o d ar e 
d escri b e d i n S ecti o n 1 4. 4. 1. 6 . T h e s ec o n d ar y o bj ecti v es will us e t h e F A S  wit h t h e MI m et h o d ol o gy f or 
missi n g d at a  if t h er e is gr e at er t h a n 5 % of s u bj ects wit h missi n g v al u es, as d escri b e d i n S ecti o ns 1 4. 5. 1. 4  
a n d 1 4. 5. 2. 4 . All ot h er o bj ecti v es will b e a n al yz e d usi n g t h e C C S u nl ess ot h er wis e s p ecifi e d i n t h e S A P . 
T h e A C S a n d F A S  s u bj ects will b e us e d f or d e m o gr a p hic  a n al ys es  a n d s af et y r e p orti n g.   
 
 
 
 
 
 
 
 
 
 
 
  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 0  of 1 1 7  
 
 
 
 
 
1 4. 1. 4  
Di s p o siti o n of S u bj e ct s  
S u bj ect dis p ositi o n will b e ill ustr at e d i n a fl o w di a gr a m. S u bj ect visits will b e t a b ul at e d a n d c o m pli a nc e 
t o visit sc h e d ul e will b e s u m m ariz e d. Attriti o n will b e i d e ntifi e d a n d s u m m ariz e d. 
1 4. 1. 5  
D e m o gr a p hi c s a n d Ot h er B a s eli n e C h ar a ct eri sti c s  
T h e s u bj ects’ b as eli n e d e m o gr a p hics will b e s u m m ariz e d wit h st a n d ar d d escri ptiv e s u m m ary st atistics, 
i ncl u di n g c o u nts a n d p erc e nt a g es f or c at e g oric al v ari a bl es, a n d m e a n, st a n d ar d d e vi ati o n, m e di a n, a n d 
r a n g e f or c o nti n u o us v ari a bl es.  
1 4. 1. 6  
Ot h er C h ar a ct eri sti c s  
T h e s u bj ects’ ot h er c h ar act eristics, s uc h as q u esti o n n air e r es p o ns es, m ay  b e s u m m ariz e d wit h st a n d ar d 
d escri ptiv e s u m m ar y st atistics , i ncl u di n g c o u nts a n d p erc e nt a g es f or c at e g oric al v ari a bl es, a n d m e a n, 
st a n d ar d d e vi ati o n, m e di a n, a n d r a n g e f or c o nti n u o us v ari a bl es.  
1 4. 1. 7  
A dj u sti n g f or M ulti pl e C o m p ari s o n s  
As t h e  o nl y hy p ot h esis t est  i n t his st u dy is f or t h e si n gl e e n d p oi nt of t h e pri m ary o bj ectiv e , a dj ust m e nts 
f or m ulti pl e c o m p aris o ns ar e  n ot r e q uir e d.  
1 4. 2  A n al y si s E x e c uti o n  
T h e  pri m ar y o bj ecti v e  a n alysis will occ ur aft er  2 8  r a n d o miz e d l o w-b ac k a n d / or l e g p ai n s u bj ects fi nis h 
t h e i n-cli nic t esti n g, a n d o n e fi n al st u dy a n al ysis will occ ur aft er all s u bj ects c o m pl et e t h e st u dy. T h e 
p ri m ar y o bj ectiv e a n alysis is d escri b e d i n S ecti o n  1 4. 4 . A fi n al r e p ort will b e pr e p ar e d o nc e all d a t a 
c oll ecti o n h as e n d e d a n d all s u bj ects h av e c o m pl et e d t h e st u dy a n d h av e b e e n exit e d.  
1 4. 3  I nt eri m  A n al y si s  
N o i nt eri m a n alys es will b e p erf or m e d i n t his st u dy. 
1 4. 4  Pri m ar y O bj e cti v e  
T h e pri m ar y  o bj ecti v e is to d e m o nstr at e t h at t h e pr o p orti o n of l o w-b ac k a n d / or l e g p ai n s u bj ects h a vi n g 
a r e d ucti o n i n ov ersti m ul ati o n s e ns ati o n wit h N e ur o S e ns e O n c o m p ar e d t o N e ur o S e ns e Off, at t h e  
r a n d o miz ati o n a n d i n-cli nic t esti n g visit, exc e e ds a p erf or m a nc e g o al of 5 0 %.    
O v er sti m ul ati o n is d efi n e d as a n u nc o mf ort a bl e s e ns ati o n of sti m ul ati o n (i nt e ns e ti n gli n g, s h oc ki n g, 
j olti n g) br o u g ht a b o ut by pr ot oc ol-pr escri b e d activiti es 
. T his 
o v ersti m ul ati o n s e ns ati o n is tr a nsi e nt a n d r ev ers e d by t h e s u bj ect r et ur ni n g t o a n e utr al p ositi o n . 
1 4. 4. 1. 1  
H y p ot h e si s  
It is hy p ot h esiz e d t h at t h e pr o p orti o n of l o w-b ack  a n d / or l e g p ai n s u bj ects wit h a r e d ucti o n i n 
o v ersti m ul ati o n s e ns ati o n d uri n g N e ur o S e ns e O n  c o m p ar e d t o N e ur o S e ns e Off  p eri o d exc e e ds a 
p erf or m a nc e g o al of 5 0 %.  
H 0: p ≤ 5 0 %  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 1  of 1 1 7  
 
 
 
 
 
H A : p > 5 0 % 
1 4. 4. 1. 2  
E n d p oi nt d efi niti o n a n d d eri v ati o n  
F or ev ery o v ersti m ul ati o n s e ns ati o n br o u g ht a b o ut by pr ot oc ol  pr escri b e d activiti es, s u bj ects will r at e 
t h e i nt e nsit y of t h e s e ns ati o n i n t h e f oll o wi n g 5- p oi nt Li k ert sc al e:  
•  
N o ov ersti m ul ati o n s e ns ati o n (c o d e = 0)  
•  
W e a k ov ersti m ul ati o n s e ns ati o n (c o d e = 1)  
•  
M o d er at e ov ersti m ul ati o n s e ns ati o n (c o d e = 2)  
•  
Str o n g ov ersti m ul ati o n s e ns ati o n (c o d e = 3)  
•  
V er y str o n g ov ersti m ul ati o n s e ns ati o n (c o d e = 4)  
T h e av er a g e i nt e nsity sc or es d uri n g N e ur o S e ns e O n a n d N e ur o S e ns e Off p eri o d will b e c alc ul at e d f or 
e ac h i n divi d u al s u bj ect. If t h e a v er a g e i nt e nsit y sc or e d uri n g N e ur o S e ns e O n p eri o d is l ess t h a n t h at 
fr o m t h e N e ur o S e ns e Off p eri o d, t h e s u bj ect is c o nsi d er e d as a s u bj ect wit h a r e d ucti o n i n 
o v ersti m ul ati o n s e ns ati o n d uri n g N e ur o S e ns e O n vs. N e ur o S e ns e Off p eri o d. T h e pr o p orti o n of s u bj ects 
wit h a r e d ucti o n i n ov ersti m ul ati o n s e ns ati o n a m o n g s u bj ects w h o h av e i n cli nic t esti n g n e e d t o exc e e d 
a p erf or m a nc e g o al of 5 0 %.   
1 4. 4. 1. 3  
P erf or m a n c e R e q uir e m e nt s  
T h e n ull hy p ot h esis will b e r ej ect e d if t h e o n e -si d e d 9 7. 5 % l o w er c o nfi d e nc e b o u n d is gr e at er t h a n 5 0 %.  
1 4. 4. 1. 4  
R ati o n al e f or P erf or m a n c e Crit eri a  
T h e N e ur o S e ns e O n  s etti n g is a n a d diti o n al f e at ur e t o c o ntr ol o v ersti m ul ati o n t o b e a d d e d t o a n 
existi n g d evic e. It is ex p ect e d t h at t his f e at ur e will h el p m aj orit y of t h e s u bj ects. T h e 5 0 % p erf or m a nc e 
g o al is s el ect e d t o e ns ur e t h at m aj ority of t h e l o w-b ack  a n d / or l e g p ai n s u bj ects m e et t h e crit eri o n wit h 
9 5 % c o nfi d e nc e.  
1 4. 4. 1. 5  
A n al y si s M et h o d s  
T h e pr o p orti o n of l o w-b ac k a n d / or l e g p ai n s u bj ects wit h a r e d ucti o n i n o v ersti m ul ati o n s e ns ati o n 
d uri n g N e ur o S e ns e O n  c o m p ar e d t o N e ur o S e ns e Off  p eri o d will b e c alc ul at e d, wit h a o n e -si d e d 9 7. 5 % 
c o nfi d e nc e l o w er b o u n d. T his pr o p orti o n will b e t e st e d a g ai nst 5 0 % usi n g a bi n o mi al ex act t est. T h e 
c o nfi d e nc e l o w er b o u n d n e e ds t o b e gr e at er t h a n 5 0 %, or e q ui v al e ntl y, t h e p -v al u e m ust b e  l ess t h a n 
0. 0 2 5 t o r ej ect t h e n ull hy p ot h esis.  
 
 
 
   
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 2  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
   
 
1 4. 4. 1. 6  
D et er mi n ati o n of S u bj e ct s / D at a f or A n al y si s  
T h e a n al ysis f or t his o bj ectiv e will f oll o w t h e I T T pri nci pl e by i ncl u di n g all t h e l o w-b ac k  a n d / or l e g p ai n 
s u bj ects r a n d o miz e d f or t h e pri m ary  a n alysis  (P A S). If t h er e is gr e at er t h a n 5 % of s u bj ects wit h missi n g 
v al u es , t h e n th e s u bj ects w h o ar e r a n d o miz e d b ut h av e missi n g a v er a g e sc ori n g of ov ersti m ul ati o n 
s e ns ati o n d uri n g N e ur o S e ns e O n a n d/ or N e ur o S e ns e Off  p eri o d will b e i m p ut e d usi n g M ulti pl e 
I m p ut ati o n ( MI). Pri or t o t h e us e of MI, t h e distri b uti o ns of t h e c o nti n u o us v ari a bl es will b e ass ess e d f or 
n or m alit y a n d tr a nsf or m ati o n m a y b e c o nsi d er e d if t h e y ar e n ot n or m ally distri b ut e d.  
 
 
 
 
F oll o wi n g i m p ut ati o n, t h e o bj ectiv e will b e ev al u at e d usi n g MI a n al ysis m et h o d.  
 
 
  
1 4. 5  S e c o n d ar y  O bj e cti v e s 
1 4. 5. 1  
S e c o n d ar y O bj e cti v e 1: O v er all  R e s p o n d er R at e s  
T his o bj ectiv e  is to c h ar act eriz e t h e effic ac y of s pi n al c or d sti m ul ati o n ( S C S) t h er a py f or t h e tr e at m e nt of 
o v er all p ai n (f or l o w -b ack a n d / or l e g p ai n s u bj ects) by e v al u ati n g t h e effic ac y r es p o n d er r at e. T h e 
effic ac y r es p o n d er r at e is d ef i n e d as t h e p erc e nt a g e of i m pl a nt e d s u bj ects w h o ex p eri e nc e at l e ast a 
5 0 % i m pr ov e m e nt i n ov er all p ai n, as m e as ur e d by t h e Vis u al A n al o g u e Sc al e ( V A S), fr o m B as eli n e t o t h e 
3- M o nt h Visit.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 3  of 1 1 7  
 
 
 
 
 
1 4. 5. 1. 1  
H y p ot h e si s  
T h er e is n o hy p ot h esis t est f or t h is o bj ectiv e. T h e p ur p o s e is t o c h ar act eriz e t h e ov er all effic acy 
r es p o n d er r at e at t h e 3-M o nt h Visit.  
1 4. 5. 1. 2  
E n d p oi nt d efi niti o n a n d d eri v ati o n  
A r es p o n d er will b e a ny l o w-b ac k a n d / or l e g p ai n s u bj ect w h o d e m o nstr at es at l e ast a 5 0 % i m pr o v e m e nt 
( p erc e nt c h a n g e) i n ov er all p ai n as m e as ur e d by t h e V A S, c alc ul at e d as f oll o ws: 
•  
A bs ol ut e c h a n g e ( Δ) at t h e s u bj ect l ev el will b e c alc ul at e d as:  
Δ = V A S F oll o w -u p - V A S B as e  
W h er e V A S B as e  a n d V A S F oll o w -u p ar e t h e v al u e of t h e ov er all V A S p ai n sc or e  at b as eli n e a n d f oll o w -
u p, r es p ectiv ely . A n e g ati v e v al u e i n dic at es a n i m pr ov e m e nt (r e d ucti o n) i n p ai n. 
•  
P erc e nt a g e c h a n g e  at t h e s u bj ect l ev el  will b e c alc ul at e d as 1 0 0 ti m es t h e a bs ol ut e c h a n g e 
divi d e d by t h e b a s eli n e v al u e.  
P erc e nt a g e c h a n g e = 1 0 0 * Δ/ V A S B as e  
1 4. 5. 1. 3  
A n al y si s M et h o d s  
A p oi nt esti m at e of t h e pr o p orti o n of r es p o n d ers, al o n g wit h a 9 5 % c o nfi d e nc e i nt er v al, will b e 
pr es e nt e d f or t h is o bj ectiv e.    
1 4. 5. 1. 4  
D et er mi n ati o n of S u bj e ct s / D at a f or A n al y si s  
I nf or m ati o n fr o m l o w-b ack a n d/ or l e g p ai n  s u bj ects w h o pr ovi d e d at a at b as eli n e a n d t h e 3-M o nt h Visit 
(l o w-b ack a n d/ or l e g p ai n s u bj ects fr o m t h e C C S ) will b e us e d f or t his o bj ectiv e.  
As a s e nsitivity a n alysis, if t h er e is gr e at er t h a n 5 % of s u bj ects wit h missi n g v al u es, a ny s u bj ects w h o 
w er e d e vic e -i m pl a nt e d (F AS ) b ut ar e missi n g t h eir V AS sc or es at t h e 3-M o nt h Visit  will b e i m p ut e d usi n g 
M ulti pl e I m p ut ati o n ( MI). Pri or t o t h e us e of MI, t h e distri b uti o ns of t h e c o nti n u o us v ari a bl es will b e 
a ss ess e d f or n or m ality a n d tr a nsf or m ati o n m a y b e c o nsi d er e d if t h e y ar e n ot n or m all y distri b ut e d. 
 
 
F oll o wi n g i m p ut ati o n, t h e o bj ectiv e will b e e v al u at e d usi n g 
MI a n al ysis m et h o d.  
 
 
 
1 4. 5. 2  
S e c o n d ar y O bj e cti v e 2: P ai n -S p e cifi c R e s p o n d er R at e s 
T his o bj ectiv e is t o c h ar act eriz e t h e effic ac y r es p o n d er r at e wit hi n i n e ac h ty p e of p ai n (l o w -b ac k or l e g) 
f or l o w-b ac k a n d / or l e g p ai n s u bj ects, as m e as ur e d by t h e p ai n -s p ecific V A S, fr o m B as eli n e t o t h e 3-

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 4  of 1 1 7  
 
 
 
 
 
M o nt h Visit.  T h e l o w -b ac k r es p o n d er r at e will b e c h ar act eriz e d f or s u bj ects wit h b as eli n e b ac k V A S ≥ 6 0 
m m , a n d t h e l e g r es p o n d er r at e will b e c h ar act eriz e d f or s u bj ects wit h b as eli n e l e g V A S ≥ 6 0 m m.          
1 4. 5. 2. 1  
H y p ot h e si s  
T h er e is n o hy p ot h esis t est f or t h is o bj ectiv e. T h e p ur p os e is t o c h ar act eriz e t h e p ai n -s p ecific effic ac y 
r es p o n d er r at e at t h e 3-M o nt h  Visit.  
1 4. 5. 2. 2  
E n d p oi nt d efi niti o n a n d d eri v ati o n  
A r es p o n d er will b e a ny l o w-b ac k a n d / or l e g p ai n s u bj ect w h o d e m o nstr at es at l e ast a 5 0 % i m pr o v e m e nt 
( p erc e nt c h a n g e) i n p ai n -s p ecific sc or e as m e as ur e d by t h e V A S , c alc ul at e d as f oll o ws:  
•  
A bs ol ut e c h a n g e ( Δ) at t h e s u bj ect l ev el will b e c alc ul at e d as:  
Δ = V A S F oll o w -u p - V A S B as e  
W h er e V A S B as e  a n d V A S F oll o w -u p ar e t h e v al u e of t h e b ac k or l e g V A S p ai n sc or e  at b as eli n e a n d 
f oll o w-u p, r es p ectiv el y . A n e g ati v e v al u e i n dic at es a n i m pr ov e m e nt (r e d ucti o n) i n p ai n. 
•  
P erc e nt a g e c h a n g e  at t h e s u bj ect l ev el  will b e c alc ul at e d as 1 0 0 ti m es t h e a bs ol ut e c h a n g e 
divi d e d by t h e b as eli n e v al u e.  
P erc e nt a g e c h a n g e = 1 0 0 * Δ / V A S B as e  
1 4. 5. 2. 3  
A n al y si s M et h o d s  
A p oi nt esti m at e of t h e pr o p orti o n of r es p o n d ers, al o n g wit h a 9 5 % c o nfi d e nc e i nt er v al, will b e 
pr es e nt e d f or e ac h p ai n c at e g or y  wit hi n t h e s ec o n d ar y  o bj ecti v e . A d diti o n al r es ults, s uc h as t h e 
pr o p orti o n of r es p o n d ers by p ai n c at e g ory  a n d sit e, m a y b e pr o v i d e d as w ell. 
1 4. 5. 2. 4  
D et er mi n ati o n of S u bj e ct s / D at a f or A n al y si s  
I nf or m ati o n fr o m s u bj ects w h o pr o vi d e d at a at b as eli n e a n d t h e 3-M o nt h  Visit ( C C S ) will b e us e d f or t his 
o bj ectiv e.  F or t h e a n alysis of b ac k p ai n r es p o n d er r at e, t h e s u bs et of C C S  s u bj ects wit h a b as eli n e b ac k 
V A S ≥ 6 0 m m  will b e us e d .  F or t h e a n al ysis of l e g p ai n r es p o n d er r at e, t h e s u bs et of C C S s u bj ects wit h 
b as eli n e l e g  V A S  ≥ 6 0  m m  will b e us e d.  
As a s e nsitivity a n alysis, if t h er e is gr e at er t h a n 5 % of s u bj ects wit h missi n g v al u es, a ny  s u bj ects w h o 
w er e d e vic e -i m pl a nt e d (F AS ) b ut ar e missi n g t h eir V AS sc or es at t h e 3-M o nt h Visit will b e i m p ut e d  usi n g 
M ulti pl e I m p ut ati o n ( MI). Pri or t o t h e us e of MI, t h e distri b uti o ns of t h e c o nti n u o us v ari a bl es will b e 
ass ess e d f or n or m ality a n d tr a nsf or m ati o n m a y b e c o nsi d er e d if t h e y ar e n ot n or m all y distri b ut e d. 
 
 
 
F oll o wi n g i m p ut ati o n, t h e o bj ectiv e will b e ev al u at e d usi n g MI a n al ysis m et h o d.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 5  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
  
 
 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 6  of 1 1 7  
 
 
 
 
 
 
 
1 4. 7  S af et y A s s e s s m e nt  
T o c h ar act eriz e all d evic e -r el at e d, t h er a py-r el at e d, a n d pr oc e d ur e-r el at e d a dv ers e ev e nts a n d d e vic e 
d efici e nci es fr o m t h e st art of t h e d evic e tri al  u ntil st u dy exit. A dv ers e e v e nts a n d d e vic e d efici e nci es will 
b e s u m m ariz e d usi n g s u m m ar y t a bl es dis pl a yi n g t h e fr e q u e nc y a n d p erc e nt a g es  of ev e nts as w ell as t h e 
n u m b er of s u bj ects ex p e ri e nci n g e v e nts, by st u dy p h as e, a n d i n t ot al. A dv ers e ev e nts will b e 
s u m m ariz e d by s eri o us n ess as w ell. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
F or t h e pri m ary o bj ecti v e, a s u bs et  ( 2 8) of t h e t ot al  d e vic e i m pl a nt e d  l o w-b ack a n d / or l e g p ai n s u bj ects 
ar e n e e d e d t o ev al u at e t h e e n d p oi nt . For t h e s ec o n d ar y o bj ectiv es, u p t o 4 5 i m pl a nt e d s u bj ects wit h 
l o w-b ack a n d / or l e g p ai n ar e d esir e d t o c h ar act eriz e t h e r es p o n d er r at es at t h e 3-M o nt h Visit. U p t o 9 
i m pl a nt e d s u bj ects wit h u p p er li m b a n d/ or n ec k p ai n ar e d esir e d t o c h ar act eriz e t h e p o p ul ati o n at t h e 3 -
M o nt h Visit.  
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 7  of 1 1 7  
 
 
 
 
 
 
 
 
1 4. 9  Mi ni mi z ati o n of Bi a s  
S el ecti o n of s u bj ects, tr e at m e nt of s u bj ects, a n d ev al u ati o n of st u dy d at a ar e p ot e nti al s o urc es of bi as. 
M et h o ds i nc or p or at e d i n t h e st u dy d esi g n t o mi ni miz e p ot e nti al bi as i ncl u d e ( b ut ar e n ot li mit e d t o): 
•  
S u bj ects’ i n-cli nic t esti n g s e q u e nc es ar e r a n d o miz e d wit h str atific ati o n at e ac h sit e.  T his is t o 
e ns ur e s u bj ects g et e q u al  o p p ort u niti es t o st art wit h eit h er N e ur o S e ns e O n or Off t esti n g.  
•  
S u bj ects ar e bli n d e d t o t h e N e ur o S e ns e O n  or N e ur o S e ns e Off  t esti n g s etti n gs. T his is t o e ns ur e 
t h at t h e k n o wl e d g e of t esti n g s etti n gs is n ot g oi n g t o i nfl u e nc e t h e s u bj ects’ ass ess m e nt of 
o v ersti m ul ati o n s e ns ati o n.  
•  
Missi n g  d at a ar e a p ot e nti al s o urc e of bi as w h e n a n al yzi n g st u dy d at a. A ri g or o us st u dy d esi g n 
a n d ex ec uti o n will h el p pr ev e nt t h e i nci d e nc e of missi n g d at a fr o m occ urri n g. All eff orts will b e 
m a d e t o e ns ur e p ati e nt visits  ar e c o m pl et e d wit h li mit e d attriti o n t o e ns ur e i nt er pr et a bilit y of 
st u dy r es ults. 
•  
T o r e d uc e t h e p ossi bilit y of at y pic al r es ults fr o m a sit e o v erl y i nfl u e nci n g t h e c o m bi n e d r es ults, 
t h e m axi m u m n u m b er of s u bj ects t o b e e nr oll e d at a si n gl e st u dy sit e is li mit e d t o 1 8 a n d c a n n ot 
b e i ncr e as e d wit h o ut pri or s p o ns or a p pr ov al. 
•  
A st atistic al a n al ysis pl a n will b e d e v el o p e d pri or t o a n al yzi n g d at a w hic h will d oc u m e nt all 
pr es p ecifi e d a n alys es a n d a n al ysis m et h o ds . 
•  
All st u dy i nv esti g at ors will b e tr ai n e d o n a n d r e q uir e d t o f oll o w t h e CI P . 
•  
A ll st u dy i nv esti g at ors a n d M e dtr o nic p ers o n n el will b e tr ai n e d o n t h eir r es p ectiv e as p ects of 
t h e st u dy usi n g st a n d ar diz e d tr ai ni n g m at eri als. 
•  
All sit es will us e t h e s a m e v ersi o n of t h e CI P a n d st a n d ar diz e d c as e r e p ort f or ms . 
•  
M o nit ori n g will b e c o n d uct e d t o v erif y a d h er e nc e t o t h e CI P . 
I n s u m m ar y, p ot e nti al s o urc es of bi as t h at m a y b e e nc o u nt er e d i n t his st u dy h av e b e e n c o nsi d er e d a n d 
mi ni miz e d by c ar ef ul st u dy d esi g n.  
1 5.  Et hi c s  
1 5. 1  St at e m e nt ( s ) of C o m pli a n c e  
T his st u dy will b e c o n d uct e d i n c o m pli a nc e wit h i nt er n ati o n al et hic al a n d sci e ntific q u alit y st a n d ar ds, 
k n o w n as G C P. G C P i ncl u d es r e vi e w a n d a p pr ov al by a n i n d e p e n d e nt E C b ef or e i niti ati n g a st u dy, 
c o nti n ui n g r evi e w of a n o n g oi n g st u dy by a n E C, a n d o bt ai ni n g a n d d oc u m e nti n g t h e fr e el y giv e n 
i nf or m e d co ns e nt of a s u bj ect b ef or e i niti ati n g t h e st u dy.  
T h e Cl os e d -L o o p S C S st u dy w as d esi g n e d t o r efl ect t h e G C P pri nci pl es o utli n e d i n IS O 1 4 1 5 5: 2 0 2 0 a n d 
ot h er i nt er n ati o n al cli nic al r e q uir e m e nts o utli n e d b el o w.  T h es e i ncl u d e t h e pr ot ecti o n of t h e ri g hts, 
s af et y a n d w ell-b ei n g of h u m a n s u bj ects, c o ntr ols t o e ns ur e t h e sci e ntific c o n d uct a n d cr e di bility of t h e 
cli nic al i nv esti g ati o n a n d t h e d efi niti o n of r es p o nsi biliti es of t h e s p o ns or a n d i nv esti g at ors.  I n 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 8  of 1 1 7  
 
 
 
 
 
acc or d a nc e wit h I S O 1 4 1 5 5: 2 0 2 0, t h e s p o ns or s h all a v oi d i m pr o p er i nfl u e nc e o n, or i n d uc e m e nt of, t h e 
s u bj ect, m o nit or, a ny i nv esti g at or(s) or ot h er p arti es p artici p ati n g i n, or c o ntri b uti n g t o, t h e cli nic al 
i nv esti g ati o n.  All Inv esti g at ors s h all av oi d i m pr o p er i nfl u e nc e o n or i n d uc e m e nt of t h e s u bj ect, s p o ns or, 
m o nit or, ot h er i nv esti g at or(s) or ot h er p arti es p artici p ati n g i n or c o ntri b uti n g t o t h e cli nic al 
i nv esti g ati o n.  A dv ers e Ev e nt a n d D evic e D efici e nc y h a n dli n g is I S O 1 4 1 5 5: 2 0 2 0  c o m pli a nt f or all wit h 
t h e exc e pti o n t h at o nly t h os e A Es t h at ar e d evic e r elat e d, pr oc e d ur e r el at e d, t h er a py r el at e d or s eri o us, 
will b e c oll ect e d.  N o n -s u bj ect A Es will n ot b e c oll ect e d. O nl y  t h e m ost r el e v a nt A Es  t o t h e st u dy d e vic e 
a n d st u dy d esi g n ar e b ei n g c oll ect e d b ec a us e n o n e w or i ncr e as e d risk  w er e i d e ntifi e d f or t h e s u bj ect or 
p ers o n h a n dli n g t h e I nc e ptiv syst e m. 
S u bj ects will r ec ei v e t h e st u dy d e vic e fr e e of c h ar g e a n d a m o d est a m o u nt of m o n e y t o r ei m b urs e f or 
tr av el t o r e q uir e d visits.  
M e dtr o nic c o ntr acts wit h p artici p ati n g i nstit uti o ns/i nv esti g at ors t hr o u g h a cli nic al tri al a gr e e m e nt t h at 
d efi n es t h e sc o p e a n d r es p o nsi biliti es a n d ass oci at e d c o m p e ns ati o n r el at e d t o c arr yi n g o ut t h e  
o bli g ati o ns u n d er a cli nic al st u dy s p o ns or e d by M e dtr o nic.  
 
T h e pri nci pl es of t h e D ecl ar ati o n of H elsi nki (D o H ) h a v e b e e n i m pl e m e nt e d t hr o u g h t h e I C pr oc ess, E C 
a p pr o v al, st u dy tr ai ni n g, cli nic al tri al r e gistr ati o n, pr e -cli nic al t esti n g, ris k-b e n efit ass ess m e nt a n d 
p u blic ati o n p olicy.  
Ulti m at el y, all st u dy sit es will f oll o w a n d c o m pl y wit h:  
•  
Pri nci pl es of D o H  
•  
I S O 14 1 5 5: 2 0 2 0  
•  
2 1 C F R P art 1 1 ( El ectr o nic R ec or ds, El ectr o nic Si g n at ur es)  
•  
T h e Cli nic al Tri al A gr e e m e nt  
•  
T h e pr oc e d ur es d escri b e d wit hi n t his CI P  
•  
L oc al E C R e q uir e m e nts 
 
T h e st u dy will b e p u blicl y r e gist er e d i n acc or d a nc e wit h t h e D o H. I n a d diti o n, t h e st u dy m a y b e 
r e gist er e d i n l oc al r e g ul at or y d at a b as es w h er e r e q uir e d by l oc al l a w.  
A p pr o v al of t h e CI P a n d CI P a m e n d m e nts is r e q uir e d fr o m t h e f oll o wi n g gr o u ps pri or t o a ny  st u dy 
pr oc e d ur es at a st u dy sit e:  
•  
M e dtr o nic  
•  
Pri nci p al I nv esti g at ors  
•  
A n i n d e p e n d e nt m e dic al E C  
Si mil arl y, a p pr ov al of s u bs e q u e nt r e visi o ns t o t h e CI P is r e q uir e d at e ac h st u dy sit e fr o m t h e a b o v e 
m e nti o n e d gr o u ps pri or t o i m pl e m e nt ati o n of t h e r evis e d CI P at t h e st u dy sit e. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 7 9  of 1 1 7  
 
 
 
 
 
1 6.  St u d y A d mi ni str ati o n  
1 6. 1  M o nit ori n g  
It is t h e r es p o nsi bilit y of M e dtr o nic t o e ns ur e pr o p er m o nit ori n g of t his st u dy.  Tr ai n e d M e dtr o nic 
p ers o n n el or d el e g at es a p p oi nt e d by M e dtr o nic m a y p erf or m st u dy m o nit ori n g at t h e st u dy sit e i n or d er 
t o e ns ur e t h at t h e st u dy is c o n d uct e d i n acc or d a nc e wit h t h e CI P, t h e C T A, a n d t h e a p plic a bl e r e g ul at ory 
a n d l oc al r e q uir e m e nts. M e dtr o nic, or d el e g at es, m ust t h er ef or e b e all o w e d dir ect acc ess t o t h e 
s u bj ects’ c as e hist ori es (cli nic a n d h os pit al r ec or ds, a n d ot h er s o urc e d at a/ d oc u m e nt ati o n) u p o n r e q u est 
as p er t h e I C F a n d C T A.  T h e pri nci p al i nv esti g at or s h o ul d als o b e a v ail a bl e d uri n g m o nit ori n g visits.   
1 6. 1. 1  
M o nit ori n g Vi sit s  
Fr e q u e nc y of m o nit ori n g visits m a y b e b as e d u p o n s u bj ect e nr oll m e nt, st u dy  c o m pli a nc e, n u m b er of 
a dv ers e ev e nts, n u m b er of d e vi ati o ns, o bs erv ati o ns fr o m pr evi o us m o nit ori n g visits a n d a ny s us p ect e d 
i nc o nsist e nc y i n d at a t h at r e q uir es i nv esti g ati o n. R e g ul at ory d oc u m e nts will b e r evi e w e d at e ac h st u dy 
sit e. M o nit ori n g f or t h e st u d y, i ncl u di n g sit e i niti ati o n visits, i nt eri m m o nit ori n g visits, a n d cl os e o ut visits, 
will b e d o n e i n acc or d a nc e t o t h e st u dy -s p ecific m o nit ori n g pl a n. 
M o nit ori n g visits m ay b e c o n d uct e d p eri o dic ally t o ass ess st u dy sit e pr o gr ess, t h e i nv esti g at or’s 
a d h er e n c e t o t h e CI P, r e g ul at ory c o m pli a nc e i ncl u di n g b ut n ot li mit e d t o E C a p pr ov al a n d r evi e w of t h e 
st u dy, m ai nt e n a nc e of r ec or ds a n d r e p orts, a n d r e vi e w of s o urc e d oc u m e nts a g ai nst s u bj ect C R Fs i n 
acc or d a nc e t o t h e st u dy -s p ecific m o nit ori n g pl a n. M o nit ors r e vi e w st u dy sit e r e g ul at or y a n d st u dy 
c o m pli a nc e by i d e ntifyi n g o bs erv ati o ns of n o n -c o m pli a nc e a n d c o m m u nic ati n g t h os e o bs erv ati o ns al o n g 
wit h r ec o m m e n d ati o ns f or pr e v e nt ati v e/c orr ectiv e acti o ns t o st u dy sit e p ers o n n el.  M o nit ors m a y w or k 
wit h st u dy p ers o n n e l t o d et er mi n e a p pr o pri at e c orr ecti v e acti o n r ec o m m e n d ati o ns a n d t o i d e ntif y 
tr e n ds wit hi n t h e st u dy or at a p artic ul ar st u dy sit e. 
1 6. 2  D at a M a n a g e m e nt  
D at a will b e c oll ect e d usi n g a n el ectr o nic d at a m a n a g e m e nt s yst e m f or st u di es.  C as e R e p ort F or m ( C R F ) 
d at a will b e st or e d i n a s ec ur e, p ass w or d -pr ot ect e d d at a b as e w hic h will b e b ac k e d u p ni g htl y.  D at a will 
b e r evi e w e d usi n g pr o gr a m m e d a n d m a n u al d at a c h ecks.  D at a q u eri es will b e m a d e a v ail a bl e t o st u dy 
sit es f or r es ol uti o n.  St u dy m a n a g e m e nt r e p orts m ay b e g en er at e d t o m o nit or d at a q u alit y a n d st u dy 
pr o gr ess.  At t h e e n d of t h e st u dy, t h e d at a will b e fr oz e n a n d will b e r et ai n e d by M e dtr o nic  i n 
acc or d a nc e wit h  a p plic a bl e  r e g ul ati o ns. 
All r ec or ds a n d ot h er i nf or m ati o n a b o ut s u bj ects p artici p ati n g i n t his st u dy will b e tr e at e d as 
c o nfi d e nti al. D at a will b e tr a nsf err e d a n d pr oc ess e d by M e dtr o nic or a t hir d p arty d esi g n at e d by 
M e dtr o nic i n a k ey c o d e d f or m, u nl ess it’s i m p ossi bl e t o ps e u d o ny miz e f or i nst a nc e, w h er e t h e s u bj ect’s 
n a m e c a n n ot b e r e m ov e d fr o m t h e d at a c arri er, s uc h as di a g n ostic  i m a g es.     
Pr oc e d ur es i n t h e CI P r e q uir e s o urc e d oc u m e nt ati o n. S o urc e d oc u m e nt ati o n will b e m ai nt ai n e d at t h e 
st u dy sit e. S o urc e d oc u m e nts, w hic h m ay i ncl u d e w orks h e ets, s u bj ect m e dic al r ec or ds, pr o gr a m m er 
pri nt o uts, a n d i nt err o g ati o n fil es, m ust b e cr e at e d a n d m ai nt ai n e d by t h e i nv esti g ati o n al st u dy sit e 
t e a m.  
T h e Inv esti g at or will cl e arly m ar k cli nic al r ec or ds t o i n dic at e t h at t h e s u bj ect is e nr oll e d i n t his cli nic al 
i nv esti g ati o n. T h e I nv esti g at or is r es p o nsi bl e f or c o m pl eti o n a n d si g n off of e C R Fs.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 0  of 1 1 7  
 
 
 
 
 
T h e d at a r e p ort e d o n t h e C R Fs s h all b e d eri v e d fr o m s o urc e d oc u m e nts a n d b e c o nsist e nt wit h t h es e 
s o urc e d oc u m e nts, a n d a ny discr e p a nci es s h all b e ex pl ai n e d i n writi n g. S e e S ecti o n 1 0. 3 1  f or C R Fs a n d 
d at a c oll ecti o n el e m e nts t h at m a y b e c o nsi d er e d s o urc e.  
D evic e d at a fr o m tr a ns missi o ns will b e u pl o a d e d t o s ec ur e s erv ers.  D e vic e  d at a c oll ect e d at offic e visits 
will b e s e nt t o M e dtr o nic. U p o n r ec ei pt, d e vic e d at a will b e m ai nt ai n e d wit h d at a b as es a n d r etri ev e d f or 
a n al ysis a n d r e p orti n g.  
1 6. 3  Dir e ct A c c e s s t o S o ur c e D at a / D o c u m e nt s  
M e dtr o nic m ay c o n d uct a u di ts at p artici p ati n g st u dy sit es. T h e p ur p os e of a n a u dit is t o v erify t h e 
p erf or m a nc e of t h e m o nit ori n g pr oc ess a n d t h e st u dy c o n d uct, i n d e p e n d e ntl y of t h e p ers o n n el dir ectl y 
i nv olv e d i n t h e st u dy. Re g ul at ory a g e nci es  m a y als o p erf or m i ns p ecti o ns at p artic i p ati n g st u dy sit es. T h e 
i nv esti g at or a n d/ or i nstit uti o n s h all p er mit M e dtr o nic, E C  a n d R e g ul at ory a g e nci es dir ect acc ess t o 
s o urc e d at a a n d d oc u m e nts d uri n g m o nit ori n g, a u dits a n d r e g ul at ory i ns p ecti o ns.  
1 6. 4  C o nfi d e nti alit y  
All i nf or m ati o n a n d d at a s e nt t o p arti es i nv ol v e d i n st u dy c o n d uct c o nc er ni n g s u bj ects or t h eir 
p artici p ati o n i n t his st u dy will b e c o nsi d er e d c o nfi d e nti al. St u dy sit es will assi g n a u ni q u e S u bj ect I D t o 
e ac h s u bj ect. R ec or ds of t h e s u bj ect  ID r el ati o ns hi p will b e m ai nt ai n e d by t h e st u dy sit e. T h e s u bj ect I D 
n u m b er is t o b e r ec or d e d o n all st u dy d oc u m e nts t o li n k t h e m t o t h e s u bj ect’s m e dic al r ec or ds at t h e 
st u dy sit e.  C o nfi d e nti ality of d at a will b e o bs er v e d by all p arti es i nv ol v e d at all ti m es t hr o u g h o ut t h e 
cli nic al i nv esti g ati o n. All d at a s h all b e s ec ur e d a g ai nst u n a ut h oriz e d acc ess. T h e pri v ac y of e ac h s u bj ect 
a n d c o nfi d e nti ality of his/ h er i nf or m ati o n s h all b e pr es er v e d i n r e p orts a n d w h e n p u blis hi n g a ny d at a.  
T o m ai nt ai n c o nfi d e nti alit y, t h e s u bj ect’s n a m e or a ny ot h er Pr ot ect e d H e alt h I nf or m ati o n  ( P HI) s h o ul d 
n ot b e r ec or d e d o n a ny st u dy d oc u m e nt ot h er t h a n t h e I C F . T his sc e n ari o will b e c o v er e d i n t h e I CF . I n 
t h e ev e nt a s u bj ect’s n a m e/ P HI is i ncl u d e d f or a ny r e as o n, it will b e bli n d e d as a p plic a bl e. I n t h e e v e nt of 
i n a bilit y t o bli n d t h e i d e ntific ati o n ( e. g., di git al m e di a), it will b e h a n dl e d i n a c o nfi d e nti al m a n n er by t h e 
a ut h oriz e d p ers o n n el.  D at a r el ati n g t o t h e st u dy mi g ht b e m a d e av ail a bl e t o t hir d p arti es (f or ex a m pl e 
i n c as e of a n a u dit p erf or m e d by Re g ul at ory A ut h ority ), pr ovi d e d t h e d at a ar e tr e at e d as c o nfi d e nti al 
a n d t h at t h e s u bj ect’s pri v ac y is g u ar a nt e e d. N o i d e ntifi a bl e s u bj ect i nf or m ati o n will b e p u blis h e d.  
1 6. 5  Li a bilit y  
1 6. 5. 1  
I n s ur a n c e ( A u str ali a )  
M e dtr o nic A ustr al asi a Pt y Lt d is a w h olly o w n e d s u bsi di ar y of M e dtr o nic, w hic h as t h e p ar e nt c o m p a ny 
of s uc h e ntity m ai nt ai ns a p pr o pri at e cli nic al st u dy li a bilit y i ns ur a nc e c ov er a g e as r e q uir e d u n d er 
a p plic a bl e l a ws a n d r e g ul ati o ns a n d will c o m pl y wit h a p plic a bl e l oc al l a w a n d c ust o m c o nc er ni n g s p ecific 
i ns ur a nc e c o ver a g e. If r e q uir e d, a Cli nic al St u dy i ns ur a nc e st at e m e nt/c ertific at e will b e pr o vi d e d t o t h e 
E C.  
1 6. 6  C I P A m e n d m e nt s  
A ny r evisi o ns or a m e n d m e nts t o t h e CI P or I C d oc u m e nt, al o n g wit h a st at e m e nt of j ustific ati o n f or t h e 
c h a n g es, will b e s u b mitt e d t o all aff ect e d R As a n d g ov er ni n g E Cs, acc or di n g t o a p plic a bl e r e g ul ati o ns.    
A p pr o v al by E Cs m ust b e o bt ai n e d pri or t o i m pl e m e nti n g a CI P r e visi o n at t h e st u dy sit e.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 1  of 1 1 7  
 
 
 
 
 
1 6. 7  R e c or d R et e nti o n  
All st u dy -r el at e d d oc u m e nts (i ncl u di n g a p plic a bl e S o urc e D oc u m e nts, C R Fs, I nv esti g at or Sit e Fil e, 
el ectr o nic d at a etc.) m ust b e r et ai n e d f or a p eri o d of at l e ast 2 y e ars aft er m ar k et -r el e as e i n his/ h er 
r e gi o n a n d aft er st u dy cl os ur e ( or l o n g er if r e q uir e d by l oc al l a w).   
N o st u dy d oc u m e nt or i m a g e will b e d estr o y e d wit h o ut pri or writt e n a g r e e m e nt b et w e e n M e dtr o nic 
a n d t h e Inv esti g at or. T h e Inv esti g at or s h o ul d t ak e m e as ur es t o pr ev e nt acci d e nt al or pr e m at ur e 
d estr ucti o n of d oc u m e nts.  S h o ul d t h e Inv esti g at or wis h t o assi g n t h e st u dy r ec or ds t o a n ot h er p arty or 
m ov e t h e m t o a n ot h er l oc ati o n, a dv a nc e writt e n n otic e m ust b e giv e n t o M e dtr o nic.  
M e dtr o nic will r et ai n t h e st u dy r ec or ds acc or di n g t o M e dtr o nic c or p or at e p olic y a n d r ec or d r et e nti o n 
sc h e d ul e. 
1 6. 7. 1  
I n v e sti g at or R e c or d s  
T h e Inv esti g at or is r es p o nsi bl e f or t h e pr e p ar ati o n a n d r et e nti o n of t h e r ec or ds cit e d b el o w.  All of t h e 
b el o w r ec or ds, wit h t h e exc e pti o n of c as e hist ory r ec or ds a n d c as e r e p ort f or ms, s h o ul d b e k e pt i n t h e 
I nv esti g at or Sit e Fil e (i. e., t h e st u dy bi n d er pr ovid e d t o t h e i nv esti g at or) or S u bj ect St u dy Bi n d er. C R Fs 
m ust b e m ai nt ai n e d a n d si g n e d el ectr o nic ally wit hi n t h e el ectr o nic d at a c a pt ur e s yst e m d uri n g t h e 
st u dy. T h e f oll o wi n g r ec or ds ar e s u bj ect t o i ns p ecti o n a n d m ust b e r et ai n e d f or a p eri o d of 1 5  y e ars ( o r 
l o n g er as l oc al l a w or h os pit al a d mi nistr ati o n r e q uir es) aft er pr o d uct a p pr o v al or t h e d at e o n w hic h t h e 
i nv esti g ati o n is t er mi n at e d or t h e d at e t h at t h e r ec or ds ar e n o l o n g er r e q uir e d f or p ur p os es of 
s u p p orti n g a pr e-m ar k et a p pr o v al a p plic ati o n.  
•  
All c or r es p o n d e nc e b et w e e n t h e E C, s p o ns or, m o nit or, R e g ul at or y A ut h ority  a n d t h e 
Inv esti g at or t h at p ert ai ns t o t h e Inv esti g ati o n, i ncl u di n g r e q uir e d r e p orts.  
•  
S u bj ect’s c as e hist ory r ec or ds, i ncl u di n g:  
 
Si g n e d a n d d at e d I C by s u bj ect a n d Inv esti g at or  
 
O bs er v ati o n s of A Es/ D Ds 
 
M e dic al hist ory  
 
Tri al, I m pl a nt, T esti n g a n d visit  d at a  
 
D oc u m e nt ati o n of t h e d at es a n d r ati o n al e f or a ny d evi ati o n fr o m t h e pr ot oc ol  
•  
List of i nv esti g ati o n st u dy sit es 
•  
Fi n a nci al Discl os ur e   
•  
S u bj ect scr e e ni n g l o g & I D l o g (if a p plic a bl e)  
•  
N or m al v al u e(s)/r a n g e(s) f or cli nic al l a b or at ory t est (if a p plic a bl e)  
•  
L a b c ertific at e (if a p plic a bl e) 
•  
D evic e Dis p ositi o n L o gs c o nt ai ni n g M o d el a n d s eri al n u m b ers of d evic es d eliv er e d t o t h e  
st u dy sit e, s u bj ect I Ds of t h e s u bj ects i m pl a nt e d, r ec eiv e d d at es of d evic es, i m pl a nt/ us e d 
d at es, ex pl a nt d at es, r et ur n e d -t o-s p o ns or d at es a n d r e as o ns, all p ers o ns w h o r ec ei v e d, 
us e d or dis p os e d e ac h d e vic e, a n d m et h o d of dis p os al/ d estr ucti o n.  
•  
N o n i m pl a nt a bl e d evic e Dis p ositi o n L o gs c o nt ai ni n g M o d el a n d s eri al/l ot n u m b ers, 
s u bj ect I Ds of t h e s u bj ects r ec eivi n g d e vic e, r ec eiv e a n d r et ur n d at e by p ati e nt, 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 2  of 1 1 7  
 
 
 
 
 
r et ur n e d-t o-s p o ns or d at es, dis p os al / d estr ucti o n d at e, all p ers o ns w h o r ec eiv e d d e vic e 
fr o m sp o ns or or s u bj ect, r et ur n e d or dis p os e d/ d estr uct d e vic e, a n d r e as o n a n d m et h o d 
of dis p os al/ d estr ucti o n.  
•  
All a p pr o v e d v ersi o ns of t h e CI P, I C, I nv esti g at or B r oc h ur e  
•  
Si g n e d a n d d at e d C T A  
•  
C V si g n e d a n d d at e d of P ri nci p al Inv esti g at ors a n d k ey m e m b ers of i nv esti g ati o n st u dy 
sit e t e a m ( as r e q uir e d by a p plic a bl e r e g ul ati o ns 
•  
D oc u m e nt ati o n of d el e g at e d t as ks  
•  
E C a p pr ov al d oc u m e nt ati o n. Writt e n i nf or m ati o n t h at t h e i nv esti g at or or ot h er st u dy 
st aff, w h e n m e m b er of t h e E C, di d n ot p artici p at e i n t h e a p pr ov al pr oc ess. A p pr ov al 
d oc u m e nt ati o n m ust i ncl u d e t h e E Cs c o m p ositi o n, w h er e r e q uir e d p er l oc al l a w.   
•  
R e g ul at ory A ut h orit y  n otific ati o n, c orr es p o n d e nc e a n d a p pr o v al, w h er e r e q uir e d p er 
l oc al l a w. 
•  
St u dy tr ai ni n g r ec or ds f or st u dy sit e st aff  
•  
I ns ur a nc e c ertific at es  
•  
S hi p pi n g r ec or ds of i nv esti g ati o n al d evic es  
•  
E q ui p m e nt m ai nt e n a nc e r ec or ds, if a p plic a bl e  
•  
A ny ot h er r ec or ds t h at l oc al r e g ul at ory a g e nci es r e q uir e t o b e m ai nt ai n e d  
•  
Fi n al St u dy R e p ort i ncl u di n g t h e st atistic al a n al ysis  
1 6. 7. 2  
S p o n s or R e c or d s  
M e dtr o nic s h all m ai nt ai n t h e f oll o wi n g acc ur at e, c o m pl et e, a n d c urr e nt r ec or ds:  
•  
All c orr es p o n d e nc e w hic h p ert ai ns t o t h e i nv esti g ati o n  
•  
I nv esti g ati o n al d evic e tr ac e a bilit y r ec or d c o nt ai ni n g M o d el a n d s eri al n u m b ers of 
d e vic es, s hi p pi n g d at e a n d n a m e a n d a d dr ess of p ers o n t h at r ec ei v e d s hi p p e d d evic e, 
l oc ati o n (if diff er e nt t h a n p ers o n s hi p p e d t o), tr a nsf er a n d r ec ei pt by M e dtr o nic d at es. 
•  
N o n i m pl a nt a bl e d evic e tr ac e a bilit y r ec or ds c o nt ai ni n g M o d el a n d s eri al/l ot n u m b ers, 
s hi p pi n g d at e a n d n a m e a n d a d dr ess of p ers o n t h at r ec ei v e d s hi p p e d d evic e, l oc ati o n (if 
diff er e nt t h a n p ers o n s hi p p e d t o), tr a nsf er a n d r ec ei pt by M e dtr o nic d at es.  
•  
S a m pl e of l a b el att ac h e d t o i nv esti g ati o n al d e vic e  
•  
Si g n e d I nv esti g at or Tri al A gr e e m e nts, Fi n a nci al Discl os ur e a n d c urr e nt si g n e d a n d d at e d 
C V of P ri nci p al Inv esti g at or a n d k ey m e m b ers of t h e i nv esti g ati o n st u dy sit e t e a m ( as 
r e q uir e d by l oc al l a w), d el e g at e d t ask list 
•  
All a p pr o v e d I C t e m pl at es, a n d ot h er i nf or m ati o n pr ovi d e d t o t h e s u bj ects a n d 
a dv ertis e m e nts, i ncl u di n g tr a nsl ati o ns  
•  
R a n d o miz ati o n r ec or ds  
•  
C o pi es of all E C a p pr o v al l ett ers a n d r el ev a nt E C c orr es p o n d e nc e a n d E C v oti n g 
list/r ost er/l ett er of ass ur a nc e 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 3  of 1 1 7  
 
 
 
 
 
•  
N a m es of t h e i nstit uti o ns i n w hic h t h e st u dy will b e c o n d uct e d  
•  
R e g ul at ory A ut h orit y  c orr es p o n d e nc e, n otific ati o n a n d a p pr o v al as r e q uir e d by n ati o n al 
l e gisl ati o n 
•  
I ns ur a nc e c ertific at es  
•  
N a m es/c o nt act a d dr ess es of m o nit ors  
•  
M o nit ori n g visit r e p orts  
•  
C as e R e p ort F or ms  
•  
St atistic al a n al ys es a n d u n d erl yi n g s u p p orti n g d at a  
•  
Fi n al r e p ort of t h e st u dy  
•  
T h e CI P, I nv esti g at or ’s Br oc h ur e  s u m m ary a n d st u dy r el at e d r e p orts, a n d r evisi o ns 
•  
St u dy tr ai ni n g r ec or ds f or st u dy sit e p ers o n n el a n d M e dtr o nic p ers o n n el i nv ol v e d i n t h e 
st u dy 
•  
A ny ot h er r ec or ds t h at l oc al r e g ul at ory a g e nci es r e q uir e t o b e m ai nt ai n e d  
 
M e dtr o nic r ec or ds a n d r e p orts will b e  m ai nt ai n e d i n a p ass w or d -pr ot ect e d d oc u m e nt m a n a g e m e nt 
s yst e m, a n d p a p er d oc u m e nts ( w h er e a p plic a bl e) will b e st or e d i n st or e d i n s ec ur e d fil e c a bi n ets at 
M e dtr o nic d uri n g t h e c o urs e of t his st u dy.  
Aft er cl os ur e of t h e st u dy M e dtr o nic will r et ai n r ec or ds a n d r e p orts p er M e dtr o nic st a n d ar ds a n d 
a p plic a bl e r e g ul ati o ns . 
1 6. 8  R e p orti n g R e q uir e m e nt s  
1 6. 8. 1  
I n v e sti g at or R e p ort s  
T h e i nv esti g at or is r es p o nsi bl e f or t h e pr e p ar ati o n (r evi e w a n d si g n at ur e) a n d s u b missi o n t o t h e S p o ns or 
of all C R Fs , A Es  a n d a dv ers e d e vic e eff ect s (r e p ort e d p er t h e c o u ntry-s p ecific c oll ecti o n r e q uir e m e nts), 
d e vic e d efici e nci es, d e at hs, a n d a ny d evi ati o ns fr o m t h e CI P .  If a ny acti o n is t a k e n by a n E C wit h r es p ect 
t o t his st u dy, c o pi es of all p erti n e nt d oc u m e nt ati o n m ust b e f or w ar d e d t o M e dtr o nic in a ti m el y 
m a n n er. R e p orts ar e s u bj ect t o i ns p ecti o n a n d t o t h e r et e nti o n r e q uir e m e nts as d escri b e d a b o v e f or 
i nv esti g at or r ec or ds.  
S af et y d at a i nv esti g at or r e p orti n g r e q uir e m e nts ar e list e d i n S ecti o n  1 2 . T h e i nv esti g at or s h all pr e p ar e 
a n d s u b mit i n a c o m pl et e, acc ur at e a n d ti m el y m a n n er t h e r e p orts list e d i n t his s ecti o n.  
T a bl e 1 1 : I n v esti g at or r e p orts a p plic a bl e f or all g e o gr a p hi es p er M e dtr o nic r e q uir e m e nts 
R e p ort  
S u b mit t o  
D escri pti o n/ C o nstr ai nts  
Wit h dr a w al of I R B/ E C 
a p pr o v al  
S p o ns or  a n d 
R el ev a nt 
A ut h oriti es, w h er e 
a p plic a bl e p er 
l oc al r e q uir e m e nts 
R e p ort if r e q uir e d by l oc al l a w.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 4  of 1 1 7  
 
 
 
 
 
R e p ort  
S u b mit t o  
D escri pti o n/ C o nstr ai nts  
Pr o gr ess R e p ort  
S p o ns or a n d  
E C  
Pr ovi d e if r e q uir e d by l oc al l a w or E C.  
St u dy D e vi ati o ns  
S p o ns or  a n d  
E C  
A ny d e vi ati o n fr o m t h e CI P s h all b e r ec or d e d t o g et h er wit h a n 
ex pl a n ati o n f or t h e d e vi ati o n.  D e vi ati o ns s h all b e r e p ort e d t o t h e 
s p o ns or w h o is r es p o nsi bl e f or a n alyzi n g t h e m a n d ass essi n g t h eir 
si g nific a nc e.   
N ot e: W h e n r el ev a nt, et hics c o m mitt e es  or t h e a p pr o pri at e 
R e g ul at ory A ut h orit y  s h o ul d b e i nf or m e d. (I S O 1 4 1 5 5: 2 0 2 0) 
I n t h e ev e nt t h e d e vi ati o n i nv olv es a f ail ur e t o o bt ai n a s u bj ect’s 
c o ns e nt, or is m a d e t o pr ot ect t h e lif e o r p hysic al w ell-b ei n g of a 
s u bj ect i n a n e m er g e ncy, t h e d e vi ati o n m ust b e r e p ort e d t o t h e E C as 
w ell as M e dtr o nic wit hi n fiv e ( 5) w or ki n g d a ys  
 
A ustr ali a: R e p ort a ny s us p ect e d br e ac h es t o t h e s p o ns or a n d 
c o nfir m e d s eri o us br e ac h es t o t h eir i nstit uti o n (r es e arc h g o v er n a nc e 
offic e) wit hi n 7 2 h o urs of b ec o mi n g a w ar e or n otifi e d of t h e s a m e; 
pr o vi d e a ny f oll o w -u p i nf or m ati o n as r e q uir e d a n d w or k wit h t h e 
i nstit uti o n or s p o ns or, as a p pr o pri at e, t o i m pl e m e nt a ny c orr ecti v e 
a n d pr e v e nt ati v e acti o ns  
A ustr ali a - S eri o us Br e ac h:  A br e ac h of G o o d Cli nic al Pr actic e or t h e  
pr ot oc ol t h at is li k ely t o aff ect t o a si g nific a nt d e gr e e:  
a) T h e s af ety or ri g hts of a tri al p artici p a nt, or  
b) T h e r eli a bilit y a n d r o b ust n ess of t h e d at a g e n er at e d i n t h e cli nic al 
tri al. 
N ot e: t his g ui d a nc e's d efi niti o n of s eri o us br e ac h diff ers fr o m t h e 
d efi niti o n i n t h e A ustr ali a n C o d e f or t h e R es p o nsi bl e C o n d uct of 
R es e arc h a n d is a b o ut d evi ati o ns fr o m t h e r e q uir e m e nts of G o o d 
Cli nic al Pr actic e or t h e cli nic al tri als pr ot oc ol.  
( N H M RC R e p orti n g of S eri o us Br e ac h es of G o o d Cli nic al Pr actic e 
( G C P) or t h e Pr ot oc ol f or Tri als I nv olvi n g T h er a p e utic G o o ds 2 0 1 8) 
Fi n al R e p ort  
E Cs a n d r el e v a nt 
a ut h oriti es  
T his r e p ort m ust b e s u b mitt e d as p er l oc al r e q uir e m e nts.  
 
 
1 6. 8. 2  
S p o n s or R e p ort s  
M e dtr o nic s h all pr e p ar e a n d s u b mit t h e f oll o wi n g c o m pl et e, acc ur at e, a n d ti m ely r e p orts list e d i n t h e 
t a bl es b el o w.  I n a d diti o n t o t h e r e p orts list e d b el o w, M e dtr o nic s h all, u p o n r e q u est of t h e r evi e wi n g E C 
or R e g ul at ory A ut h orit y  pr o vi d e acc ur at e, c o m pl e t e a n d c urr e nt i nf or m ati o n a b o ut a ny as p ect of t h e 
i nv esti g ati o n. S af et y d at a M e dtr o nic r e p orti n g r e q uir e m e nts ar e list e d i n S ecti o n 1 2 . 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 5  of 1 1 7  
 
 
 
 
 
T a bl e 1 2 : S p o n s or r e p ort s f or A u str ali a  
R e p ort  
S u b mit t o  
D escri pti o n/ C o nstr ai nts  
Pr e m at ur e 
t er mi n ati o n or 
s us p e nsi o n of t h e 
cli nic al i nv esti g ati o n 
I nv esti g at ors, E C, 
a n d r el e v a nt 
a ut h oriti es  
Pr ovi d e pr o m pt n otific ati o n of t er mi n ati o n or s us p e nsi o n a n d 
r e as o n(s). (I S O 1 4 1 5 5: 2 0 2 0) 
R ec all a n d d evic e 
dis p ositi o n  
I nv esti g at ors, 
E C,  
r el e v a nt 
a ut h oriti es  
N otific ati o n  as p er l oc al r e q uir e m e nts .   
St u dy d e vi ati o n  
I nv esti g at ors 
E ns ur e t h at all d evi ati o ns fr o m t h e CI P ar e r e vi e w e d wit h t h e 
a p pr o pri at e cli nic al i nv esti g at or(s), ar e r e p ort e d o n t h e C R Fs 
a n d t h e fi n al r e p ort of t h e cli nic al i nv esti g ati o n.  (I S O 
1 4 1 5 5: 2 0 2 0)  
S t u dy sit e s p ecific st u dy d eviati o ns will b e s u b mitt e d t o 
i nv esti g at ors p eri o dic all y.   
 
 
R e p ort s eri o us br e ac h es t o t h e r evi e wi n g E C a n d PI wit hi n 7 
c al e n d ar d a ys of c o nfir mi n g a s eri o us br e ac h h as occ urr e d 
a n d pr o vi d e f oll o w -u p w h e n r e q uir e d. ( N H M R C R e p orti n g of 
S eri o us Br e ac h es of G o o d Cli nic al Pr actic e ( G C P) or t h e 
Pr ot oc ol f or Tri als I nv olvi n g T h er a p e utic G o o ds  2 0 1 8)  
Wit h dr a w al of 
a p pr o v al by T G A or 
E C  or a p pr ovi n g 
a ut h ority  
T G A, E C  
N otif y T G A of wit h dr a w al of et hics a p pr o v al.  
 
I n c as e of r e v oc ati o n of C T N or C T X a p p r o v al st at us by T G A, 
s p o ns or t o n otif y E C a n d sit es.  
 
I n c as e of wit h dr a w al of a ut h oriz ati o n fr o m a p pr o vi n g 
a ut h ority, c o m m u nic at e i nf or m ati o n t o t h e E C a n d t o T G A 
 
( A ustr ali a n Cli nic al Tri al H a n d b o o k, v ersi o n 2.4 , A u g 2 0 2 1)  
C o m pl eti o n of cli nic al 
tri al 
T G A 
N otif y T G A of t h e c o m pl eti o n of a cli nic al tri al aft er t h e tri al 
h as b e e n c o m pl et e d at all sit es  al o n g wit h t h e r e as o n t h e 
cli nic al tri al c e as e d (e. g.  c o ncl u d e d n or m all y, i ns uffici e nt 
r ecr uits, etc.) ( A ustr ali a n Cli nic al Tri al H a n d b o o k, v ersi o n 2. 4, 
A u g 2 0 2 1 ) 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 6  of 1 1 7  
 
 
 
 
 
R e p ort  
S u b mit t o  
D escri pti o n/ C o nstr ai nts  
A n n u al s af et y r e p orts, 
si n gl e c as e a dv ers e 
e v e nts, cli nic al st u dy 
r e p ort 
T G A 
S u b mit u p o n r e q u est fr o m T G A  ( A ustr ali a n Cli nic al Tri al 
H a n d b o o k, v ersi o n 2. 4) 
U S A D Es f or A ustr ali a 
a n d i nt er n ati o n al / 
s af et y r e p ort / 
u p d at e d I B / 
a p pr o v e d pr o d uct 
i nf or m ati o n  
I nv esti g at or a n d 
E C  
P er E C r e q uir e m e nts, b ut at l e ast a n n u all y:  
•  
A n n u al s af et y r e p ort i ncl u di n g: a s u m m ary of t h e 
e v ol vi n g s af ety pr ofil e of t h e tri al, a bri ef d escri pti o n 
a n d a n al ysis of n e w/r el ev a nt fi n di n gs, i m plic ati o ns of 
s af et y d at a t o t h e risk-b e n efit r ati o f or t h e tri al, a 
d escri pti o n of a ny m e as ur es t a k e n or pr o p os e d t o 
mi ni miz e ris k s ( N H M R C S af et y m o nit ori n g a n d 
r e p orti n g i n cli nic al tri als i nv olvi n g t h er a p e utic g o o ds, 
N o v e m b er  2 0 1 6, s ecti o n C. 1.i)  
•  
A n u p d at e d/ a d d e n d a of I B or I F U, if a p pr o pri at e ( e. g.  
w h e n a n I B is n o l o n g er m ai nt ai n e d) ( N H M R C S af ety 
m o nit ori n g a n d r e p orti n g i n cli nic al tri als i nv olvi n g 
t h er a p e utic g o o ds, N ov e m b er 2 0 1 6, s ecti o n C. 1. h) 
A cti o n wit h r es p ect t o 
s af et y t h at h as b e e n 
t a k e n by a n ot h er 
c o u ntr y’s r e g ul at ory 
a g e nc y (r el ev a nt t o 
a n o n g oi n g cli nic al 
tri al i n A ustr ali a)   
T G A 
Wit h o ut u n d u e d el a y a n d n o l at er t h a n 7 2 h o urs of t h e tri al 
s p o ns or b ec o mi n g a w ar e of t h e acti o n ( A ustr ali a n Cli nic al 
Tri al H a n d b o ok, v ersi o n 2. 4) 
 
1 6. 9  P u bli c ati o n a n d U s e of I nf or m ati o n  
P u blic ati o ns fr o m t h e Cl os e d -L o o p S C S st u dy will b e h a n dl e d acc or di n g t o St a n d ar d O p er ati n g 
Pr oc e d ur es a n d as i n dic at e d i n t h e C T A.  
1 6. 9. 1  
P u bli c ati o n C o m mitt e e  
M e dtr o nic m ay f or m t h e Cl os e d -L o o p S C S st u dy P u blic ati o n C o m mitt e e fr o m st u dy Inv esti g at ors  a n d 
A dvis ors .  M e dtr o nic p ers o n n el m ay s er v e as m e m b ers of t h e c o m mitt e e.  T his c o m mitt e e will m a n a g e 
st u dy p u blic ati o ns wit h t h e g o al of p u blis hi n g fi n di n gs fr o m t h e d at a.  T h e P u blic ati o n C o m mitt e e will 
d e v el o p t h e fi n al P u blic ati o n Pl a n as a s e p ar at e d oc u m e nt.   
T h e P u blic ati o n C o m mitt e e’s r ol e is t o: 1) m a n a g e el e m e nts a d dr ess e d i n t h e p u blic ati o n pl a n as 
o utli n e d h er e , 2) d ev el o p t h e fi n al P u blic ati o n Pl a n u n d er s e p ar at e c ov er, 3) ex ec ut e t h e P u blic ati o n 
Pl a n, 4) o v ers e e t h e p u blic ati o n of pri m ar y, s ec o n d ary a n d a ncill ar y st u dy r es ults, 5) r evi e w a n d 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 7  of 1 1 7  
 
 
 
 
 
pri oritiz e p u blic ati o n pr o p os als, 6) pr ovi d e i n p ut o n p u blic ati o n c o nt e nt, a n d 7) d et er mi n e a ut h ors hi p.  
I n a d diti o n, t h e c o m mitt e e will a p pl y a n d r ei nf orc e t h e a ut h ors hi p g ui d eli n es s et f ort h i n t h e P u blic ati o n 
Pl a n.   
M e m b ers hi p i n t h e P u blic ati o n C o m mitt e e  d o es n ot g u ar a nt e e a ut h ors hi p.  T h e c o m mitt e e will m e et at 
as n e e d e d.  
1 6. 9. 2  
M a n a g e m e nt of Pri m ar y, S e c o n d ar y, a n d A n cill ar y P u bli c ati o n s  
T h e P u blic ati o n C o m mitt e e r e vi e ws, pri oritiz es, a n d m a n a g es all p u blic ati o ns i ncl u di n g pri m ar y, 
s ec o n d ary a n d a ncill ary p u blic ati o ns.  Pri m ar y a n d s ec o n d ar y p u blic ati o ns ar e t h os e t h at a d dr ess 
a n al ys es of a ny or all pri m ar y o bj ectiv es or s ec o n d ar y o bj ectiv es, r es p ectiv ely, as s p ecifi e d i n t h e CI P.  
A n a ncill ar y p u blic ati o n is a ny p u blic ati o n t h at d o es n ot a d dr ess t h e st u dy o bj e ctiv es i d e ntifi e d i n t h e 
CI P.  T h e y i ncl u d e p u blic ati o ns pr o p os e d a n d d e v el o p e d by ot h er M e dtr o nic d e p art m e nts or e ntiti es, 
cli nici a ns p artici p ati n g i n t his st u dy, a n d cli nici a ns n ot p artici p ati n g i n t his st u dy.  T h e c o m mitt e e will 
w or k wit h M e dtr o nic t o e ns ur e t h at r e q u ests d o n ot pr es e nt c o nflicts wit h ot h er pr o p os als, ar e n ot 
d u plic ativ e, a n d t o d et er mi n e w hic h a ncill ary p u blic ati o n pr o p os als, if a ny, will b e s u p p ort e d.   
T h e c o m mitt e e m a y d eci d e t h at n o p u blic ati o ns, i ncl u di n g a bstr acts, will b e p u blis h e d pri or t o t h e e n d of 
t h e st u dy or wit h i n divi d u al st u dy sit e d at a.  R e q u ests f or p u blic ati o ns o n st u dy o bj ectiv es utilizi n g 
s u bs et d at a ( e. g., r e gi o n al) will b e e v al u at e d f or sci e ntific v ali dity a n d t h e a bilit y of M e dtr o nic t o pr ovi d e 
r es o urc es.   
1 6. 9. 3  
Crit er i a f or D et er mi ni n g A ut h or s hi p 
P u blic ati o ns will a d h er e t o a ut h ors hi p crit eri a d efi n e d by t h e I nt er n ati o n al C o m mitt e e of M e dic al 
J o ur n al E dit ors (I C MJ E, U nif or m r e q uir e m e nts f or m a n uscri pts s u b mitt e d t o bi o m e dic al j o ur n als, 
w w w.ic mj e. or g).  I n di vi d u al a ut h o rs hi p crit eri a d efi n e d by t h e t ar g et j o ur n al or c o nf er e nc e will b e 
f oll o w e d w h e n it diff ers fr o m I C MJ E crit eri a. 
A ut h ors, i ncl u di n g M e dtr o nic p ers o n n el, m ust at a mi ni m u m m e et all of t h e c o n diti o ns b el o w:  
•  
S u bst a nti al c o ntri b uti o ns t o c o nc e pti o n a n d d esi g n of t h e w ork, or t h e ac q uisiti o n, 
a n al ysis, or i nt er pr et ati o n of d at a f or t h e w ork; A N D  
•  
Dr afti n g t h e w or k or r evisi n g it critic ally f or i m p ort a nt i nt ell ect u al c o nt e nt; A N D  
•  
Fi n al a p pr o v al of t h e v ersi o n t o b e p u blis h e d; A N D  
•  
A gr e e m e nt t o b e acc o u nt a bl e f or al l as p ects of t h e w or k i n e ns uri n g t h at q u esti o ns 
r el at e d t o t h e acc ur acy or i nt e grit y of a ny p art of t h e w or k ar e a p pr o pri at el y 
i nv esti g at e d a n d r es olv e d.  
D ecisi o ns r e g ar di n g a ut h ors hi p a n d c o ntri b ut or -s hi p will b e m a d e by t h e c o m mitt e e. T h e s el ect e d 
a ut h ors will b e r es p o nsi bl e f or dr afti n g t h e p u blic ati o n. All s el ect e d a ut h ors m ust f ulfill t h e a ut h ors hi p 
c o n diti o ns st at e d a b o v e t o b e list e d as a ut h ors, a n d all c o ntri b ut ors w h o f ulfill t h e c o n diti o ns m ust b e 
list e d as a ut h ors. 
All Inv esti g at ors n ot list e d as c o -a ut h ors m ay  b e ac k n o wl e d g e d as t h e “ M e dtr o nic  Cl os e d -L o o p S C S 
St u dy I nv esti g at ors” a n d will b e i n di vi d u all y list e d acc or di n g t o t h e g ui d eli n es of t h e a p plic a bl e sci e ntific 
j o ur n al w h e n p ossi bl e a n d affili ati o n. A ny ot h er c o ntri b ut ors will b e ac k n o wl e d g e d by n a m e wit h t h eir 
s p ecific c o ntri b uti o n i n dic at e d. 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 8  of 1 1 7  
 
 
 
 
 
1 6. 9. 4  
Tr a n s p ar e n c y  
Tr a ns p ar e nc y of cli nic al st u dy r es ults will b e m ai nt ai n e d by t h e f oll o wi n g m e a ns:  
•  
A fi n al r e p ort, d escri bi n g t h e r es ults of all o bj ectiv es a n d a n al ysis, will b e distri b ut e d t o 
all i nv esti g at ors, E Cs a n d C As of p artici p ati n g c o u ntri es w h e n r e q uir e d by l oc al l a w  
•  
R e gist eri n g a n d p osti n g t h e st u dy r es ults o n a p u blicly acc essi bl e d at a b as e, e. g., 
Cli nic al Tri als. g ov , b as e d o n t h e p osti n g r ul es sti p ul at e d  
•  
S u b mitti n g f or p u blic ati o n t h e pri m ar y st u dy r es ults aft er t h e st u dy e n ds  
•  
Discl osi n g c o nflicts of i nt er est ( e. g., fi n a nci al) of t h e c o -a ut h ors of p u blic ati o ns acc or di n g 
t o t h e p olici es s et f ort h by t h e c orr es p o n di n g j o ur n als a n d c o nf er e nc es  
•  
M a ki n g a n i n di vi d u al st u dy sit es st u dy d at a acc essi bl e t o t h e c orr es p o n di n g i nv esti g at or 
aft er t h e c o m pl eti o n of t h e st u dy, if r e q u est e d  
1 6. 1 0  
S u s p e n si o n or E arl y T er mi n ati o n  
1 6. 1 0. 1  
Pl a n n e d St u d y Cl o s ur e  
St u dy Cl os ur e is a pr oc ess i niti at e d b y distri b uti o n of a st u dy cl os ur e l ett er. St u dy cl os ur e is d efi n e d as 
cl os ur e of a st u dy t h at occ urs w h e n M e dtr o nic a n d/ or r e g ul at ory r e q uir e m e nts h a v e b e e n s atisfi e d p er 
t h e CI P a n d/ or by a d ecisi o n by M e dtr o nic or R A), w hic h e v er occ urs first. T h e st u dy cl os ur e pr oc ess is 
c o m pl et e u p o n distri b uti o n of t h e Fi n al R e p ort or aft er fi n al p a y m e nts, w hic h ev er occ urs l ast. O n g oi n g 
E C ov ersi g ht is r e q uir e d u ntil t h e ov er all st u dy cl os ur e pr oc ess is c o m pl et e. R ef er t o S ecti o n  1 0. 3 3  f or 
a d diti o n al i nf or m ati o n r e g ar di n g st u dy exit pr oc e d ur es.  
1 6. 1 0. 2  
E arl y T er mi n ati o n or S u s p e n si o n  
E arl y T er mi n ati o n is t h e cl os ur e of a st u dy t h at occ urs pri or t o m e eti n g d efi n e d e n d p oi nts. T his is 
p ossi bl e f or t h e w h ol e st u dy or a si n gl e st u dy sit e S us p e nsi o n is a t e m p or ar y p ost p o n e m e nt of st u dy 
activiti es r el at e d t o e nr oll m e nt a n d distri b uti o n of t h e pr o d uct. T his is p ossi bl e f or t h e w h ol e st u dy or a 
si n gl e st u dy sit e. I n t h e ev ent t h e w h ol e st u dy or a si n gl e st u dy sit e is s us p e n d e d, bli n di n g of t h e s u bj ect 
r a n d o miz ati o n assi g n m e nt s h o ul d b e m ai nt ai n e d w h e n e v er p ossi bl e. 
1 6. 1 0. 2. 1  
St u d y -wi d e t er mi n ati o n or s u s p e n si o n  
P ossi bl e r e as o ns f or c o nsi d eri n g st u dy -wi d e s us p e nsi o n or t er mi n ati o n of t h e st u dy i ncl u d e b ut ar e n ot 
li mit e d t o: 
•  
A Es ass oci at e d wit h t h e d evic e  or pr o d uct u n d er i nv esti g ati o n w hic h mi g ht e n d a n g er t h e 
s af et y or w elf ar e of t h e s u bj ect 
•  
O bs er v e d/s us p ect e d p erf or m a nc e diff er e nt fr o m t h e pr o d uct’s d esi g n i nt e nt  
•  
D ecisi o n by M e dtr o nic  or R e g ul at ory A ut h orit y   
•  
T ec h nic al iss u es d uri n g t h e m a n uf act uri n g pr oc ess  
1 6. 1 0. 2. 2  
I n v e sti g at or / st u d y sit e t er mi n ati o n or s u s p e n si o n  
P ossi bl e r e as o ns f or i nv esti g at or or st u dy sit e t er mi n ati o n or s us p e nsi o n i ncl u d e b ut ar e n ot li mit e d t o:  
•  
F ail ur e t o o bt ai n i niti al E C a p pr o v al or a n n u al r e n e w al of t h e st u dy  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 8 9  of 1 1 7  
 
 
 
 
 
•  
P ersist e nt n o n -c o m pli a nc e t o t h e cli nic al i nv esti g ati o n ( e. g. f ail ur e t o a d h er e t o 
i ncl usi o n/ excl usi o n crit eri a, f ail ur e t o f oll o w s u bj ects p er sc h e d ul e d f oll o w-u p  visits )  
•  
L ac k of e nr oll m e nt 
•  
N o nc o m pli a nc e t o r e g ul ati o ns a n d t h e t er ms of t h e C T A ( e. g. f ail ur e t o s u b mit d at a i n a 
ti m ely m a n n er, f ail ur e t o f oll o w-u p o n d at a q u eri es a n d m o nit ori n g o bs erv ati o ns i n a 
ti m ely m a n n er, etc.)  
•  
E C s us p e nsi o n of t h e st u dy sit e  
•  
Fr a u d or fr a u d ul e nt misc o n d uct is disc o v er e d ( as d efi n e d by l oc al l a w a n d r e g ul ati o ns)  
•  
I nv esti g at or r e q u est ( e. g., n o l o n g er a bl e t o s u p p ort t h e st u dy)  
1 6. 1 0. 3  
Pr o c e d ur e s f or T er mi n ati o n or S u s p e n si o n  
1 6. 1 0. 3. 1  
M e dtr o ni c -i niti at e d a n d r e g ul at or y a ut h orit y-i niti at e d 
•  
M e dtr o n ic will pr o m ptly i nf or m t h e cli nic al i nv esti g at ors of t h e t er mi n ati o n or 
s us p e nsi o n a n d t h e r e as o ns a n d i nf or m t h e R e g ul at ory A ut h orit y , w h er e r e q uir e d  
•  
I n t h e c as e of st u dy t er mi n ati o n or s us p e nsi o n f or r e as o ns ot h er t h a n a t e m p or ar y E C 
a p pr o v al l a ps e, t h e  i nv esti g at or will pr o m ptly i nf or m t h e E C  
•  
I n t h e c as e of st u dy t er mi n ati o n, t h e i nv esti g at or m ust i nf or m t h e s u bj ects a n d m a y 
i nf or m t h e p ers o n al p hysici a n of t h e s u bj ects t o e ns ur e a p pr o pri at e c ar e a n d f oll o w-u p 
is pr ovi d e d 
•  
I n t h e c as e of a st u dy s us p e nsi o n, s u bj ect e nr oll m e nt m ust st o p u ntil t h e s us p e nsi o n is 
lift e d by M e dtr o nic 
•  
I n t h e c as e of a st u dy s us p e nsi o n, e nr oll e d s u bj ects s h o ul d c o nti n u e t o b e f oll o w e d o ut 
of c o nsi d er ati o n of t h eir s af et y, ri g hts a n d w elf ar e  
1 6. 1 0. 3. 2  
I n v e sti g at or -i niti at e d 
•  
T h e Inv esti g at or will i nf or m M e dtr o nic a n d pr o vi d e a d et ail e d writt e n ex pl a n ati o n of t h e 
t er mi n ati o n or s us p e nsi o n 
•  
T h e I nv esti g at or will pr o m ptl y i nf or m t h e i nstit uti o n , w h er e r e q uir e d p er r e g ul at or y 
r e q uir e m e nts 
•  
T h e I nv esti g at or will pr o m ptl y i nf or m t h e E C  
•  
T h e  I nv esti g at or will pr o m ptl y i nf or m t h e r e g ul at or y a ut h oriti es  
•  
T h e Inv esti g at or will pr o m ptl y i nf or m t h e s u bj ects a n d/ or t h e p ers o n al p hysici a n of t h e 
s u bj ects t o e ns ur e a p pr o pri at e c ar e a n d f oll o w-u p is pr o vi d e d  
•  
I n t h e c as e of a st u dy s us p e nsi o n, s u bj ects e nr oll e d s h o ul d c o nti n u e t o b e f oll o w e d o ut 
of c o nsi d er ati o n of t h eir s af et y, ri g hts a n d w elf ar e  
1 6. 1 0. 3. 3  
Et hi c s C o m mitt e e -i niti at e d 
•  
T h e I nv esti g at or will i nf or m M e dtr o nic a n d pr o vi d e a d et ail e d writt e n ex pl a n ati o n of t h e 
t er mi n ati o n or s us p e nsi o n wit hi n 5 b usi n ess d a ys  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 0  of 1 1 7  
 
 
 
 
 
•  
S u bj ect e nr oll m e nt m ust st o p u ntil t h e s us p e nsi o n is lift e d  
•  
S u bj ects alr e a dy e nr oll e d s h o ul d c o nti n u e t o b e f oll o w e d i n acc or d a nc e wit h E C p olic y or 
its d et er mi n ati o n t h at a n ov erri di n g s af et y c o nc er n or et hic al iss u e is i nv olv e d 
•  
T h e I nv esti g at or will i nf or m his/ h er i nstit uti o n, w h er e r e q uir e d p er l oc al r e q uir e m e nts  
•  
T h e I nv esti g at or will pr o m ptl y i nf or m t h e s u bj ects, or l e g all y -a ut h oriz e d d esi g n e es or 
g u ar di a ns a n d/ or t h e p ers o n al p hysici a n of t h e s u bj ects, wit h t h e r ati o n al e f or t h e st u dy 
t er mi n ati o n or s us p e nsi o n  
•  
T h e I nv esti g at or will pr o m ptl y i nf or m t h e R e g ul at or y A ut h orit y  
1 7.  R ef er e n c e s  
1.           K a p ur al L, Y u C, D o ust M W, et al. N o v el 1 0 -k Hz Hi g h -fr e q u e nc y T h er a py ( H F 1 0 T h er a py) Is 
S u p eri or t o Tr a diti o n al L o w -fr e q u e nc y S pi n al C or d Sti m ul ati o n f or t h e Tr e at m e nt of C hr o nic B ac k 
a n d L e g P ai n: T h e S E N Z A -R C T R a n d o miz e d C o ntr oll e d Tri al. A n est h esi ol o gy . 2 0 1 5; 1 2 3( 4): 8 5 1-
8 6 0.  
2.  
M e k h ail  N, L e vy R M, D e er T R, et al. L o n g -t er m s af et y a n d effic ac y of cl os e d-l o o p s pi n al c or d 
sti m ul ati o n t o tr e at c hr o nic b ac k a n d l e g p ai n ( Ev ok e): a d o u bl e-bli n d, r a n d o mis e d, c o ntr oll e d 
tri al. L a nc et N e ur ol. 2 0 2 0; 1 9( 2): 1 2 3-1 3 4.  
3.  
D’ S o uz a R S, Str a n d N. N e ur o m o d ul ati o n Wit h B urst a n d T o nic Sti m ul ati o n D ecr e as es O pi oi d 
C o ns u m pti o n: A P ost H oc A n al ysis of t h e S ucc ess Usi n g N e ur o m o d ul ati o n Wit h B U R S T 
( S U N B U R S T) R a n d o miz e d C o ntr oll e d Tri al. N e ur o m o d ul ati o n . 2 0 2 1; 2 4( 1): 1 3 5-1 4 1.  
4.  
D e er T R, L evy R M, Kr a m er J, et al. D ors al r o ot g a n gli o n sti m ul ati o n yi el d e d hi g h er tr e at m e nt 
s ucc ess r at e f or c o m pl ex r e gi o n al p ai n s y n dr o m e a n d c a us al gi a at 3 a n d 1 2 m o nt hs: a 
r a n d o miz e d c o m p ar ativ e tri al. P ai n . 2 0 1 7; 1 5 8( 4): 6 6 9-6 8 1.  
5.  
H at h e w ay J A, M a n g al V,  Fis h m a n M A, et al. L o n g-T er m Effic acy of a N o v el S pi n al C or d 
Sti m ul ati o n Cli nic al W orkfl o w Usi n g Kil o h ertz Sti m ul ati o n: T w el v e -M o nt h R es ults Fr o m t h e 
V ect ors St u dy. N e ur o m o d ul ati o n . 2 0 2 1; 2 4( 3): 5 5 6-5 6 5.  
6.  
Fis h m a n M A, C al o d n e y A, Ki m P, et al. Pr os p ectiv e, M ultic e nt er F e asi bility St u dy t o Ev al u at e 
Diff er e nti al T ar g et M ulti pl ex e d S pi n al C or d Sti m ul ati o n Pr o gr a m mi n g i n S u bj ects Wit h C hr o nic 
I ntr act a bl e B ac k P ai n Wit h or Wit h o ut L e g P ai n. P ai n Pr act . 2 0 2 0; 2 0( 7): 7 6 1-7 6 8.  
7.  
B e asl ey K, Z a k ar C, H o b bs S, K a nt h a V, B ur n ei ki e n e S. Pr os p ecti v e r a n d o miz e d f e asi bilit y st u dy 
c o m p ari n g m a n u al vs. a ut o m atic p ositi o n -a d a ptiv e s pi n al c or d sti m ul ati o n wit h s ur gic al l e a ds. 
Act a N e ur oc hir ( Wi e n) . 2 0 1 9; 1 6 1( 8): 1 5 7 1-1 5 7 8.  
8.  
R uss o M, Br o o k er C, C o usi ns MJ, et al. S ust ai n e d L o n g-T er m O utc o m es Wit h Cl os e d -L o o p S pi n al 
C or d Sti m ul ati o n: 1 2 -M o nt h R es ults of t h e Pr os p ectiv e, M ultic e nt er, O p e n -L a b el Av al o n St u dy. 
N e ur os ur g er y . 2 0 2 0; 8 7( 4): E 4 8 5-E 4 9 5.  
9.  
Sc h ultz D M, W e bst er L, K os e k P, D ar U, T a n Y, S u n M. S e ns or -dri v e n p ositi o n -a d a pti v e s pi n al 
c or d sti m ul ati o n f or c hr o nic p ai n. P ai n P hysici a n . 2 0 1 2; 1 5( 1): 1-1 2.  
1 0.  
D e er T R, L evy R M, Kr a m er J, et al. D ors al r o ot g a n gli o n sti m ul ati o n yi el d e d hi g h er tr e at m e nt 
s ucc ess r at e f or c o m pl ex r e gi o n al p ai n s y n dr o m e a n d c a us al gi a at 3 a n d 1 2 m o nt hs: a 
r a n d o miz e d c o m p ar ativ e tri al. P ai n . 2 0 1 7; 1 5 8( 4): 6 6 9-6 8 1.  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 1  of 1 1 7  
 
 
 
 
 
1 1.  
A mir d elf a n K, Y u C, D o ust M W, et al. L o n g-t er m q u alit y of lif e i m pr o v e m e nt f or c hr o nic 
i ntr act a bl e b ack a n d l e g p ai n p ati e nts usi n g s pi n al c or d sti m ul ati o n: 1 2-m o nt h r es ults fr o m t h e 
S E N Z A -R C T. Q u al Lif e R es . 2 0 1 8; 2 7( 8): 2 0 3 5-2 0 4 4.  
1 2.  
Fis h m a n M, C or d n er H, J ustiz R, et al. 1 2 -M o nt h R es ults fr o m M ultic e nt er, O p e n -L a b el, 
R a n d o miz e d C o ntr oll e d Cli nic al Tri al C o m p ari n g Diff er e nti al T ar g et M ulti pl ex e d S pi n al C or d 
Sti m ul ati o n a n d Tr a diti o n al  S pi n al C or d Sti m ul ati o n i n S u bj ects wit h C hr o nic I ntr act a bl e B ac k 
P ai n a n d L e g P ai n. P ai n Pr act . 2 0 2 1;( 1 5 3 3-2 5 0 0 ( El ectr o nic)).  
1 3.  
P ar k er JL, K ar a nt o nis D M, Si n gl e P S, O br a d ovic M, C o usi ns MJ. C o m p o u n d acti o n p ot e nti als 
r ec or d e d i n t h e h u m a n s pi n al c ord d uri n g n e ur osti m ul ati o n f or p ai n r eli ef. P ai n . 
2 0 1 2; 1 5 3( 3): 5 9 3 -6 0 1.  
1 4.  
P ar k er JL, O br a d ovic M, H es a m S N, et al. E v o k e d C o m p o u n d Acti o n P ot e nti als R ev e al S pi n al C or d 
D ors al C ol u m n N e ur o a n at o m y. N e ur o m o d ul ati o n . 2 0 2 0; 2 3( 1): 8 2-9 5.  
1 5.  
P ar k er JL, K ar a nt o nis D M, Si n gl e P S, et al. El ectric all y ev ok e d c o m p o u n d acti o n p ot e nti als 
r ec or d e d fr o m t h e s h e e p s pi n al c or d. N e ur o m o d ul ati o n . 2 0 1 3; 1 6( 4): 2 9 5-3 0 3; disc ussi o n 3 0 3.  
1 6.  
C h a kr a v art hy K, Bi n k H, Di ns m o or D. S e nsi n g E v o k e d C o m p o u n d Acti o n P ot e nti als fr o m t h e  
S pi n al C or d: N o v el Pr ecli nic al a n d Cli nic al C o nsi d er ati o ns f or t h e P ai n M a n a g e m e nt R es e arc h er 
a n d Cli nici a n. J P ai n R es. 2 0 2 0; 1 3( 1 1 7 8-7 0 9 0 ( Pri nt)): 3 2 6 9 -3 2 7 9.  
1 7.  
C h a kr a v art hy K, Fitz G er al d J, Will A, et al. A Cli nic al F e asi bilit y St u dy of S pi n al E v ok e d  C o m p o u n d 
Acti o n P ot e nti al Esti m ati o n M et h o ds. N e ur o m o d ul ati o n . 2 0 2 1;( 1 5 2 5-1 4 0 3 ( El ectr o nic)).   
1 8 .  
M e k h ail N, L e vy R M, D e er T R, et al. L o n g-t er m s af et y a n d effic ac y of cl os e d-l o o p s pi n al c or d 
sti m ul ati o n t o tr e at c hr o nic b ac k a n d l e g p ai n ( Ev ok e): a d o u bl e-bli n d, r a n d o mis e d, c o ntr oll e d 
tri al. L a nc et N e ur ol. 2 0 2 0; 1 9( 2): 1 2 3-1 3 4.   
1 9.  
M e k h ail N, L e vy R M, D e er T R, et al. D ur a bilit y of Cli nic al a n d Q u ality -of -Lif e O utc o m es of Cl os e d-
L o o p S pi n al C or d Sti m ul ati o n f or C hr o nic B ack a n d L e g P ai n: A S ec o n d ar y A n alysis of t h e Ev o k e 
R a n d o miz e d Cli nic al Tri al. J A M A N e ur ol. 2 0 2 2;( 2 1 6 8-6 1 5 7 ( El ectr o nic)).  
2 0.  
C h a kr a v art hy K, Bi n k H, Di ns m o or D. S e nsi n g  E v o k e d C o m p o u n d Acti o n P ot e nti als fr o m t h e 
S pi n al C or d: N o v el Pr ecli nic al a n d Cli nic al C o nsi d er ati o ns f or t h e P ai n M a n a g e m e nt R es e arc h er 
a n d Cli nici a n. J P ai n R es. 2 0 2 0; 1 3( 1 1 7 8-7 0 9 0 ( Pri nt)): 3 2 6 9 -3 2 7 9.  
2 1.  
K eis er M G, Pilitsis J, Fis h m a n M, Di ns m o or D. Ec a ps i n t h e d ors al c ol u m ns of a w a k e vs. 
a n est h etiz e d ovi n es. N e ur o m o d ul ati o n . 2 0 2 0; 2 3( 3): e 2 3 1.  
2 2.  
Pilitsis J, H a g e m a n K, Sk er k er A, Di ns m o or D. T h e Eff ect of M A C o n E C A P S i n t h e D ors al C ol u m ns 
of Ovi n es. N e ur o m o d ul ati o n . 2 0 2 1; 2 4( 4): e 1 8.  
2 3.  
Di ns m o or D , G o o d m a n K M, V er a-P ort oc arr er o L, Fitz g er al d J, C h a kr a v art hy K. E C A Ps r es ulti n g 
fr o m “c o nst a nt d os e” sti m ul ati o n i n t h e d ors al c ol u m ns of a w a k e ovi n e. N e ur o m o d ul ati o n . 
2 0 2 0; 2 3( 3): e 1 7 7.  
2 4 .  
A mir d elf a n K, Y u C, D o ust M W, et al. L o n g-t er m q u alit y of lif e im pr o v e m e nt f or c hr o nic 
i ntr act a bl e b ack a n d l e g p ai n p ati e nts usi n g s pi n al c or d sti m ul ati o n: 1 2-m o nt h r es ults fr o m t h e 
S E N Z A -R C T. Q u al Lif e R es . 2 0 1 8; 2 7( 8): 2 0 3 5-2 0 4 4.  
2 5.  
D e er T, Sl avi n K V, A mir d elf a n K, et al. S ucc ess Usi n g N e ur o m o d ul ati o n Wit h B U RS T ( S U N B U R S T) 
St u dy: R es ults Fr o m a Pr os p ecti v e, R a n d o miz e d C o ntr oll e d Tri al Usi n g a N o v el B urst W av ef or m. 
N e ur o m o d ul ati o n . 2 0 1 8; 2 1( 1): 5 6-6 6.  
2 6.  
Fis h m a n M, C or d n er H, J ustiz R, et al. 1 2 -M o nt h R es ults fr o m M ultic e nt er, O p e n -L a b el, 
R a n d o miz e d C o ntr oll e d Cli nic al Tri al C o m p ari n g Diff er e nti al T ar g et M ulti pl ex e d S pi n al C or d 
Sti m ul ati o n a n d Tr a diti o n al S pi n al C or d Sti m ul ati o n i n S u bj ects wit h C hr o nic I n tr act a bl e B ac k 
P ai n a n d L e g P ai n. P ai n Pr act . 2 0 2 1;( 1 5 3 3-2 5 0 0 ( El ectr o nic)).  

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 2  of 1 1 7  
 
 
 
 
 
2 7.  
K a p ur al L, Y u C, D o ust M W, et al. N o v el 1 0 -k Hz Hi g h -fr e q u e nc y T h er a py ( H F 1 0 T h er a py) Is 
S u p eri or t o Tr a diti o n al L o w -fr e q u e nc y S pi n al C or d Sti m ul ati o n f or t h e Tr e at m e nt of C hr o nic B ac k 
a n d L e g P ai n: T h e S E N Z A -R C T R a n d o miz e d C o ntr oll e d Tri al. A n est h esi ol o gy . 2 0 1 5; 1 2 3( 4): 8 5 1-
8 6 0.  
2 8.  
Sc h ultz D M, W e bst er L, K os e k P, D ar U, T a n Y, S u n M. S e ns or -dri v e n p ositi o n -a d a pti v e s pi n al 
c or d sti m ul ati o n f or c hr o nic p ai n. P ai n P hysici a n . 2 0 1 2; 1 5( 1): 1-1 2.  
2 9.  
Br o ok er C, R uss o M, C o usi ns MJ, et al. E C A P -C o ntr oll e d Cl os e d -L o o p S pi n al C or d Sti m ul ati o n 
Effic ac y a n d O pi oi d R e d ucti o n Ov er 2 4 -M o nt hs: Fi n al R es ults of t h e Pr os p ectiv e, M ultic e nt er, 
O p e n -L a b el Av al o n St u dy. P ai n Pr act . 2 0 2 1; 2 1( 6): 6 8 0-6 9 1.  
3 0.  
Sc h a d e C M, Sc h ultz D M, T a m a y o N, I y er S, P a n k e n E. A ut o m atic a d a pt ati o n of n e ur osti m ul ati o n 
t h er a py i n r es p o ns e t o c h a n g es i n p ati e nt p ositi o n: r es ults of t h e P ost ur e R es p o nsi v e S pi n al C or d 
Sti m ul ati o n ( P R S) R es e arc h St u dy. P ai n P hysici a n . 2 0 1 1; 1 4( 5): 4 0 7-4 1 7.  
  
 
  
  
 
  
  
 
  
  
 
  
  
 
  
  
 
  
  
 
 
  
 
  
3 9.  
H urst H, B olt o n J. Ass essi n g t h e cli nic al si g nifi c a nc e of c h a n g e sc or es r ec or d e d o n s u bj ecti v e 
o utc o m e m e as ur es. J M a ni p ul ativ e P hysi ol T h er. 2 0 0 4; 2 7( 1): 2 6-3 5.  
  
 
  
4 1.  
Wi ni n g er KL, D es h p a n d e K K, D es h p a n d e K K. R a di ati o n ex p os ur e i n p erc ut a n e o us s pi n al c or d 
sti m ul ati o n m a p pi n g: A pr eli mi n ar y r e p ort. P ai n P hys . 2 0 1 0; 1 3( 1): 7-1 8.   
4 2.  
Sc h mi d G, Sc h mitz A, B orc h ar dt D, et al. Eff ecti v e d os e of  C T - a n d fl u or osc o py -g ui d e d 
p eri n e ur al/ e pi d ur al i nj ecti o ns of t h e l u m b ar s pi n e: a c o m p ar ativ e st u dy. C ar di ov asc I nt er v e nt 
R a di ol . 2 0 0 6; 2 9( 1): 8 4-9 1.  
4 3.  
Pr a d h a n A S. O n t h e ris k t o l o w d os es ( < 1 0 0 m Sv) of i o nizi n g r a di ati o n d uri n g m e dic al i m a gi n g 
pr oc e d ur es - I O M P p olicy st at e m e nt. J M e d P hys. 2 0 1 3; 3 8( 2): 5 7-5 8.  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 3  of 1 1 7  
 
 
 
 
 
1 8.   A p p e n di c e s  
1 8. 1  A p p e n di x A: F or e s e e a bl e A d v er s e E v e nt s  
P ot e nti al ris ks ass oci at e d wit h t h e I nc e p ti v s yst e m, ass oci at e d h ar ms, a n d a dv ers e ev e nts, as w ell as ris k 
mi ni miz ati o n ar e disc uss e d i n m or e d et ail i n S ecti o n 1 1 .  T h e i nf or m ati o n pr o vi d e d i n t his s ecti o n 
i ncl u d es a d diti o n al r ef er e nc e i nf or m ati o n a n d m ay c oll ecti v el y assist i n i d e ntif yi n g t h os e ev e nts f or a 
giv e n d evic e or t h er a py t h at ar e u n ex p ect e d i n n at ur e.  T h e f or es e e a bl e a dv ers e ev e nt i nf or m ati o n 
c o nsists of r at es of a dv ers e e v e nts r e p ort e d fr o m pr e vi o us M e dtr o nic st u di es ev al u ati n g S C S s yst e ms.   
T h e i m pl a nt ati o n of t h e I nc e pti v syst e m i nv ol v es s ur g er y, t h er ef or e, st a n d ar d a dv ers e e v e nts ass oci at e d 
wit h a s ur gic al pr oc e d ur e m a y b e ex p eri e nc e d ( e. g., a n est h esi a c o m plic ati o ns, i nj ur y, i nf ecti o ns, 
bl e e di n g, ex ac er b ati o n of pr e -existi n g c o n diti o ns, h e ali n g c o m plic ati o ns). H o w ev er, t h e f oc us of t his 
s ecti o n is t o a d dr ess i n m or e d et ail, t h os e e v e nts t h at ar e f or es e e a bl e d u e t o t h e i m pl a nt ati o n, us e, 
p erf or m a nc e, a n d/ or pr es e nc e of t h e s yst e m u n d er i nv esti g ati o n or c o m p ar a bl e s yst e ms.  
Tr e at m e nt r e q uir e d f or pr oc e d ur e a n d/ or d e vic e/syst e m r el at e d a dv ers e ev e nts m a y i ncl u d e 
m e dic ati o n, d e vic e r e pr o gr a m mi n g, d e vic e m o dific ati o n ( e. g., r e p ositi o ni n g, el ectric al a b a n d o n m e nt, 
s ur gic al r e m ov al), or ot h er s ur gic al or m e dic al r e m e di es.  
A d v ers e E v e nts R e p ort e d i n Pr e vi o us M e dtr o nic Cli nic al St u di es  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 4  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 5  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 6  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 7  of 1 1 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 8. 2  A p p e n di x B : P arti ci p ati n g I n v e sti g at or s a n d I n stit uti o n s  
A fi n al list of p artici p ati n g I nv esti g at ors ( n a m es, a d dr ess, pr of essi o n al p ositi o ns) a n d i nstit uti o ns ( n a m es 
a n d a d d r ess) h as n ot b ee n  fi n aliz e d a n d will b e distri b ut e d u n d er s e p ar at e c ov er.  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 8  of 1 1 7  
 
 
 
 
 
1 9.  V er si o n Hi st or y  
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
1. 0/ 1 9 A U G 2 0 2 1  N ot 
A p plic a bl e, 
N e w 
D oc u m e nt  
N ot A p plic a bl e, 
N e w D oc u m e nt  
N ot 
A p plic a bl e, 
N e w 
D oc u m e nt  
N ot 
A p plic a bl e, 
N e w 
D oc u m e nt  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  T er m “ N e ur o 
S e ns e” w as 
r e m o v e d 
t hr o u g h o ut 
u nl ess it is i n 
r ef er e nc e t o a 
pr o gr a m mi n g 
s etti n g or 
r a n d o miz ati o n 
assi g n m e nt  
B usi n ess 
d ecisi o n  
N o n e  
All  
  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
A d d e d 
i ncl usi o n 
crit eri a 
r ec o m m e n d at
i o n t o o nl y 
e nr oll p ati e nts 
ca p a bl e of 
c o m pr e h e n di n
g a n d 
c o ns e nti n g i n 
E n glis h  
Tr a nsl at e d 
d oc u m e nts n ot 
a v ail a bl e  
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 9 9  of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2. 0/ 0 8 F E B 2 0 2 2  
E dit e d 
i ncl usi o n 
crit eri o n 3 t o 
i ncl u d e 
p ati e nts wit h 
b ac k a n d/ or 
l e g p ai n 
t o b e ali g n e d 
wit h d evic e 
i n dic ati o ns a n d 
r e pr es e nt ati v e 
of t h e g e n er al 
p ai n p o p ul ati o n  
Aff ects 
s o m e of t h e 
S ec o n d ar y 
a n d 
A d diti o n al 
O bj ectiv es. 
T h e a n al ysis 
p o p ul ati o ns 
f or t h e 
aff ect e d 
S ec o n d ar y/ 
A d diti o n al 
O bj ectiv es 
w er e 
cl arifi e d t o 
i ncl u d e 
t h os e wit h 
b as eli n e 
b ac k  or l e g 
p ai n V A S ≥ 
6 0 m m .  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
I ncl usi o n 
Crit eri o n  3 h as 
b e e n m o difi e d 
t o d efi n e 
eli gi bl e 
p ati e nts as 
t h os e wit h 
b ac k a n d/ or 
l e g p ai n  
p ati e nts wit h 
1. b as eli n e 
o v er all V A S ≥ 
6 0 m m a n d  
E dit e d I ncl usi o n 
Crit eri o n 3 f or 
cl arit y  
Aff ects 
s o m e of t h e 
S ec o n d ar y 
a n d 
A d dit i o n al 
O bj ectiv es. 
T h e a n al ysis 
p o p ul ati o ns 
f or t h e 
aff ect e d 
S ec o n d ar y/ 
A d diti o n al 
O bj ectiv es 
w er e 
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 0 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2)  b ack 
a n d/ or l e g 
p ai n ≥ 6 0 m m  
cl arifi e d t o 
i ncl u d e 
t h os e wit h 
b as eli n e 
b ac k or l e g 
p ai n V A S ≥ 
6 0 m m.  
2. 0/ 0 8 F E B 2 0 2 2  
R e p hr as e d 
S ecti o n s 4. 2 , 6 
a n d 9. 1  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
D el et e d 
d u plic at e d 
t ext i n S ecti o n 
6. 2  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
U p d at e d s o m e 
m o d el 
a p plic ati o n 
n u m b ers i n 
T a bl e 3, 4  a n d 
Fi g ur e 4  
A d mi nistr ativ e 
c h a n g e 
N o n e  
I B 
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 1 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2. 0/ 0 8 F E B 2 0 2 2  
C h a n g e d 
“ will” t o 
“ m ay” f or t h e 
fl exi o n 
m a n e uv er i n 
S ecti o ns 1 0. 9, 
1 0. 1 0 , 1 0. 1 2  
a n d 1 1. 2. 3  
S o m e sit es m ay 
n ot r o uti n ely 
p erf or m t his  
N o n e  
I nv esti g at or’s 
Br oc h ur e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
A d d e d t h e 
U E FI -1 5 i n 
S ecti o n 
1 0. 1 6. 1  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
R e m ov e d 
“fr o m t h e 
st art of t h e 
d e vic e tri al 
u ntil st u dy 
exit” fr o m 
S ecti o n 1 0. 2 2  
A d e vic e 
d efici e nc y c o ul d 
occ ur b ef or e 
us e of t h e 
d e vic e  
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
A d d e d 
ex a m pl es of 
el ectr o m a g n et
ic i nt erf er e nc e 
i n S ecti o n 
1 1. 2. 2  
A d mi nistr ativ e 
c h a n g e 
N o n e  
I nv esti g at or’s 
Br oc h ur e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 2 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2. 0/ 0 8 F E B 2 0 2 2  
A  s e nt e nc e 
w as m o difi e d 
t o pr o vi d e a n 
ex a m pl e of 
w h at 
a d diti o n al 
r a di ati o n 
ex p os ur e a 
p ati e nt m a y 
f ac e, as n ot all 
st u dy 
p artici p a nts 
m a y r e q uir e 5 
a d diti o n al 
sc a ns i n 
S ecti o n 1 1. 2. 3  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
A d d e d 
i nstr ucti o ns 
f or d evic e 
pr o gr a m mi n g 
pri or t o 
m e dic al 
pr oc e d ur e s i n 
S ecti o n 1 1. 3  
N e w 
i nf or m ati o n 
N o n e  
I nf or m e d 
C o ns e nt F or m 
a n d 
I nv esti g at or’s 
Br oc h ur e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
R e m ov e d C R O 
i nf or m ati o n i n 
S ecti o n 1 3  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 3 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2. 0/ 0 8 F E B 2 0 2 2  
R e m ov e d t h e 
r e q uir e m e nt 
f or i niti als t o 
b e us e d i n 
S ecti o n 1 6. 7. 1  
N a m e is 
acc e pt a bl e f or 
p ers o n w h o 
r ec eiv e d t h e 
d e vic es  
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
U p d at e d t h e 
A ustr ali a n 
Cli nic al Tri al 
H a n d b o o k  
v ersi o n i n 
S ecti o n 1 6  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
2. 0/ 0 8 F E B 2 0 2 2  
U p d at e d t h e 
s y n o psis a n d 
st atistic al 
a n al ys es 
s ecti o ns t o 
r efl ect t h e 
c h a n g e i n 
s u bj ect 
p o p ul ati o ns 
us e d f or e ac h 
a n al ysis ( d u e 
t o t h e 
m o dific ati o n 
of t h e 
i ncl usi o n/ excl
usi o n crit eri a).  
N ec ess ary 
u p d at e d u e t o 
m o dific ati o n of 
t h e 
i ncl usi o n/ excl us
i o n crit eri a. 
C o ul d 
i m p act t h e 
a bilit y t o 
a d e q u at el y 
esti m at e 
t h e 
r es p o n d er 
r at e i n t h e 
l o w-b ack or 
l e g 
p o p ul ati o ns 
if w e ar e 
u n a bl e t o 
e nr oll a 
l ar g e 
e n o u g h 
n u m b er of 
s u bj ects 
wit hi n e ac h 
i n dic ati o n. 
Will i m p act 
t h e S A P ( n ot 
y et c o m pl et e) 
a n d ot h er 
d oc u m e nts 
will b e 
aff ect e d by 
t h e 
i ncl usi o n/ excl
usi o n crit eri a 
m o dific ati o n.  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 4 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
2. 0/ 0 8 F E B 2 0 2 2  
“ H R” r e m o v e d 
fr o m H R E C 
a n d I nc e pti v e 
c orr ect e d t o 
I nc e pti v 
t hr o u g h o ut 
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
C h a n g e d visit 
wi n d o w 
b et w e e n 
E nr oll m e nt 
a n d Tri al t o 2 8 
d a ys  
T h e pr evi o us 
1 4 -d a y wi n d o w 
w as t o o s h ort 
t o sc h e d ul e f or 
t h e Tri al 
pr oc e d ur e.  
N o n e  
I nf or m e d 
C o ns e nt  F or m  
 
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d t o 
0 5 6 -F 2 7 5 v E 
Cli nic al 
I nv esti g ati o n 
Pl a n T e m pl at e  
R e q uir e m e nt t o 
u p d at e t o m ost 
c urr e nt 
t e m pl at e. N o 
t e m pl at e 
c h a n g es 
i m p act e d 
c o nt e nt of t h e 
CI P . 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
A d d e d t h e 
f oll o wi n g 
N ot e t o t h e 
Excl usi o n 
Crit eri a # 5 
“N ot e: T h e 
S p o ns or 
r ec o m m e n ds 
excl u di n g 
p ati e nts  o n 
≥1 0 0 M M E of 
o pi oi ds/ d ay. ” 
T o e ns ur e 
a bil it y t o 
c o m pl y wit h 
st u dy-r el at e d 
acti viti es 
d escri b e d i n t h e 
pr ot oc ol .  
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 5 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
3. 0/ 2 1 O C T 2 0 2 2  
A d d e d 
cl arific ati o n t o 
Excl usi o n 
Crit eri a # 7 
“N ot e: t his 
i ncl u d es 
p ati e nts t h at 
ar e t h e 
b e n efici ar y of 
a s ucc essf ul 
i nj ur y cl ai m. “ 
Pr ovi d e d 
cl arific ati o n. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
I ncl usi o n 
Crit eri a # 2 t o 
a d d cl arit y o n 
t y p es of p ai n 
s y n dr o m es 
t h at w o ul d b e 
eli gi bl e by 
a d di n g t ext 
“ d u e t o F ail e d 
B ac k S ur g ery 
Sy n dr o m e 
( F B S S), 
C o m pl ex 
R e gi o n al P ai n 
Sy n dr o m e 
( C R P S), or 
ot h er c hr o nic 
n e ur o p at hic 
p ai n wit h o ut 
hist or y of 
s ur gic al 
i nt er v e nti o ns.
” A n 
Cl arif y 
a p pr o pri at e 
c a n di d at es f or 
c o nsi d er ati o n. 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 6 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
a d diti o n al 
n ot e w as 
a d d e d st ati n g 
“T h e s p o ns or 
r ec o m m e n ds 
n ot e nr olli n g 
p ati e nts wit h 
c hr o nic p ai n 
d u e t o 
c o n diti o ns 
t h at d o n ot 
h av e 
a d e q u at e 
evi d e nc e t o 
s u p p ort t h e 
us e of S C S 
( e. g., p ost-
h e r p etic 
n e ur al gi a, 
f oc al C R P S 
etc.) ” 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d  
Excl usi o n 
Crit eri a # 1 t o 
i ncl u d e 
Di a b etic 
P eri p h er al 
N e ur o p at hy  
Cl arif y 
a p pr o pri at e 
c a n di d at es f or 
c o nsi d er ati o n. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
S ecti o n 1 0. 7 
t o all o w us e of 
existi n g 
ps yc h ol o gic al 
e v al u ati o n 
wit hi n t h e 
All o ws gr e at er 
fl exi bilit y f or 
sit es i n 
sc h e d uli n g as 
w ell as n ot t o 
i ncr e as e b ur d e n 
by r e p e ati n g 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 7 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
pr e vi o us 6 
m o nt hs wit h 
r ec o nfir m ati o
n of s uit a bility 
f or S C S i n li e u 
of r e q uiri n g a 
n e w 
ps yc h ol o gic al 
e v al u at i o n.  
e v al u ati o ns 
u n n ec ess aril y . 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
S ecti o n 1 0. 7 
t o all o w C T-
sc a n i n 
a d diti o n t o 
M RI a n d X -r a y 
as w ell as t o 
r e q uir e 
i m a gi n g t o b e 
r e vi e w e d 
w h er e as it 
w as l eft t o 
i nv esti g at or 
discr eti o n 
al o n e.  
All o ws gr e at er 
fl exi bilit y f or 
sit es i n 
l e v er a gi n g 
existi n g i m a gi n g 
or i n o bt ai ni n g 
n e w i m a gi n g if  
a p ot e nti al 
s u bj ect c a n n ot 
h a v e M RI or X -
r a y. Als o 
e ns ur es 
i nv esti g at ors 
r e vi e w i m a gi n g 
o n fil e, or 
o bt ai ns n e w 
i m a gi n g, t o 
ass ess if t h e 
s u bj ect s h o ul d 
c o nti n u e i n t h e 
st u dy. 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 8 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
3. 0/ 2 1 O C T 2 0 2 2  
R e m ov e d 
“I nt e nsity 
Sc or e f or 
O v ersti m ul ati
o n” i n S ecti o n 
1 0. 2 1. 1 as it 
w as a n err or 
i n t h e 
p ar a gr a p h 
str uct ur e, n ot 
n e e d e d.  
Gr a m m atic al 
u p d at e . 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
S ecti o n 
1 0. 2 1. 1 2 t o 
c orr ect t h e 
err or n oti n g 
t h at P R O MI S-
2 9 is a 1 0 
p oi nt sc al e, t o 
i n dic at e t h at it 
is a n 1 1 p oi nt 
sc al e si nc e it 
r a n g es fr o m 0-
1 0.  
Err or 
c orr ecti o n. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
R e pl ac e d 
“ e nr oll e d” 
wit h 
“i m pl a nt e d” i n 
s ecti o n 1 4. 1. 3 
t o ali g n wit h 
S ecti o n 6  
Li mits t h e t ot al 
n u m b er of 
i m pl a nt e d 
p ati e nts fr o m 
e ac h sit e t o 
mi ni miz e bi as . 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 0 9 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
Fi g ur e 
n u m b ers i n 
t h e t ext of 
S ecti o n 1 0. 1 
as t h ey 
r ef er e nc e d 
t h e wr o n g 
fi g ur es. 
Err or 
c orr ecti o n. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
T a bl e 
n u m b ers i n 
t h e t ext of 
S af et y S ecti o n 
1 2. 1, 1 2. 2, 
a n d 1 2. 5. 1 t o 
ali g n wit h 
c orr ect T a bl es 
wit hi n t h os e 
s ecti o ns. 
Err or 
c orr ecti o n. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
R e or g a niz e d  
t ext i n S ecti o n 
1 2. 1  f or 
e v e nts t h at 
ar e n ot 
r e p ort a bl e 
a n d a d d e d a 
N O T E b el o w 
t h e b ull et e d 
it e ms t o 
cl arif y w h e n 
t o r e p ort. 
Pr ovi d e d 
cl arific ati o n. 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 0 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
3. 0/ 2 1 O C T 2 0 2 2  
Cl arifi e d 
ast eris k f o ot er 
u n d er T a bl e 8: 
E v e nt 
Cl assific ati o n 
R es p o nsi biliti e
s t o i n dic at e 
t h at t h er a py-
r el at e d als o 
f all i nt o A D E 
cl assific ati o n. 
Cl arific ati o n . 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
Cli nici a n 
T a bl et M o d el 
t o i ncl u d e 
C T 9 0 0 E i n 
a d diti o n t o 
C T 9 0 0 D i n 
T a bl e 3 a n d 
T a bl e 4  
H ar d w ar e 
m a n uf act ur er 
will ev e nt u all y 
p h as e o ut t h e 
C T 9 0 0 D, s o t his 
u p d at e all o ws 
f or t he u p d at e d 
h ar d w ar e t o b e 
us e d.  
N o n e  
I nv esti g at or’s 
Br oc h ur e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
A d d e d “ or 
n e w er” t o 
s oft w ar e 
v ersi o ns i n 
T a bl e 3. Als o 
c orr ect e d 
pr o gr a m m er 
pl atf or m 
s oft w ar e-
c o m m u nic ati o
n m a n a g er 
a p plic ati o n 
v ersi o n fr o m 
1. 0. 1 2 1 2 3 t o 
1. 0. 1 2 1 3  
T o all o w f or 
s oft w ar e 
u p d at es t o 
l a u nc h d uri n g 
st u dy c o n d uct. 
V ersi o n utiliz e d 
will b e n ot e d o n 
all s essi o n 
r e p orts a n d/ or 
l o gs. Als o 
c orr ect e d t y p o 
i n pr o gr a m m er 
pl atf or m 
s oft w ar e-
c o m m u nic ati o n 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 1 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
m a n a g er 
a p plic ati o n 
v ersi o n 
n u m b er.  
3. 0/ 2 1 O C T 2 0 2 2  
A d d e d N ot e 
“If t h e s u bj ect 
r e p orts 
ov ersti m ul ati o
n/ disc o mf ort 
fr o m 
sti m ul ati o n i n 
b et w e e n st u dy 
visits b ut h as 
n ot 
d oc u m e nt e d 
i n t h e 
Sti m ul ati o n 
Di ar y, pl e as e 
r e q u est t h e 
s u bj ect t o 
c o m pl et e t h e 
di ar y d uri n g 
t h e visit.” i n 
s ecti o n 
1 0. 1 6. 1  
A d diti o n al 
g ui d a nc e t o 
sit es o n 
sti m ul ati o n 
di ar y 
ex p ect ati o ns.  
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
S ecti o n 1 0. 1 7 
t o cl arif y 
P h o n e C alls 
st art at ti m e 
of D evic e 
Acti v ati o n as 
Pr ovi d es m or e 
d et ail t o sit es 
o n h o w t o 
ass ess w h e n 
u nsc h e d ul e d 
visits a n d/ or 
t h er a py 
N o n e  
I nf or m e d 
C o ns e nt F or m  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 2 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
w ell as 
i m pl e m e nt 
N R S c oll ecti o n 
i n a d diti o n t o 
s atisf acti o n. 
A d d e d a n 
ex p ect ati o n 
o n 
ass ess m e nt 
f or 
o v ersti m ul ati o
n e v e nts. 
A d d e d d et ail 
o n st e ps t o 
t a k e if N R S is 
4 or m or e t o 
e ns ur e 
s u bj ects h av e 
t h er a py 
o pti miz e d 
w h e n n e e d e d.  
o pti miz ati o n 
m a y b e n e e d e d. 
T his als o 
e ns ur es t h e y 
ar e a w ar e of 
o v ersti m ul ati o n 
e v e nts t h e 
s u bj ect m a y 
h a v e 
ex p eri e nc e d.  
3. 0/ 2 1 O C T 2 0 2 2  
I n S ecti o n 
1 0. 2 3, 
r e m o v e d “ a n d 
( 3) a 
st at e m e nt 
att esti n g t o 
t h e acc ur ac y 
a n d 
c o m pl et e n ess 
of t h e c o py” 
as it is n ot a n 
I S O 
r e q uir e m e nt. 
Als o r e m o v e d 
U p d at e b as e d 
o n st u dy d esi g n 
a n d I S O 
r e q uir e m e nts. 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 3 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
Syst e m 
M o dific ati o n 
fr o m t h e 
b ull e t e d list as 
it w as 
t e m pl at e 
l a n g u a g e t h at 
d o es n’t a p pl y 
t o t his 
pr ot oc ol.  
3. 0/ 2 1 O C T 2 0 2 2  
U p d at e d 
S ecti o n 1 4. 9 
t o i n dic at e t h e 
st u dy sit e 
e nr oll m e nt 
c a p is 1 8 
i nst e a d of 1 7. 
Ali g ns wit h sit e 
c o m m u nic ati o n 
a n d ex p ect ati o n 
t h at t h e c a p 
s h o ul d b e 2 0 %. 
N o n e  
N o n e  
 
 
 
 
 
3. 0/ 2 1 O C T 2 0 2 2  
R e m ov e d t h e 
w or d s 
“ ass ess e d f or” 
fr o m 
“ ass ess e d f or 
A Es/ d evic e 
d efici e nci es” 
i n a p plic a bl e 
visit s ecti o ns 
as A E a n d D D 
u p d at es mi g ht 
n ot b e n e w, 
b ut u p d at es 
o n existi n g.  
Cl arit y o n d at a 
c oll ecti o n 
ex p ect ati o n .  
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 4 of 1 1 7  
 
M e dtr o ni c 
e dtr o ni c B u si n e s s R e stri ct e d
B u si n e s s R e stri ct e d  
 
 
 
0 5 6 -F 2 7 5, v E Cli ni c al I n v esti g ati o n Pl a n T e m pl at e  
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
3. 0/ 2 1 O C T 2 0 2 2  
R e m ov e d 
“ A D E” fr o m 
s ec o n d b ull et 
i n S ecti o n 
1 6. 7. 1 as A D E 
is 
e nc o m p ass e d 
wit hi n t h e A E 
c at e g or y. 
R e m ov e d 
r e d u n d a nc y. 
N o n e  
N o n e  
 
 
 
 
 
4. 0 /0 6J A N 2 0 2 3  
U p d at e d 
S ecti o n 6. 1 
D ur ati o n t o 
c h a n g e 
e nr oll m e nt 
p eri o d fr o m 
1 2 m o nt h t o 
a p pr oxi m at ely 
2 4 m o nt hs  
E nr oll m e nt 
t a ki n g l o n g er 
t h a n 
a ntici p at e d  
N o n e  
I nf or m e d 
C o ns e nt F or m  
 
 
4. 0/ 0 6J A N 2 0 2 3  
U p d at e d 
s a m pl e siz e 
c alc ul ati o n i n 
s ecti o n 1 4. 8 
t o r efl ect a 
hi g h er 
attriti o n r at e  
A hi g h er -t h a n-
ex p ect e d 
attriti o n r at e 
h as b e e n 
o bs erv e d s o f ar.  
T h e n e w 
ex p ect e d 
attriti o n r at e 
m or e cl os el y 
r efl ects t h e 
attriti o n r at e 
b ei n g o bs erv e d 
i n t h e st u dy. 
N o n e  
I nf or m e d 
C o ns e nt F or m  
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 5 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
4. 0/ 0 6J A N 2 0 2 3  
U p d at e d 
n u m b er of 
s u bj ects t o b e 
e nr oll e d fr o m 
9 0 t o 1 4 0 
t hr o u g h o ut 
t h e 
d oc u m e nt.  
A hi g h er -t h a n-
ex p ect e d 
attriti o n r at e 
h as b e e n 
o bs erv e d s o f ar.  
T h e n e w 
ex p ect e d 
attriti o n r at e 
m or e cl os el y 
r efl ects t h e 
attriti o n r at e 
b ei n g o bs erv e d 
i n t h e st u dy. 
N o n e  
I nf or m e d 
C o ns e nt  
 
 
 
 
 
4. 0/ 0 6J A N 2 0 2 3  
Mi n or 
gr a m m atic al 
err ors  
A d mi nistr ativ e 
c h a n g e 
N o n e  
N o n e  
 
 
 
4. 0/ 0 6J A N 2 0 2 3  
C h a n g e d fr o m 
5 0 i m pl a nt e d 
s u bj ects f or 
l o w er b ac k 
a n d l e g p ai n 
t o u p t o 5 7 
a n d c h a n g e d 
1 2 s u bj ects 
f or u p p er 
li m b/ n ec k 
m a y b e  
i m pl a nt e d a n d 
u p t o 2 5  
u p p er li m b 
a n d/ or n ec k 
C o nc er n wit h 
hi g h er attriti o n 
r at e 
N o n e  
N o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 6 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
p ai n s u bj ects 
m a y b e 
e nr oll e d  
4. 0/ 0 6J A N 2 0 2 3  
R e m ov e d 
r e q uir e m e nt 
f or a p h o n e 
c all w h e n 
s u bj ect h as a n 
i n offic e visit 
f or 
O pti miz ati o n  
P ati e nt will b e 
s e e n w e ekl y 
d uri n g th e 
O pti miz ati o n  
p eri o d, s o a 
w e ekl y p h o n e 
call is n ot 
n ec ess ary as 
l o n g as t h e 
s u bj ect is s e e n 
i n offic e 
N o n e  
I nf or m e d 
C o ns e nt  
 
 
 
 
 
4. 0/ 0 6J A N 2 0 2 3  
C h a n g e d 
R a n d o miz ati o
n a n d I n Cli nic 
T esti n g 
wi n d o w t o 
all o w f or 
o v erl a p wit h 4 
w e ek visit  
All o ws f or 
s u bj ect t o 
c o m bi n e 4 
w e ek 
O pti miz ati o n 
a n d 
R a n d o miz ati o n 
a n d i n Cli nic 
T esti n g w h e n 
st a bl e o n 
t h er a py at t h e 
discr eti o n of 
t h e PI 
N o n e  
n o n e  
 
 
 
 
 

E v al u ati o n of L o n g -t er m P ati e nt E x p eri e n c e wit h a 
M e dtr o ni c Cl o s e d -L o o p S C S S y st e m ( Cl o s e d -L o o p S C S s tu d y )  
 
 
Cli ni c al I n v e sti g ati o n Pl a n  
0 6 J A N 2 0 2 3 
V er si o n 4 . 0 
P a g e 1 1 7 of 1 1 7  
 
 
 
 
 
V ersi o n  
S u m m ar y of 
ch a n g es  
J ustific ati o n of 
c h a n g es 
P ot e nti al 
i m p act of 
t h e c h a n g e 
o n 
p erf or m a nc
e, 
eff ecti v e n e
ss, or s af et y 
or ot h er 
e n d p oi nts  
I d e ntific ati o n 
of t h e 
aff ect e d 
st u d y 
d oc u m e nts  
A ut h or(s)/ Titl e  
4. 0/ 0 6J A N 2 0 2 3  
R e m ov e d D oi  
r ef er e nc es i n 
t h e R ef er e nc e 
T a bl e  
D oi n u m b ers 
w er e i nc orr ect  
N o n e  
N o n e