Description of Relugolix Use in Patients With Prostate Cancer: An Analysis of National Veterans Affairs Health Care Network Data
Conditions: Prostate Cancer
Sponsor: Pfizer

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 of 4 1
St u d y i nf or m ati o n
Title
Descri pti o n of Rel u g oli x Use i n Patie nts wit h Pr ostate Ca ncer: A n 
A nal y sis of Nati o nal Vetera ns Affairs Healt h Care Net w or k Data
Pr ot oc ol n u m ber
C 4 7 5 1 0 0 9
Pr ot oc ol versi o n 
i de ntifier
Versi o n 1. 0
D ate
0 6 Ma y
2 0 2 4
Acti ve s u bst a nce
Rel u g oli x ( A T C c o de: L 0 2 B X 0 4 ) 
Me dici n al pr o d uct
Or g o v y x
Rese arc h q uesti o n 
a n d o bjecti ves
T his st u d y  ai ms t o ac hie ve t he f oll o wi n g o bjecti ves:

P ri mar y o bjecti ve:
1.
T o descri be de m o gra p hic s a n d cli nical c haracteristics of
patie nts wit h pr ostate ca ncer ( P C) w h o i nitiate d rel u g oli x 

E x pl orat or y o bjecti ve s:
2.
T o assess treat me nt patter ns a m o n g patie nts wit h P C w h o 
i nitiate d rel u g oli x
3.
T o esti mate a d here nce a n d persiste nce wit h 
rel u g oli x 
a m o n g patie nts wit h P C w h o i nitiate d rel u g oli x
4.
T o assess test oster o ne s u p pressi o n a n d pr ostate -s pecific 
a nti ge n res p o nses a m o n g a n dr o ge n de pri vati o n t hera py 
(A D T ) naï ve patie nts wit h P C w h o i nitiate d rel u g oli x
5.
T o descri be a n d c o m pare de m o gra p hics a n d cli nical 
c haracteristics bet wee n Blac k a n d n o n -His pa nic W hite 
patie nts wit h P C w h o i nitiate d rel u g oli x
6.
T o descri be a n d c o m pare ti me t o treat me nt c ha n ges 
bet wee n Blac k a n d n o n -His pa nic W hite patie nts wit h P C 
w h o i nitiate d rel u g oli x 
7.
T o esti mate a n d c o m pare a d here nce a n d persiste nce wit h 
rel u g oli x bet wee n Blac k a n d n o n- His pa nic W hite
patie nts 
wit h P C w h o i nitiate d rel u g oli x
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 of 4 1
A ut h or
 P har m D M S
T his d oc u me nt c o ntai ns c o nfi de ntial i nf or mati o n bel o n gi n g t o Pfizer.  E xce pt as ot her w ise a gree d t o i n 
writi n g, b y acce pti n g or re vie wi n g t his d oc u me nt, y o u a gree t o h ol d t his i nf or mati o n i n c o nfi de nce a n d n ot 
c o p y or discl ose it t o ot hers (e xce pt w here re q uire d b y a p plica ble la w) or use it f or u na ut h orize d p ur p oses.  
I n t he e ve nt of a n y act ual or s us pecte d breac h of t his o bli gati o n, Pfizer m ust be pr o m ptl y n otifie d.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)
P P D
P P D

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 of 4 1
1. C O N T E N T S
1. C O N T E N T S ...........................................................................................................................3
2. LI S T O F A B B R E VI A T I O N S................................................................................................5
3. R E S P O N SI B L E P A R TI E S ....................................................................................................7
4. A B S T R A C T ...........................................................................................................................8
5. A M E N D M E N T S A N D U P D A T E S .....................................................................................1 1
6. MI L E S T O N E S .....................................................................................................................1 2
7. R A TI O N A L E A N D B A C K G R O U N D ................................................................................1 3
8. R E S E A R C H Q U E S TI O N A N D O BJ E C TI V E S .................................................................1 5
9. R E S E A R C H M E T H O D S................................ ....................................................................1 7
9. 1. St u d y  desi g n............................................................................................................1 7
9. 2. Setti n g ......................................................................................................................1 7
9. 2. 1. I ncl usi o n criteria .........................................................................................1 7
9. 2. 2. E xcl usi o n criteria ........................................................................................1 7
9. 3. Varia bles ..................................................................................................................1 8
9. 4. Data s o urces ............................................................................................................2 4
9. 5. St u d y size ................................................................................................................2 4
9. 6. Data ma na ge me nt ....................................................................................................2 4
9. 7. Data a nal y sis ...........................................................................................................2 4
9. 7. 1. Data a nal y sis f or Objecti ve 1: T o descri be de m o gra p hics a n d cli nical 
c haracteristics of patie nts wit h P C w h o i nitiate d rel u g oli x ............................. 2 4
9. 7. 2. Data a nal y sis f or O bjecti ve 2: T o assess treat me nt patter ns a m o n g 
patie nts wit h P C w h o i nitiate d rel u g oli x................................ ..........................2 5
9. 7. 3. Data a nal y sis f or O bjecti ve 3: T o esti mate a d here nce a n d persiste nce 
wi t h rel u g oli x a m o n g patie nts wit h P C w h o i nitiate d rel u g oli x......................2 6
9. 7. 4. Data a nal y sis f or O bjecti ve 4: T o assess test oster o ne s u p pressi o n a n d 
P S A res p o nses a m o n g A D T naï ve patie nts wit h P C w h o i nitiate d rel u g oli x ..2 6
9. 7. 5. Data a nal y sis f or Objecti ve 5: T o descri be a n d c o m pare de m o gra p hics 
a n d cli nical c haracteristics bet wee n Blac k a n d n o n- His pa nic W hite patie nts 
wit h P C w h o i nitiate d rel u g oli x................................ .......................................2 6
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 4 of 4 1
9. 7. 6. Data a nal y sis f or O bjecti ve 6: T o descri be a n d c o m pare ti me t o 
treat me nt c ha n ges bet wee n Blac k a n d n o n- His pa nic W hite patie nts wit h P C 
w h o i nitiate d rel u g oli x .....................................................................................2 7
9. 7. 7. Data a nal y sis f or O bjecti ve 7: T o esti mate a n d c o m pare a d here nce a n d 
persiste nce wit h rel u g oli x bet wee n Blac k a n d n o n - His pa nic W hite patie nts 
wit h P C w h o i nitiate d rel u g oli x................................ .......................................2 7
9. 8. Q ualit y  c o ntr ol.........................................................................................................2 7
9. 9. L i mitati o ns of t he researc h met h o ds .......................................................................2 7
9. 1 0. Ot her as pects .........................................................................................................2 8
1 0. P R O T E C TI O N O F H U M A N S U BJ E C T S ........................................................................2 9
1 0. 1. Patie nt i nf or mati o n................................ ................................................................2 9
1 0 . 2. Patie nt c o nse nt.......................................................................................................2 9
1 0. 3. I nstit uti o nal re vie w b oar d (I R B)/I n de pe n de nt et hics c o m mittee (I E C) ................2 9
1 0. 4. Et hical c o n d uct of t he st u d y ..................................................................................2 9
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S ......................................................................................................................3 0
1 2. P L A N S F O R DI S S E M I NA TI N G A N D C O M M U NI C A TI N G S T U D Y R E S U L T S ........3 1
1 3. LI S T O F T A B L E S .............................................................................................................3 2
1 4. LI S T O F FI G U R E S ...........................................................................................................3 3
A N N E X 1. LI S T O F S T A N D -A L O N E D O C U M E N T S .........................................................3 4
A N N E X 2. A D DI TI O N A L  I N F O R M A TI O N.........................................................................3 5
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 5 of 4 1
2. LI S T O F A B B R E VI A TI O N S
A b bre vi ati o n
Defi niti o n
A C S
A merica n Ca ncer S ociet y
A D T
A n dr o ge n De pri vati o n T hera p y
A R PI
A n dr o ge n Rece pt or Pat h wa y  In hi bit or
A T C
A nat o mical T hera pe utic C he mical
C A
Calif or nia
C CI
C harls o n C o m or bi dit y  In de x
C D C
Ce nters f or Disease C o ntr ol a n d Pre ve nti o n
C D W
C or p orate Data Ware h o use
CI R C L
Ce nter f or I nte grate d Researc h i n Ca ncer a n d 
Lifest y le
C P T
C urre nt Pr oce d ural Ter mi n ol o g y
d L
Deciliter
D OI
Di gital O bject I de ntifier
F D A
F o o d a n d Dr u g A d mi nistrati o n
G n R H
G o na d otr o pi n -Releasi n g H or m o ne
G PI
Ge neric Pr o d uct I de ntifier
H C P C S
Healt hcare C o m m o n Pr oce d ure C o di n g S ys te m
I C D
I nter nati o nal Classificati o n of Diseases
I C D- 9-C M
I nter nati o nal Classificati o n of Diseases, 9 t h Re visi o n, 
Cli nical M o dificati o n
I C D- 1 0-C M
I nter nati o nal Classificati o n of Diseases, 1 0t h Re visi o n, 
Cli nical M o dificati o n
I C D- 1 0-P C S
I nter nati o nal Classificati o n of Diseases, 1 0t h Re visi o n,
Pr oce d ures
I E C
I n de pe n de nt Et hics C o m mittee
I RB
I nstit uti o nal R e vie w B oar d
L H R H
L utei nizi n g H or m o ne – releasi n g H or m o ne
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 6 of 4 1
M A
Massac h usetts
M P R
Me dicati o n Pr ocessi n g Rati o
N A A C C R
N ort h A merica n Ass ociati o n of Ce ntral Ca ncer 
Re gistries
N C
N ort h Car oli na
N C C N
Nati o nal C o m pre he nsi ve Ca ncer Net w or k
N CI
Nati o nal Ca ncer I nstit ute
n g
Na n o gra m
N H T
N o vel H or m o nal T hera p y 
NJ
Ne w Jerse y
N S A A
N o n - Ster oi dal A nti-A n dr o ge n
N Y
Ne w Y or k
N Y C
Ne w Y or k Cit y
P A S S
P ost - A ut h orizati o n Safet y St u dy
P C
Pr ostate Ca ncer
P D C
Pr o p orti o n of Da y s C o vere d
P H
Pr o p orti o nal Hazar ds
P M CI D
P u b Me d Ce ntral I de ntifier
P MI D
P u b Me d I de ntifier 
P S A
Pr ostate -S pecific A nti ge n
S M D
Sta n dar dize d Mea n Differe nce
S M P A
S u mit o m o P har ma A merica, I nc
U S
U nite d States
V A
Vetera ns Affairs
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 7 of 4 1
3. R E S P O N SI B L E P A R TI E S
Pri nci p al I n vesti g at or (s) of t he Pr ot oc ol
N a me, de gree(s)
J o b Title
Affili ati o n
A d dress
A g nes 
H o n g, 
P har m D 
M S
Direct or, Val ue & E vi de nce 
U S, Pr ostate Ca ncer
Patie nt & Healt h I m pact –
O nc ol o g y
Pfizer I nc.
6 6 H u ds o n Bl v d , 
H u ds o n Yar ds, 
N Y C , N Y
J ua n F. 
Raz o
Se ni or Ma na ger, U S 
Me dical Affairs, Pr ostate 
Ca ncer
Pfizer I nc.
6 6 H u ds o n Bl v d , 
H u ds o n Yar ds, 
N Y C , N Y
Sc ott 
Fla n ders
E xec uti ve Direct or, Me dical 
Affairs Strate g y
S u mit o m o 
P har ma 
A merica, I nc 
( S M P A)
8 4 Waterf or d Dr, 
Marl b or o u g h, M A
Be n Li
Direct or, Statistics Lea d
Pfizer I nc.
1 0 0 2 0 6 N ort h, 
Pea pac k, NJ
Ste p he n 
Free dla n d , 
M D
Pr ofess or , Ur ol o g y ;
Ass ociate Direct or,
E d ucati o n & Trai ni n g ;
Direct or, Ce nter f or 
I nte grate d Researc h i n 
Ca ncer a n d L ifestyl e 
( CIR C L) ;
Warsc ha w, R o berts o n, La w 
Fa milies C hair i n Pr ostate 
Ca ncer
Ce dars -Si nai
Ce dars -Si nai, 
Ur ol o g y  - T hir d, 
8 6 3 5 W T hir d St 
# 1 0 7 0 W, L os 
A n geles, C A, 
9 0 0 4 8
Ra na 
Mc ka y , 
M D
Me dical O nc ol o gist ;
Ass ociate Pr ofess or of 
Me dici ne
U ni versit y  of 
Calif or nia Sa n 
Die g o Healt h
9 4 0 0 Ca m p us 
P oi nt Dr
Sa n Die g o, C A 
9 2 0 3 7
H o n g b o Ya n g, 
P h D
Ma na gi n g Pri nci pal
A nal y sis 
Gr o u p, I nc.
1 1 1 H u nti n gt o n 
A ve
1 4 t h Fl o or
B ost o n, M A 0 2 1 9 9
Wei Ga o, P h D
Vice Presi de nt
A nal y sis 
Gr o u p, I nc.
1 1 1 H u nti n gt o n 
A ve
1 4 t h Fl o or
B ost o n, M A 0 2 1 9 9
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 8 of 4 1
4. A B S T R A C T
Title: Descri pti o n of Rel u g oli x Use i n Patie nts wit h Pr ostate Ca ncer: A n A nal y sis of Nati o nal 
Vetera ns Affairs Healt h Care Net w or k Data
Versi o n: 1. 0
D ate of Pr ot oc ol: 6 M a y
2 0 2 4
A ut h or: 
R ati o n ale a n d B ac k gr o u n d: Pr ostate ca ncer ( P C) is t he m ost c o m m o n ca ncer a n d t he sec o n d 
lea di n g ca use of ca ncer deat h a m o n g me n i n t he U nite d States. A n dr o ge n de pri vati o n t hera p y 
( A D T) s uc h as i njecta ble l utei nizi n g h or m o ne –releasi n g h or m o ne ( L H R H) a g o nists (e. g., 
le u pr oli de) is t he sta n dar d of care f or P C patie nts. A D T treat me nt ca n s u p press test oster o ne 
le vel t o castrate le vel a n d dela y  the pr o gressi o n of t he disease. H o we ver, L H R H a g o nist ca n 
ca use a n i nitial s ur ge of test oster o ne w hic h res ults i n a flare of s y m pt o ms i ncl u di n g b o ne pai n 
or o bstr ucti ve uri nar y  sy m pt o ms. I n ad diti o n, L H R H a g o nist ca n i ncrease t he ris k of 
car di o vasc ular e ve nts. As a n alter nati ve t o L H R H, g o na d otr o pi n -releasi n g h or m o ne ( G n R H) 
a nta g o nist ca n be c o nsi dere d. Rel u g oli x is a rece ntl y ap pr o ve d o ral G n R H a nta g o nist, w hic h 
ca n ra pi dly s u p press test oster o ne le vel wit h o ut t he i nitial s ur ge. T he p hase 3 H E R O trial of 
rel u g oli x i n a d va nce d P C patie nts has c o m pare d t he efficac y a n d safet y of oral rel u g oli x wit h 
le u pr oli de a n d f o u n d t hat rel u g oli x ca n achie ve castrati o n q uic ker a n d ca n better mai ntai n 
castrati o n t ha n le u pr oli de. I n a d diti o n, t he i nci de nce of maj or a d verse car di o vasc ular e ve nts i n 
t he H E R O trial was
l o wer f or rel u g oli x t ha n le u pr oli de ( 2. 9 % vs. 6. 2 %). A d diti o nall y , 
treat me nt was ass ociate d wit h a m ore ra pi d ti me t o test oster o ne rec o ver y . T he p ositi ve res ults 
ha ve le d t o t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) a p pr o val of rel u g oli x i n Dece m ber 2 0 2 0
f or t he treat me nt of a d ults wit h a d va nce d P C . C urre ntl y, rel u g oli x is t he o nl y  AD T o pti o n 
a vaila ble i n oral f or m, disti n g uis hi n g fr o m t he tra diti o nal i njecta ble L H R H a g o nists. T here are 
se veral st u dies i n ot her disease s ha ve s h o w n t hat patie nts ha ve a prefere nce f or oral 
me dicati o ns d ue t o c ult ural c o nsi derati o ns, a p pre he nsi o n t o war ds i njecti o ns a n d nee dles, a n d 
c o ncer ns re gar di n g i nc orrect a d mi nistrati o n . W hile t he i ntr o d ucti o n of rel u g oli x has offere d a 
u ni q ue o p p ort u nit y  for patie nts wit h P C, it's vital t o u n dersta n d h o w it is bei n g use d i n real-
w orl d. H o we ver, fe w st u dies ha ve i n vesti gate d t his as pect. 
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)
P P D

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 9 of 4 1
O bjecti ves: T his st u d y  ai ms t o ac hie ve t he f oll o wi n g o bjecti ves:

Pri mar y  O bjecti ve: 
1.
T o descri be de m o gra p hic s a n d cli nical c haracteristics of patie nts wit h P C w h o i nitiate d 
rel u g oli x 

E x pl orat or y  o bjecti ves:
2.
T o assess treat me nt patter ns a m o n g patie nts wit h P C w h o i nitiate d rel u g oli x
3.
T o esti mate a d here nce a n d persiste nce wit h rel u g oli x a m o n g patie nts wit h P C w h o 
i nitiate d rel u g oli x
4.
T o assess test oster o ne s u p pressi o n a n d pr ostate -s pecific a nti ge n ( P S A) res p o nses
a m o n g A D T naï ve patie nts wit h P C w h o i nitiate d rel u g oli x
5.
T o descri be a n d c o m pare de m o gra p hics a n d cli nical c haracteristics bet wee n Blac k a n d 
n o n -His pa nic W hite patie nts wit h P C w h o i nitiate d rel u g oli x
6.
T o descri be a n d c o m pare ti me t o treat me nt c ha n ges bet wee n Blac k a n d n o n -His pa nic 
W hite patie nts wit h P C w h o i nitiate d rel u g oli x
7.
T o esti mate a n d c o m pare a d here nce a n d persiste nce wit h rel u g oli x bet wee n Blac k a n d 
n o n -His pa nic W hite patie nts wit h P C w h o i niti ate d rel u g oli x
St u d y Desi g n:
T he c urre nt st u d y will be a retr os pecti ve data a nal ys is t o descri be patie nt 
c haracteristics , treat me nt patter ns , a d here nce, a n d persiste nce a m o n g patie nts wit h P C w h o 
i nitiate d rel u g oli x. A d ult (a ge d ≥1 8 y ears) male patie nts wit h P C w h o h a d rel u g oli x (i nitiati o n 
date as t he i n de x date) will be selecte d fr o m t he Nati o nal Vetera ns Affairs ( V A) Healt h Care 
Net w or k data base s. Patie nts will be re q uire d t o ha ve c o nti n u o us eli gi bilit y f or at least 3 6 5 d a y s
pri or t o t he i n de x date a n d 9 0 d a y s after t he i n de x date ( u nless die d wit hi n 9 0 d a y s). T he 
baseli ne peri o d will be t he 3 6 5 da ys pri or t o t he i n de x date. T he f oll o w -u p peri o d will be fr o m 
t he i n de x date t o t he earliest of deat h, e n d of c o nti n u o us eli gi bilit y  or e n d of data a vaila bilit y.
P o p ul ati o n: T he o verall p o p ulati o n will i ncl u de P C patie nts w h o i nitiate d rel u g oli x. T he f oll o wi n g 
sa m ple selecti o n criteria will be use d: 

I ncl usi o n criteria 
o
Male wit h ≥ 1 dia g n osis f or P C
o
Ha d ≥ 2 prescri pti o ns of rel u g oli x o n or after t he first o bser ve d P C dia g n osis . T he 
i de ntificati o n peri o d f or rel u g oli x use will be fr o m Dece m ber 1 8, 2 0 2 0 t o Dece m ber 
3 1 , 2 0 2 3
-
I n de x date: t he i nitiati o n date of rel u g oli x
o
At least 1 8 years ol d at t he i n de x date
o
Ha d c o nti n u o us acti vit y in t he data f or at least 3 6 5 da y s bef ore t he i n de x date a n d 9 0 
da y s f oll o wi n g t he i n de x date ( u nless die d wit hi n 9 0 da y s) 

E xcl usi o n criteria:  
o
Ha d s ur gical castrati o n ( bilateral orc hiect o m y ) a n y ti me bef ore t he i n de x date
o
Partici pate d i n cli nical trials wit hi n 3 0 da y s pri or t o or 9 0 da ys after t he i n de x date
o
Ha d a n y ot her pri mar y ca ncer (e xcl u di n g n o n- mela n o ma s ki n ca ncer) d uri n g t he 
baseli ne peri o d
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 0 of 4 1
V ari a bles: B aseli ne de m o gra p hic s a n d cli nical c haracteristics will i ncl u de varia bles s uc h as a ge, 
race/et h nicit y, ge o gra p hic re gi o ns, i n de x ye ar, pre vi o us treat me nt, C harls o n C o m or bi dit y 
In de x sc ore, a n d baseli ne c o m or bi dities. O utc o mes will i ncl u de treat me nt patter ns , a d here nce ,
a n d persiste nce wit h rel u g oli x, a n d testoster o ne a n d P S A res p o nses (if sa m ple sizes all o w).
D at a S o urces: Ja n uar y 1, 2 00 6 t o Dece m ber 3 1 , 2 0 2 3 d ata fr o m t he Nati o nal V A Healt h Care 
Net w or k will be use d.
St u d y Size: All eli gi ble patie nts a vaila ble f or t he a nal ys is will be i ncl u de d.
D at a A n al ysis: Descri pti ve a nal ys is will be c o n d uct e d f or baseli ne de m o gra p hic s a n d cli nical 
c haracteristics, a n d a d here nce/ persiste nce t o rel u g oli x. Mea ns, sta n dar d de viati o ns, me dia ns, 
a n d i nter q uartile ra n ge will be esti mate d f or c o nti n u o us varia bles. C o u nts a n d perce nta ges will 
be esti mate d f or cate g orical varia bles. T reat me nt se q ue nce will be descri be d usi n g a Sa n ke y  
dia gra m. Ka pla n -Meier a nal ysis will be use d t o descri be ti me t o treat me nt c ha n ges. A d here nce 
t o rel u g oli x will be calc ulate d usi n g me dicati o n pr ocessi n g rati o ( M P R) a n d pr o p orti o n of d a y s 
c o vere d (P D C ). Persiste nce wit h rel u g oli x will be a nal yz e d usi n g Ka pla n -Meier a nal ys is. If 
sa m ple sizes are a de q uate, t he c o u nts a n d perce nta ges of patie nts w h o ha d test oster o ne a n d 
P S A
res p o nses will 
be 
s u m marize d.
U na dj uste d 
a n d 
a dj uste d 
c o m paris o ns 
of 
a d here nce/ persiste nce t o rel u g oli x a n d ti me t o treat me nt c ha n ges bet wee n Blac k a n d n o n-
His pa nic W hite patie nts will be c o n d ucte d usi n g a p pr o priate statistical m o dels .
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 1 of 4 1
5. A M E N D M E N T S A N D U P D A T E S
N o ne .
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 2 of 4 1
6. MI L E S T O N E S
Milest o ne
Pl a n ne d d ate
A p pr o val of t he Nati o nal Vetera ns Affairs ( V A)
Healt h Care Net w or k data a p plicati o n
N o ve m ber 3 0, 2 0 2 3
Fi nalize Pr ot oc ol
Ma y  0 6, 2 0 2 4
Fi nal st u d y  re p ort
Ma y  3 1, 2 0 2 5
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 3 of 4 1
7. R A TI O N A L E A N D B A C K G R O U N D
Pr ostate ca ncer ( P C) is t he m ost c o m m o n ca ncer a n d t he sec o n d lea di n g ca use of ca ncer deat h 
a m o n g me n i n t he U nite d States. 1 T he Nati o nal Ca ncer I nstit ute ( N CI) esti mate d 2 9 9, 0 1 0 ne w 
cases a n d 3 5, 2 5 0 deat hs of P C i n 2 0 2 4. 2 W hile t he l o n g-ter m o utl o o k is p ositi ve f or earl y-sta ge 
P C, s ur vi val rates drasticall y  decrease o nce t he disease has s prea d be yo n d t he pr ostate gla n d (i.e., 
bec o mi n g metastatic) or w he n t he disease bec o mes castrati o n -resista nt.2
A n dr o ge n de pri vati o n t hera p y ( A D T) is t he sta n dar d of care f or patie nts wit h P C , i ncl u di n g s uc h 
as i njecta ble l utei nizi n g h or m o ne – releasi n g h or m o ne ( L H R H) a g o nists (e. g., le u pr oli de) a n d 
g o na d otr o pi n -releasi n g h or m o ne ( G n R H) a nta g o nist . A D T treat me nt ca n s u p press test oster o ne 
le vel t o castrate le vel a n d dela y  the pr o gressi o n of t he disease. L H R H a g o nist use ca n ca use a n 
i nitial s ur ge of test oster o ne w hic h res ults i n a flare of s ym pt o ms i ncl u di n g b o ne pai n or o bstr ucti ve 
uri nar y  sy m pt o ms. I n a d diti o n, L H R H a g o nist is ass ociate d wit h 
a n i ncrease d ris k of 
car di o vasc ular e ve nts. 3 As a n alter nati ve t o L H R H, G n R H a nta g o nist ca n be c o nsi dere d, w hic h 
d oes n ot ca use t he i nitial s ur ge i n test oster o ne le vel . 
Rel u g oli x is a rece ntl y  ap pr o ve d G n R H a nta g o nist, w hic h ca n ra pi dl y s u p press test oster o ne le vel 
wit h o ut t he i nitial s ur ge. T he p hase 3 H E R O
trial of rel u g oli x i n a d va nce d P C patie nts has 
c o m pare d t he efficac y a nd safety o f oral rel u g oli x wit h le u pr oli de a n d has f o u n d t hat rel u g oli x ca n 
ac hie ve castrati o n q uic ker a n d ca n better mai ntai n castrati o n t ha n le u pr oli de.4 I n ad diti o n, t he 
i nci de nce of maj or a d verse car di o vasc ular e ve nts i n t he H E R O trial was als o l o wer f or rel u g oli x 
t ha n le u pr oli de ( 2. 9 % vs. 6. 2 %). 4 T he p ositi ve res ults ha ve le d t o t he F o o d a n d Dr u g 
A d mi nistrati o n ( F D A) a p pr o val of rel u g oli x i n Dec e m ber 2 0 2 0. 5
Rel u g oli x is t he o nl y  A D T o pti o n a vaila ble i n oral f or m, disti n g uis hi n g fr o m t he tra diti o nal 
i njecta ble L H R H a g o nists.6 W hile ma n y  fact ors c o ul d i nfl ue nce patie nts' treat me nt prefere nces, a 
                                                
1 A merica n Ca ncer S ociet y ( A C S), t he Ce nters f or Disease C o ntr ol a n d Pre ve nti o n ( C D C), t he N ort h A merica n 
Ass ociati o n 
of Ce ntral Ca ncer Re gistries ( N A A C C R), a n d t he N CI . A n n ual 
Re p ort t o t he Nati o n 
2 0 2 2 . 
htt ps://seer.ca ncer. g o v/re p ort _t o _ nati o n . Accesse d o n Ma y 1 , 2 0 2 3.
2 N CI . Ca ncer Stat Facts: Pr ostate Ca ncer. htt ps://seer.ca ncer. g o v/statfacts/ ht ml/ pr ost. ht ml . Accesse d o n M a y  1, 
2 0 2 3.
3 Da ve y P, Ale xa n dr o u K. Assess me nt a n d miti gati o n of car di o vasc ular ris k f or pr ostate ca ncer patie nts: a 
re vie w of t he e vi de nce. I nter nati o nal J o ur nal of Cli nical Practice. 2 0 2 2 Ma y 1 7; 2 0 2 2.
4 S h ore N D, Saa d F, C o o ks o n M S, Ge or ge DJ, Saltzstei n D R, T utr o ne R, A kaza H, B ossi A, va n Vee n h u yze n 
D F, Sel b y B, Fa n X. Oral rel u g oli x f or a n dr o ge n -de pri vati o n t hera p y i n a d va nce d pr ostate ca ncer. Ne w  E n gla n d 
J o ur nal of Me dici ne. 2 0 2 0 J u n 4; 3 8 2( 2 3): 2 1 8 7- 96.
5 T he U nite d States F o o d a n d Dr u g A d mi nistrati o n. F D A a p pr o ves rel u g oli x f or a d va nce d pr ostate ca ncer. 
htt ps:// w w w.f da. g o v/ dr u gs/res o urces -i nf or mati o n-a p pr o ve d -dr u gs/f da -a p pr o ves-rel u g oli x-a d va nce d -pr ostate -
ca ncer #: ~:te xt = O n % 2 0 Dece m ber % 2 0 1 8 % 2 C % 2 0 2 0 2 0 % 2 C % 2 0t he, patie nts % 2 0 wit h % 2 0a d va nc e d % 2 0 pr ostate % 2 0
ca ncer . Accesse d o n A u g ust 2 4, 2 0 2 3.
6 C or des L M, Karzai F, Fi g g W D, Ma da n R A. Rel u g oli x i n Cli nical Practice: T he Best R o ute f or All? 
O nc ol o gist. 2 0 2 3 A u g 3; 2 8( 8): 6 4 7 -6 5 0. d oi: 1 0. 1 0 9 3/ o nc ol o/ o ya d 0 9 9. P MI D: 3 7 1 6 2 4 9 7; P M CI D: P M C 1 0 4 0 0 1 3 1.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 4 of 4 1
fe w st u dies i n ot her diseases ha ve s h o w n patie nts ha ve a str o n g prefere nce f or oral me dicati o ns 
d ue t o c ult ural c o nsi derati o ns, a p pre he nsi o n t o war ds i njecti o ns a n d nee dles, a n d c o ncer ns 
re gar di n g i nc orrect a d mi nistrati o n.7, 8 M ore o ver, as n ote d fr o m t he H E R O trial, t here are ot her 
p ote ntial be nefits t o rel u g oli x s uc h as ra pi d test oster o ne le vel decli ne a n d i m pr o ve d test oster o ne 
rec o ver y wit h p ote ntial f or miti gati o n of maj or a d verse car di o vasc ular e ve nts. As s uc h, a s a n 
effecti ve oral treat me nt, rel u g oli x ca n p ote ntiall y hel p a d dress a n u n met nee d i n P C .
W hile t he i ntr o d ucti o n of rel u g oli x has offere d a u ni q ue o p p ort u nit y f or patie nts wit h P C , it’s 
vital t o u n dersta n d treat me nt patter ns a n d t he co m bi nati o n use of rel u g oli x wit h ot her c o m m o nl y 
e m pl o ye d dr u gs i n P C treat me nt . H o we ver, fe w st u dies ha ve l o o ke d i nt o t his as pect. O ur st u dy 
ai ms t o bri d ge t his ga p b y e val uati n g real -w orl d treat me nt patter ns i n v ol vi n g rel u g oli x t o 
u n dersta n d h o w it is bei n g use d i n real -w orl d, i ncl u di n g w het her it is use d as m o n ot hera p y or 
c o m bi nati o n t hera p y, a d here nce, persiste nce , a n d p ote ntiall y treat me nt res p o nse. 
T his pr ot oc ol is n ot desi g nate d as a p ost -a ut h orizati o n safety st u d y p er C T 3 4 P ost -A ut h orizati o n 
Safet y  St u dies ( P A S S), n or is it a c o m mit me nt or re q uire me nt t o a n y re g ulat or y a ut h orit y.6
                                                
7 B o y e, K., R oss, M., M o d y, R., K o ni g, M., & Gel h or n, H. ( 2 0 2 1). Patie nts' prefere nces f or o nce -dail y oral 
vers us o nce -wee kl y i njecta ble dia betes me dicati o ns: T he R E VI S E st u d y. Di a betes, o besity & met a b olis m , 2 3 ( 2), 
5 0 8 – 5 1 9. htt ps:// d oi. or g/ 1 0. 1 1 1 1/ d o m. 1 4 2 4 4
8 Fa ya d F, Zia de N R, Mer he b G, Att o ui S, Ai k o A, Mr o ue K, Masri A F. Patie nt prefere nces f or r he u mat oi d 
art hritis treat me nts: res ults fr o m t he nati o nal cr oss -secti o nal L E R A C S st u d y. Patie nt Prefer A d here nce. 2 0 1 8 A u g 
3 1; 1 2: 1 6 1 9 -1 6 2 5. d oi: 1 0. 2 1 4 7/ P P A. S 1 6 8 7 3 8. P MI D: 3 0 2 1 4 1 6 4; P M CI D: P M C 6 1 2 4 8 0 3.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 5 of 4 1
8. R E S E A R C H Q U E S TI O N A N D O B J E C TI V E S
Usi n g data fr o m t he Nati o nal V A Healt h Care Net w or k data base s, t he st u d y will retr os pecti vel y 
a nal yz e data t o descri be patie nt c haracteristics a n d t he treat me nt patter ns of rel u g oli x a m o n g 
patie nts wit h P C w h o i nitiate d rel u g oli x. 
T a ble 1 . O bjecti ves a n d e n d p oi nts
O bjecti ves
E n d p oi nts
1.
( Pri mar y) T o descri be de m o gra p hics a n d 
cli nical c haracteristics of patie nts wit h P C 
w h o i nitiate d rel u g oli x

Patie nt b aseli ne de m o gra p hics a n d 
cli nical c haracteristics 
2.
(E x pl orat or y ) T o assess treat me nt patter ns 
a m o n g patie nts wit h P C w h o i nitiate d 
rel u g oli x

In de x treat me nt re gi me n distri b uti o n

Treat me nt se q ue nce prese nte d b y  Sa n ke y 
dia gra m

Ti me t o treat me nt c ha n ges b y  Ka pla n-
Meier a nal y sis
3.
(E x pl orat or y ) T o esti mate a d here nce a n d 
persiste nce wit h rel u g oli x a m o n g patie nts 
wit h P C w h o i nitiate d rel u g oli x

A d here nce t o rel u g oli x defi ne d b y 
me dicati o n pr ocessi n g rati o (M P R )

A d here nce t o rel u g oli x defi ne d b y 
pr o p orti o n of da ys c o vere d (P D C )

Persiste nce wit h rel u g oli x b y  Kapla n -
Meier a nal y sis
4.
( E x pl orat or y) T o assess test oster o ne 
s u p pressi o n a n d pr ostate -s pecific a nti ge n 
(P S A ) res p o nses a m o n g A D T naï ve 
patie nts wit h P C w h o i nitiate d rel u g oli x

Test oster o ne s u p pressi o n

P S A res p o nse
5.
( E x pl orat or y) T o descri be a n d c o m pare 
de m o gra p hics a n d cli nical c haracteristics 
bet wee n Blac k a n d n o n -His pa nic W hite 
patie nts wit h P C w h o i nitiate d rel u g oli x

Patie nt baseli ne de m o gra p hics a n d 
cli nical c haracteristics b y race
6.
( E x pl orat or y) T o descri be a n d c o m pare 
ti me to treat me nt c ha n ges bet wee n Blac k 
a n d n o n -His pa nic W hite patie nts wit h P C 
w h o i nitiate d rel u g oli x

Ti me t o treat me nt c ha n ges b y  Ka pla n-
Meier a nal y sis b y  race
7.
( E x pl orat or y) T o esti mate a n d c o m pare 
a d here nce a n d persiste nce wit h rel u g oli x 
bet wee n Blac k a n d n o n- His pa nic W hite
patie nts wit h P C w h o i nitiate d rel u g oli x

A d here nce t o rel u g oli x defi ne d b y M P R 
b y  race

A d here nce t o rel u g oli x defi ne d b y P D C
b y  race

Persiste nce wit h rel u g oli x b y  Ka pla n-
Meier a nal y sis b y  race
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 6 of 4 1
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 7 of 4 1
9. R E S E A R C H M E T H O D S 
9. 1. St u d y d esi g n
T his is a retr os pecti ve, o bser vati o nal st u dy usi n g Ja n uar y 1, 2 0 0 6 – Dece m ber 3 1 , 2 0 2 3 data fr o m 
t he Nati o nal V A
Healt h Care Net w or k data bases . P C patie nts w h o i nitiate d rel u g oli x will be 
selecte d base d o n dia g n osis c o des, a ge, treat me nt recei ve d, a n d c o nti n u o us acti vit y in t he healt h 
care net w or k . T he i de ntificati o n peri o d f or rel u g oli x use will be fr o m Dece m ber 1 8, 2 0 2 0 t o
Dece m ber 3 1, 2 0 2 3. Dece m ber 1 8, 2 0 2 0 is t he a p pr o val date f or rel u g oli x i n t he U S, a n d Dece m ber
3 1 , 2 0 2 3 is t he e n d of a vaila ble data. T he i nde x date will be defi ne d as t he i nitiati o n date of 
rel u g oli x. T he baseli ne peri o d will be 3 6 5 da y s pri or t o t he i n de x date ( he nce t he start of t he st u dy 
peri o d is Dece m ber 1 8, 2 0 1 9). T he f oll o w-u p peri o d will be fr o m t he i n de x date t o t he earliest of 
deat h , e n d of c o nti n u o us eli gi bilit y or e n d of data a vaila bilit y. M ost of t he p atie nt c haracteristics 
will be descri be d d uri n g t he baseli ne peri o d. Certai n patie nt c haracteristics will be descri be d usi n g 
all data a vaila ble pri or t o t he i n de x date ( i.e., data pri or t o Dece m ber 1 8, 2 0 1 9 will als o be use d if 
a vaila ble; see m ore details i n Ta ble 2). Treat me nt patter ns, a d here nce , a n d persiste nce wit h 
rel u g oli x, a n d P S A a n d test oster o ne res p o nses (if sa m ple size all o ws) will be assesse d d uri n g t he 
f oll o w-u p peri o d.
9. 2. Setti n g
T he Nati o nal V A Healt h Care Net w or k data will be use d f or t he c urre nt a nal y sis. P C patie nts 
i nitiate d rel u g oli x will be selecte d f or a nalys is base d o n i ncl usi o n a n d e xcl usi o n criteria bel o w. 
9. 2. 1. I ncl usi o n criteri a
Patie nts w h o met all of t he f oll o wi n g sa m ple selecti o n criteria will be i ncl u de d:

Male wit h ≥1 dia g n osis of P C (I nter nati o nal Classificati o n of Diseases, 1 0t h Re visi o n, 
Cli nical M o dificati o n [IC D - 1 0-C M] C 6 1 )

Ha d ≥2 prescri pti o ns of rel u g oli x o n or after t he first o bser ve d P C d ia g n osis. T he i nitiati o n 
date of rel u g oli x will be selecte d as t he i n de x d ate

At least ≥1 8 y ears ol d as of t he i n de x date

Ha d c o nti n u o us acti vit y i n t he data f or ≥3 6 5 da y s pri or t o t he i n de x date a n d ≥9 0 da y s
si nce t he i n de x date ( u nless die d wit hi n 9 0 da ys). T he b aseli ne peri o d will be defi ne d as 
t he 3 6 5- d a y peri o d pri or t o t he i n de x date . T he f oll o w-u p peri o d will be fr o m t he i n de x 
date t o t he e n d of c o nti n u o us eli gi bilit y , data a vaila bilit y, or deat h, w hic he ver ha p pe ne d 
first
9. 2. 2. E xcl usi o n criteri a
Patie nts will n ot be i ncl u de d fr o m t he st u d y if t he y:

Ha d s ur gical castrati o n ( bilateral orc hiect o m y ) a n y ti me bef ore t he i n de x date
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4 -WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 8 of 4 1

Ha d e vi de nce of cli nical trial partici pati o n wit hi n 3 0 da y s pri or t o t he i n de x date or 
wit hi n 9 0 da y s si nce t he i n de x date

Ha d a n y ot her pri mar y  ca ncer (e xcl u di n g n o n -mela n o ma s ki n ca ncer) d uri n g t he baseli ne 
peri o d
Fi g ure 1 . S a m ple selecti o n f or P C p atie nts i niti ate d rel u g oli x
9. 3. V ari a bles
Baseli ne varia bles (Ta ble 2) will be meas ure d d uri n g t he baseli ne peri o d (3 6 5 da y s pri or t o t he 
i n de x date ). Treat me nt patter n s, a d here nce a n d persiste nce, a n d cli nical varia bles (Ta ble 3 ) will be 
meas ure d d uri n g t he f oll o w -u p peri o d.
T a ble 2 . B aseli ne de m o gr a p hic a n d cli nic al c h ar acteristic v ari a bles
V ari a ble
O per ati o n al defi niti o n
A ge
A ge will be defi ne d as of t he i n de x date a n d retai ne d i n 
t he dataset as a c o nti n u o us varia ble a n d a cate g orical 
varia ble (e. g., ≤5 9, 6 0 -6 9, 7 0 -7 9, ≥8 0 y ears ol d).
R ace /et h nicit y
Pr o p orti o n of patie nts t hat were n o n -His pa nic W hite, 
Blac k, His pa nic, ot her o r u n k n o w n will be s u m marize d .
Ge o gr a p hic regi o ns
Pr o p orti o n of patie nts t hat li ve d i n N ort heast, Mi d west, 
S o ut h a n d West
areas will be s u m marize d .
I n de x y e ar
A cate g orical v aria ble f or t he i n de x cale n dar ye ar will be 
s u m marize d.
Site of met ast asis
Pr o p orti o n of patie nts t hat ha d a metastatic dia g n osis at 
t he f oll o wi n g sites: b o ne o nl y, b o ne a n d n o de o nly, n o de 
F oll o w -u p peri o d
Fr o m t he i n de x date t o t he e n d of c o nti n u o us 
eli gi bilit y, data a vaila bilit y or deat h, w hic he ver 
ha p pe ne d first
B aseli ne

Dia g n osis of P C fr o m 
Ja n uar y 1, 2 00 6 t o 
Dece m ber 3 1 , 2 0 2 3

Male
B aseli ne peri o d
3 6 5 da ys of c o nti n u o us eli gi bilit y
 
I n de x d ate

I nitiati o n of rel u g oli x o n or after t he 
first o bser ve d P C dia g n osis a n d 
wit hi n Dece m ber 1 8 , 2 0 20 -
Dece m ber 3 1 , 2 0 2 3

≥ 1 8 years ol d
P ost -i n de x 

Ha d a n ot her fill of rel u g oli x

≥ 9 0 da ys of c o nti n u o us 
eli gi bilit y
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 1 9 of 4 1
V ari a ble
O per ati o n al defi niti o n
o nl y , viscera a n d ot her, will be s u m marize d a m o n g 
patie nts wit h metastatic P C. A ll data a vaila ble pri or t o t he 
i n de x date will be use d.
Tre a t me nt h ist or y
Pr o p orti o n of patie nts w h o ha d eac h of t he f oll o wi n g 
treat me nts i n t he baseli ne peri o d will be e val uate d: 

P r ostatect o m y

C hr o nic oral c ortic oster oi d use

P ai n me dicati o n ( o pi oi ds)

A D T treat me nt (le u pr oli de, de gareli x, gosereli n , 
h istreli n, tri pt oreli n)

A n dr o ge n rece pt or p at h wa y in hi bit or (A R PI ;
a birater o ne, a pal uta mi de, dar ol uta mi de, 
e nzal uta mi de)

N o n -ster oi dal anti -an dr o ge n (N S A A ; bical uta mi de, 
nil uta mi de, fl uta mi de)

C he m ot hera p y ( d oceta xel, ca bazita xel, car b o plati n, 
o xali plati n, cis plati n, mit o xa ntr o ne)

I m m u n ot hera py (s i p ule ucel- T, pe m br oliz u ma b)

Ra di u m 2 2 3

S y ste mic ket oc o naz ole

O la pari b

R uca pari b

Talaz o pari b

Nira pari b

L uteti u m L u 1 7 7 vi pi v oti de tetra xeta n

Ra di ot hera p y 
T reat me nts c o nsi dere d as a part of i n de x treat me nt 
re gi me n will n ot be fla g ge d as baseli ne treat me nts if 
recei ve d wit hi n 3 0 da ys pri or t o i n de x date.
Ti me fr o m first o bser ve d P C 
di a g n osis d ate t o t he i nde x d ate
Ti me fr o m t he first o bser ve d P C date i n t he data t o t he 
i n de x date will be e val uate d. All data a vaila ble pri or t o t he 
i n de x date will be use d.
N CI 
C h arls o n 
C o m or bi dit y 
I n de x ( C CI) sc ore
T he N CI versi o n of t he C CI  sc ore will be create d d uri n g 
t he baseli ne peri o d.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 0 of 4 1
V ari a ble
O per ati o n al defi niti o n
C o m or bi dities
A bi nar y  varia ble ( yes/ n o) will be create d f or patie nts wit h 
a dia g n osis of eac h of t he f oll o wi n g c o m or bi dities d uri n g 
t he baseli ne peri o d:

H y perte nsi o n

H y perli pi de mia

Dia betes

Uri nar y  tract i nfecti o n

C hr o nic o bstr ucti ve p ul m o nar y  disease

Arr h yt h mia

C o n gesti ve heart fail ure

M y ocar dial i nfarcti o n

Str o ke

A n gi na pect oris

I nfla m mat or y b o wel disease

Ac ute c or o nar y  sy n dr o me

Se x ual d y sf u ncti o n

D e pressi o n

A n xiet y

H ot flas hes

C o g niti ve i m pair me nt

Maj or a d verse car di o vsca ular e ve nt ( defi ne d b y  
a n y e vi de nce of car di o m yo pat h y , heart fail ure, 
isc he mic heart disease, m y ocar dial i nfarcti o n, 
p ul m o nar y  e m b olis m, or str o ke )
P S A
Baseli ne P S A val ue ( a m o n g a vaila ble) base d o n t he P S A 
val ue cl osest t o t he i n de x date d uri n g t he 9 0 -d a y  wi n d o w 
( or 1 8 0 -d a y , t o be fi nalize d base d o n t he n u m ber of 
patie nts wit h n o n- missi n g P S A val ue i n t hese ti me fra mes )
o n or pri or t o t he i n de x date will be e val uate d.
Test oster o ne
Baseli ne test oster o ne val ue ( a m o n g a vaila ble) base d o n
test oster o ne val ue cl osest t o t he i n de x date d uri n g t he 9 0 -
da y  wi n d o w ( or 1 8 0- d a y ; will be c o nsiste nt wit h t he ti me 
wi n d o w f or baseli ne P S A ) o n or pri or t o t he i n de x date
will be e val uate d .
Met ast atic 
vs. n o n -met ast atic 
P C
A bi nar y  varia ble f or patie nts wit h metastatic vs. n o n-
metastatic P C will be create d. Metastatic P C will be 
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 1 of 4 1
V ari a ble
O per ati o n al defi niti o n
defi ne d as ha vi n g e vi de nce of meta stasis d uri n g t he 
baseli ne peri o d or wit hi n 9 0 da y s si nce t he i n de x date.
A D T n aï ve vs. A D T 
e x perie nce d 
A bi nar y  varia ble f or patie nts w h o were A D T naï ve vs.
A D T e x perie nce d will be create d. A D T naï ve will be 
defi ne d as ha vi n g n o rec or ds of a n y s yste mic A D T 
treat me nt e ver base d o n all a vaila ble data pri or t o t he 
i n de x date (i.e., i ncl u di n g baseli ne peri o d data a n d a n y  
a vaila ble data pri or t o t he baseli ne peri o d) . Sys te mic A D T 
treat me nt i ncl u des L H R H a g o nists a n d G n R H a nta g o nists 
(i.e., de gareli x, rel u g oli x, g osereli n, histreli n, le u pr oli de, 
tri pt oreli n)
T a ble 3 . T re at me nt p atter n s, a d here nce, persiste nce, a n d cli nic al v ari a bles d uri n g t he 
f oll o w-u p peri o d
V ari a ble
O per ati o n al defi niti o n
I n de x tre at me nt 
I n de x treat me nt re gi me ns i ncl u de:

Rel u g oli x m o n ot hera p y

Rel u g oli x + N S A A o nl y  (at least 9 0 da ys of N S A A 
use)

Rel u g oli x + A R PI  +/- N S A A ( n o c he m ot hera p y)

Rel u g oli x + A R PI  + c he m ot hera p y

Rel u g oli x + c he m ot hera p y +/ - N S A A ( n o A R PI)

Rel u g oli x + ot her ( n o A R PI , n o c he m ot hera p y)
I n de x treat me nt re gi me n will be defi ne d base d o n 
treat me nts recei ve d wit hi n 3 0 da ys bef ore t he i n de x date 
a n d wit hi n 9 0 da ys after t he i n de x date.
S pecific treat me nts i ncl u de d i n eac h treat me nt cate g or y  
(i.e., A D T, N S A A, A R PI, c he m ot hera py, i m m u n ot hera p y ) 
are descri be d i n “ Treat me nt hist or y ” i n Ta ble 2 . Ot her 
treat me nts i ncl u de i m m u n ot hera py, ra di u m 2 2 3, ola pari b, 
r uca pari b, talaz o pari b, nira pari b a n d l uteti u m Lu 1 7 7 
vi pi v oti de tetra xeta n.
N u m ber of patie nts w h o recei ve d a ny ra di ot hera p y d uri n g 
t he i n de x treat me nt will be s u m marize d.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 2 of 4 1
V ari a ble
O per ati o n al defi niti o n
Tre at me nt p atter ns of 
rel u g oli x
Treat me nt patter ns of rel u g oli x i ncl u de:

C o nti n ue d rel u g oli x as i n t he i n de x treat me nt 
(re gar dless of disc o nti n uati o n of c o nc o mita nt 
me dicati o ns) 

C o nti n ue d rel u g oli x wit h a ne w a d d - o n sys te mic 
P C treat me nt (e xcl u di n g A D T)

Disc o nti n ue d rel u g oli x a n d s witc he d t o a n ot her 
A D T treat me nt

Disc o nti n ue d rel u g oli x wit h o ut s witc hi n g t o 
a n ot her A D T treat me nt
A d d -o n s y ste mic P C treat me nts i ncl u de:

A R PI

N S A A 

C he m ot hera p y 

I m m u n ot hera py 

Ra di u m 2 2 3

Ket oc o naz ole

Ola pari b

R uca pari b

Talaz o pari b 

Nira pari b

L uteti u m L u 1 7 7 vi pi v oti de tetra xeta n
A d d -o n t hera p y will be e val uate d fr o m 9 0 da ys after t he 
i n de x peri o d t o t he e n d of t he f oll o w-u p peri o d . 
Ti me t o tre at me nt c h a n ges
T he ti me t o treat me nt c ha n ges of i nterest i ncl u de:

Ti me t o disc o nti n uati o n of rel u g oli x 

Ti me t o s witc hi n g t o a differe nt A D T treat me nt

Ti me t o a d d a ne w s ys te mic P C treat me nt t o 
rel u g oli x
Tre at me nt a d here nce
A d here nce t o rel u g oli x p ost t he i n de x date will be 
descri be d usi n g b ot h M P R a n d P D C :

M P R: S u m of t he da y s of s u p pl y di vi de d b y t he 
n u m ber of da y s bet wee n t he first fill a n d t he e n d of 
t he last refill (i.e., i ncl u di n g t he d a y s of s u p pl y 
fr o m t he last refill) 

P D C: S u m of t he n o n- o verla p pi n g (i.e., n ot d o u ble 
c o u nti n g of o verla ps) d a y s of s u p pl y c o vere d 
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 3 of 4 1
V ari a ble
O per ati o n al defi niti o n
di vi de d b y  a pre-deter mi ne d peri o d f oll o wi n g 
treat me nt i nitiati o n (e. g., 6 a n d 1 2 m o nt hs)
A d here nce will be descri be d as a c o nti n u o us varia ble a n d 
as a bi nar y varia ble (< 0. 8 0: n o n -a d here nt , ≥0. 8 0: 
a d here nt )
Tre at me nt persiste nce
Persiste nce t o rel u g oli x will be descri be d as t he pr o p orti o n 
of patie nts w h o di d n ot disc o nti n ue rel u g oli x (i.e., wit h a 
treat me nt ga p, s witc h t o a n ot her A D T, or deat h; t he 
mi ni m u m da y s of treat me nt ga p, e. g., 4 5 or 6 0 d a y s, will 
be fi nalize d base d o n sa m ple size a n d cli nical i n p ut)
d uri n g t he f oll o w- u p peri o d . Treat me nt ga ps will be
assesse d fr o m t he e n d of t he da ys of s u p ply of t he 
pre vi o us prescri pti o n t o t he earliest of t he ne xt 
prescri pti o n or t he e n d of data a vaila bilit y . 
P S A res p o nse
O nl y  if sa m ple size is s ufficie nt a n d a m o n g patie nts wit h 
at least o ne baseli ne a n d o ne f oll o w- u p peri o d P S A 
meas ure : 

T he n u m ber a n d p erce nta ge of patie nts wit h ≥5 0 %
a n d ≥9 0 % decli ne fr o m t he baseli ne P S A t o a ny 
P S A meas ure me nt d uri n g t he f oll o w-u p peri o d a n d 
w hile o n rel u g oli x

T he n u m ber a n d perce nta ge of patie nts wit h t he 
na dir P S A val ue d uri n g t he f oll o w -u p peri o d a n d 
o n treat me nt of rel u g oli x < 0. 0 1 , 0. 1, a n d 0. 2
n g/ m L
Test oster o ne res p o nse 
O nl y  if sa m ple size is s ufficie nt a n d a m o n g patie nts wit h 
at least o ne f oll o w- u p peri o d test oster o ne meas ure:

T he n u m ber a n d perce nta ge of patie nts wit h at 
least o ne test oster o ne val ue of < 5 0 n g / d L a n d < 2 0 
n g/ d L d uri n g t he f oll o w- u p peri o d a n d w hile o n 
rel u g oli x
If sa m ple size is s ufficie nt, t he a nalys is a b o ve ma y be 
c o n d ucte d a m o n g patie nts wit h at least o ne baseli ne a n d 
o ne f oll o w -u p peri o d test oster o ne meas ure
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 4 of 4 1
9. 4. D at a s o urces
Ja n uar y 1, 2 00 6 t o Dece m ber 3 1 , 2 0 2 3 data fr o m t he Nati o nal V A Healt h Care Net w or k will be 
use d f or t his st u d y . T his net w or k is t he U S’s lar gest i nte grate d healt h care s yste m wit h o ver 
1, 7 0 0 sites of care, ser vi n g a p pr o xi matel y  8. 7 6 milli o n vetera ns eac h ye ar. T he V A Healt h 
S y ste m C or p orate Data Ware h o use ( C D W) i ncl u des all me dical e nc o u nter i nf or mati o n i n t he 
V A, c o m prise d of me dical ce nters, c o m m u nit y -base d o ut patie nt cli nics, c o m m u nit y -li vi n g 
ce nters, vetera n ce nters, a n d d o miciliaries. T he V A C D W st ores data i n se parate data bases, o ne 
f or eac h ty pe of cli nical i nf or mati o n - i n patie nt me dicati o n, i n patie nt la b orat or y, i n patie nt 
a d missi o n, o ut patie nt me dicati o n, o ut patie nt la b orat or y, o ut patie nt visits, etc. T he data bases 
pr o vi de de m o gra p hic i nf or mati o n a n d c o ntai n c o m pre he nsi ve ser vices, i ncl u di n g pri mar y  care, 
s pecialt y care, i n patie nt care, re ha bilitati o n, l o n g-ter m care, h o me care, a n d ot her ser vices, t o 
militar y  vetera ns. T he data base als o i ncl u des date of deat h. T he date of deat h is e xtracte d fr o m 
t he V A electr o nic healt h rec or d s ys te ms a n d verifie d b y official s o urces, i ncl u di n g V A facilities, 
deat h certificates, a n d Nati o nal Ce meter y  A d mi nistrati o n. Inf or mati o n o n C D W, i ncl u di n g date 
of deat h, is u p date d o n a dail y  base. Ca use of deat h is n ot a vaila ble o n C D W.
9. 5. St u d y size
As n o pri ori h y p ot heses are s pecifie d, sa m ple size calc ulati o ns are n ot a p plica ble. T he n u m ber of 
patie nts eli gi ble f or t he st u d y will be deter mi ne d i n acc or da nce wit h t he sa m ple selecti o n 
c o n d ucte d per t he criteria descri be d i n Secti o n 9 . 2.
9. 6. D at a m a n a ge me nt 
A clea n, patie nt -le vel dataset will be ge nerate d f or use t hr o u g h o ut t he st u d y. T his pr ocess will 
e ntail basic e x pl orat or y c hec ks t o e ns ure data i nte grity;  clea ni n g a n d ref or matti n g t he ra w data as 
nee de d; a n d creati n g varia bles f or all ke y  st u d y meas ures, i ncl u di n g patie nt c haracteristics, 
treat me nt start a n d e n d dates, a n d classificati o n of treat me nts a n d me dicati o n . All data will be 
st ore d a n d mai ntai ne d o n a sec ure e ncr ypte d n o n -cl o u d-base d ser ver a n d accesse d o ver a sec ure 
i nter nal pri vate wi de area net w or k. T he data will be ma de accessi b le o nl y t o i n di vi d uals w or ki n g 
o n t he c urre nt st u d y . N o atte m pt will be ma de t o i de ntif y i n di vi d ual patie nts, h os pitals, or 
p h y sicia ns. A nalys es will be c o n d ucte d usi n g S A S 9. 4 ( S A S I nstit ute, Car y  N C).
9. 7. D at a a n al ysis
9. 7. 1. D at a a n al ysis f or O bjecti ve 1: T o descri be de m o gr a p hics a n d cli nic al c h ar acteristics 
of p atie nts wit h P C w h o i niti ate d rel u g oli x
Descri pti ve a nal ys is will be c o n d ucte d f or baseli ne de m o gra p hic s a n d cli nical c haracteristics .
Mea ns , sta n dar d de viati o ns, me dia ns, a n d i nter q uartile ra n ge w ill be esti mate d f or c o nti n u o us 
varia bles. C o u nts a n d perce nta ges will be esti mate d f or cate g orical varia bles. If t he sa m ple sizes
all o w, sta n dar dize d mea n differe nce ( S M D) will be calc ulate d t o c o m pare t he patie nt baseli ne 
c haracteristics bet wee n metastatic vs. n o n -metastatic P C c o h orts . F or eac h varia ble, t he S M D 
will be calc ulate d as t he differe nce i n mea n bet wee n t w o c o h orts di vi de d b y t he sta n dar d 
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4 -WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 5 of 4 1
de viati o n of t he t w o c o h orts p o ole d t o get her. T he a bs ol ute val ue of a S M D > 1 0 % will be 
c o nsi dere d as a n i n dicat or f or si g nifica nt i m bala nce.
9. 7. 2. D at a a n al ysis f or O bjecti ve 2: T o assess tre at me nt p atter ns a m o n g p atie nts wit h P C 
w h o i niti ate d rel u g oli x
9. 7. 2. 1. In de x tre at me nt distri b uti o n
T he distri b uti o n of t he i n de x treat me nt will be descri be d usi n g c o u nts a n d perce nta ges . I n de x 
treat me nt will be defi ne d base d o n treat me nts recei ve d wit hi n 3 0 da ys bef ore t he i n de x date a n d 
wit hi n 9 0 da y s after t he i n de x date.
9. 7. 2. 2. T re at me nt p atter ns of rel u g oli x 
Treat me nt patter ns of rel u g oli x will be a nal y ze d a n d prese nte d usi n g S a n ke y dia gra ms (see a n 
e xa m ple i n Fi g ure 2). T he f o ur treat me nt patter ns descri be d i n Ta ble 3 will be c o nsi dere d. T he 
n u m ber a n d pr o p orti o n of patie nts wit h eac h of t he f o ur treat me nt patter ns will be s u m marize d.
Fi g ure 2 . E x a m ple of a S a n ke y di a gr a m (f or ill ustr ati o n p ur p ose)
9. 7. 2. 3. T i me t o tre at me nt c h a n ges 
Ka pla n -Meier a nal y sis will be c o n d ucte d t o descri be t he f oll o wi n g ti me-t o-e ve nt o utc o mes f or 
t he treat me nt patter ns as liste d i n Ta ble 3 :
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 6 of 4 1

Ti me t o disc o nti n uati o n of rel u g oli x 

Ti me t o s witc hi n g t o a differe nt A D T treat me nt

Ti me t o a d d a ne w s ys te mic P C treat me nt t o rel u g oli x
T he n u m ber a n d pr o p orti o n of patie nts wit h t he c orres p o n di n g e ve nt will be pl otte d o ver ti me 
a n d t he n u m ber at ris k ta ble o ver ti me will be prese nte d. T he me dia n ti me t o e ve nt will be 
calc ulate d.
9. 7. 3. D at a a n al ysis f or O bjecti ve 3: T o esti m ate a d here nce a n d persiste nce wit h rel u g oli x 
a m o n g p atie nts wit h P C w h o i niti ate d rel u g oli x
A d here nce t o rel u g oli x as defi ne d i n Ta ble 3 will be descri be d. M P R will be s u m marize d o ver t he 
e ntire e x p os ure t o rel u g oli x d uri n g t he f oll o w- u p peri o d. P D C will be s u m marize d wit hi n t he 6 , 
1 2, a n d 1 8 m o nt h s (te ntati vel y, pe n di n g o n t he fi nal le n gt h of f oll o w-u p) si nce t he i n de x date .
Mea ns, sta n dar d de viati o ns, me dia ns, a n d i nter q uartile ra n ge will be esti mate d f or a d here nce as a 
c o nti n u o us varia ble . C o u nts a n d perce nta ges will be esti mate d f or a d here nce as a bi nar y  varia ble.
Patie nts will be re q uire d t o ha ve c o m plete f oll o w- u p data d uri n g t he ti me t o be i ncl u de d i n eac h 
a d here nce calc ulati o n.
Persiste nce t o rel u g oli x as defi ne d i n Ta ble 3 will be descri be d usi n g Ka pla n -Meier a nal ys is 
si nce t he i n de x date. T he n u m ber a n d pr o p orti o n of patie nts persiste nt t o rel u g oli x will be pl otte d 
o ver ti me a n d t he n u m ber at ris k ta ble o ver t i me will be prese nte d. 
9. 7. 4. D at a a n al ysis f or O bjecti ve 4 : T o assess test oster o ne s u p pressi o n a n d P S A res p o nses
a m o n g A D T n aï ve p atie nts wit h P C w h o i niti ate d rel u g oli x
If sa m ple size is s ufficie nt, t he c o u nt a n d perce nta ge of patie nts wit h test oster o ne res p o nses as 
defi ne d i n Ta ble 3 will be calc ulate d a m o n g A D T naï ve patie nts wit h at least o ne test oster o ne 
meas ure d uri n g t he f oll o w-u p peri o d. Si milarl y , if sa m ple size is s ufficie nt, t he c o u nt a n d 
perce nta ge of patie nts w it h P S A res p o nses as defi ne d i n Ta ble 3 will be calc ulate d a m o n g A D T 
naï ve patie nts wit h at least o ne baseli ne a n d o ne f oll o w -u p peri o d P S A meas ure .
9. 7. 5. D at a a n al ysis f or O bjecti ve 5 : T o descri be a n d c o m p are de m o gr a p hics a n d cli nic al 
c h ar acteristics bet wee n Bl ac k a n d n o n -His p a nic W hite p atie nts wit h P C w h o i niti ate d 
rel u g oli x
T he sa me descri pti ve a nal ysis descri be d i n Secti o n 9. 7. 1 will be c o n d ucte d i n Blac k a n d n o n -
His pa nic W hite patie nts se paratel y . If t he sa m ple sizes all o w, S M D will be calc ulate d t o c o m pare 
t he patie nt baseli ne c haracteristics bet wee n Blac k vs. n o n -His pa nic W hite c o h orts . A d diti o nall y , 
p - val ues fr o m a p pr o priate statistical tests (e. g., t-tests or ra n k -s u m tests f or c o nti n u o us varia bles 
a n d c hi-s q uare tests f or cate g orical varia bles) c o m pari n g Blac k vs. n o n-His pa nic W hite c o h orts 
will be re p orte d.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 7 of 4 1
9. 7. 6. D at a a n al ysis f or O bjecti ve 6: T o descri be a n d c o m p are ti me t o tre at me nt c h a n ges 
bet wee n Bl ac k a n d n o n -His p a nic W hite p atie nts wit h P C w h o i niti ate d rel u g oli x
T he sa me descri pti ve a nal yses descri be d i n Secti o n 9. 7. 2. 3 will be c o n d ucte d i n Bac k a n d n o n-
His pa nic W hite patie nts se paratel y. U na dj uste d a n d a dj uste d c o m paris o ns bet wee n t he t w o race 
gr o u ps will be c o n d ucte d. C o x pr o p orti o nal hazar ds ( P H ) re gressi o ns will be use d t o c o m pare t he 
ti me t o treat me nt c ha n ges bet wee n t he t w o race gr o u ps. Patie nt c haracteristics t o be i ncl u de d i n 
t he a dj uste d m o dels will be selecte d base d o n fi n di n gs i n Secti o n 9. 7. 5 a n d cli nical i n p ut.
9. 7. 7. D at a a n al ysis f or O bjecti ve 7: T o esti m ate a n d c o m p are a d here nce a n d persiste nce 
wit h rel u g oli x bet wee n Bl ac k a n d n o n -His p a nic W hite p atie nts wit h P C w h o i niti ate d 
rel u g oli x
T he sa me descr i pti ve a nal yses descri be d i n Secti o n 9. 7. 3 will be c o n d ucte d i n Bac k a n d n o n-
His pa nic W hite patie nts se paratel y. U na dj uste d a n d a dj uste d c o m paris o ns bet wee n t he t w o race 
gr o u ps will be c o n d ucte d. Ge neralize d li near m o dels will be use d t o c o m pare ad here nce t o 
rel u g oli x bet wee n t he t w o race gr o u ps. C o x P H re gressi o ns will be use d t o c o m pare persiste nce
bet wee n t he t w o race gr o u ps. Patie nt c haracteristics t o be i ncl u de d i n t he a dj uste d m o dels will be 
selecte d base d o n fi n di n gs i n Secti o n 9. 7. 5 a n d cli nical i n p ut.
9. 8. Q u alit y co ntr ol
Best practice g ui deli nes will be f oll o we d t o e ns ure pr oject q ualit y, i ncl u di n g str uct ure d 
or ga nizati o n of pr oject materials (e. g., data e xtracts, statistical s oft ware pr o gra ms, o ut p ut ta bles) 
a n d sta n dar d i nter nal a u dit pr ocess. T he a u dit pr ocess b ot h c o n fir ms t he vali dit y of t he a nal ytical 
a p pr oac h a n d e ns ures t hat all pr o gra ms a n d res ults are acc urate.
9. 9. Li mit ati o ns of t he rese arc h met h o ds
T he a nal ys es c o n d ucte d as part of t his st u d y  are s u bject t o t he f oll o wi n g li mitati o ns, w hic h will 
be a d dresse d i n a n y write -u p of t he st u d y:

As t his st u d y  will be c o n d ucte d a m o n g v etera ns, its fi n di n gs ma y n ot be ge neraliza ble t o
ot her p o p ulati o ns 

Certai n ass u m pti o ns will be ma de i n or der t o de pict treat me nt patter ns . H o we ver, t he 
defi niti o n of treat me nt patter ns will ne vert heless be s u bject t o ass u m pti o ns t hat ma y  n ot 
matc h u p t o t he prescri bi n g p h ys icia ns’ i nte nt

Data are s u bject t o i nacc uracies i n c o di n g of dia g n oses. T he prese nce of a dia g n osis c o de 
i n t he data d oes n ot necessaril y mea n t he prese nce of disease. T he disease ma y be 
i nc orrectl y c o de d, or t he c o de was i ncl u de d as a r ule -o ut criteri o n

T he prese nce of a prescri pti o n d oes n ot necessaril y mea n t he me dicati o n was c o ns u me d 
as prescri be d. I n a d diti o n, prescri pti o ns fille d o ver t he c o u nter or pr o vi de d as sa m ples b y 
t he p h ysicia n are n ot i ncl u de d i n t he data
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 8 of 4 1

T he fact t hat o ur e ntr y  criteria is at least 2 s u bscri pti o ns of rel u g oli x mea ns we are 
selectin g patie nts w h o were a ble t o t olerate t he first m o nt h a n d f oll o we d u p t o recei ve a 
sec o n d m o nt h. H o w t his c o h ort relates t o all patie nts gi ve n rel u g oli x is u n k n o w n.
9. 1 0. Ot her as pects
N ot a p plica ble .
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 2 9 of 4 1
1 0. P R O T E C TI O N O F H U M A N S U B J E C T S
T his st u d y  i n v ol ves data t hat e xist i n a n o n ymize d str uct ure d f or mat a n d c o ntai n n o patie nt 
pers o nal i nf or mati o n.  
1 0. 1. P atie nt i nf or m ati o n 
T his st u d y  i n v ol ves data t hat e xist i n a n o n ymize d str uct ure d f or mat a n d c o ntai n n o patie nt 
pers o nal i nf or mati o n . 
1 0. 2. P atie nt c o nse nt
As t his st u d y  i n v ol ves a n o n ymize d str uct ure d data, w hic h acc or di n g t o a p plica ble le gal 
re q uire me nts d o n ot c o ntai n data s u bject t o pri vac y la ws, o btai ni n g i nf or me d c o nse nt fr o m 
patie nts b y  Pfizer is n ot re q uire d.  
1 0. 3. I nstit uti o n al re vie w b o ar d (I R B)/I n de pe n de nt et hics c o m mittee (I E C)
A n I R B wai ver was recei ve d.
1 0. 4. Et hic al c o n d uct of t he s t u d y
T he st u d y will be c o n d ucte d i n acc or da nce wit h le gal a n d re g ulat or y re q uire me nts, as well as wit h 
scie ntific p ur p ose, val ue a n d ri g or a n d f oll o w ge nerall y acce pte d researc h practices descri be d i n 
G ui deli nes f or G o o d P har mac oe pi de mi ol o g y  Practices iss ue d b y  the I nter nati o nal S ociet y  for 
P har mac oe pi de mi ol o g y .
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 0 of 4 1
1 1. M A N A G E M E N T A N D R E P O R TI N G O F A D V E R S E E V E N T S/ A D V E R S E 
R E A C TI O N S 
T his is a retr os pecti ve a nal ysis usi n g an o n y mize d Nati o nal V A Healt h Care Net w or k data base . I n 
t he data, i n di vi d ual patie nt data are n ot retrie ve d or vali date d, a n d it is n ot p ossi ble t o li n k (i.e., 
i de ntif y a pote ntial ass ociati o n bet wee n) a partic ular pr o d uct a n d me dical e ve nt f or a n y i n di vi d u al. 
T h us, t he mi ni m u m criteria f or re p orti n g a n a d verse e ve nt (i.e., i de ntifia ble patie nt, i de ntifia ble 
re p orter, a s us pect pr o d uct, a n d e ve nt) ca n n ot be met.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 1 of 4 1
1 2. P L A N S F O R DI S S E MI N A T I N G A N D C O M M U NI C A TI NG S T U D Y R E S U L T S
I n t he e ve nt of a ny pr o hi biti o n or restri cti o n i m p ose d (e. g., cli nical h ol d) b y a n a p plica ble 
c o m pete nt a ut h orit y i n a n y area of t he w orl d, or if t he i n vesti gat or is a ware of a n y ne w 
i nf or mati o n w hic h mi g ht i nfl ue nce t he e val uati o n of t he be nefits a n d ris ks of a Pfizer pr o d uct, 
Pfizer s h o ul d be i nf or me d i m me diatel y.  
  
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 2 of 4 1
1 3. LI S T O F T A B L E S 
Ta ble 1. O bjecti ves a n d e n d p oi nts ...........................................................................................1 5
Ta ble 2. Baseli ne de m o gra p hic a n d cli nical c haracteristic varia bles ......................................1 8
Ta ble 3. Treat me nt patter ns, a d here nce, persiste nce, a n d cli nical varia bles d uri n g t he 
f oll o w-u p peri o d ...................................................................................................2 1
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 3 of 4 1
1 4. LI S T O F FI G U R E S
Fi g ure 1. Sa m ple selecti o n f or P C patie nts i nitiate d rel u g oli x................................ ................1 8
Fi g ure 2. E xa m ple of a Sa n ke y  dia gra m (f or ill ustrati o n p ur p ose)..........................................2 5
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-
A u g -2 0 2 3  
Pa ge 3 4 of 4 1
A N N E X 1. LI S T O F S T A N D -A L O N E D O C U M E N T S
N o ne.
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 3 5 of 4 1
A N N E X 2. A D DI TI O N A L I N F O R M A TI O N
A p pe n di x T a ble 1 . C o des f or P C tre at me nts
G PI
H C P C S/ C P T
I C D
A D T
Orc hiect o m y
C P T
I C D-1 0 -C M
5 4 5 2 0, 5 4 5 2 2, 5 4 5 3 0, 5 4 5 3 5, 
5 4 6 9 0
Z 9 0. 7 9
I C D-1 0 -P C S
0 V 5 9 0 Z Z, 0 V 5 9 3 Z Z, 0 V 5 9 4 Z Z, 
0 V 5 B 0 Z Z, 0 V 5 B 3 Z Z, 0 V 5 B 4 Z Z, 
0 V 5 C 0 Z Z, 0 V 5 C 3 Z Z, 0 V 5 C 4 Z Z, 
0 V T 9 0 Z Z, 0 V T 9 4 Z Z, 0 V T B 0 Z Z, 
0 V T B 4 Z Z, 0 V T C 0 Z Z, 0 V T C 4 Z Z
L H R H a g o nists/a nta g o nists
De gareli x
2 1 4 0 5 5 2 5 1 0
J 9 1 5 5
G osereli n
2 1 4 0 5 0 0 5
J 9 2 0 2
Histreli n
2 1 4 0 5 0 0 7 1 0
J 1 6 7 5, J 9 2 2 5, J 9 2 2 6, S 0 1 3 3
Le u pr oli de
2 1 4 0 5 0 1 0
J 1 9 5 0, J 9 2 1 7, J 9 2 1 8, J 9 2 1 9, 
Q 0 0 5 7
Rel u g oli x
2 1 4 0 5 5 7 0 0 0 0 3 2 0, 2 4 9 9 3 5 0 3 8 0 0 3 2 0
Tri pt oreli n
2 1 4 0 5 0 5 0
J 3 3 1 5
A R PI
A pal uta mi de
2 1 4 0 2 4 1 0 0 0
A birater o ne
2 1 4 0 6 0 1 0 2 0
Dar ol uta mi de
2 1 4 0 2 4 2 5 0 0
E nzal uta mi de
2 1 4 0 2 4 3 0 0 0
N S A A
Bical uta mi de
2 1 4 0 2 4 2 0 0 0
Fl uta mi de
2 1 4 0 2 4 4 0 0 0
Nil uta mi de
2 1 4 0 2 4 6 0 0 0
C he m ot hera p y
H C P C S
I C D
Ca bazita xel
2 1 5 0 0 0 0 3 0 0
C 9 2 7 6, J 9 0 4 3
D oceta xel
2 1 5 0 0 0 0 5 0 0
J 9 1 7 0, J 9 1 7 1
Car b o plati n
2 1 1 0 0 0 1 5 0 0
J 8 5 3 0, J 9 0 7 0, J 9 0 8 0, J 9 0 9 0, 
J 9 0 9 1, J 9 0 9 2, J 9 0 9 3, J 9 0 9 4, 
J 9 0 9 5, J 9 0 9 6, J 9 0 9 7
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 3 6 of 4 1
Cis plati n
2 1 1 0 0 0 2 0 0 0
J 9 0 4 5
O xali plati n
2 1 1 0 0 0 2 8 0 0
J 9 2 6 3
Mit o xa ntr o ne 
2 1 2 0 0 0 5 5 0 0
J 9 2 9 3
I m m u n ot hera p y
H C P C S
I C D
Si p ule ucel -T
2 1 6 5 1 0 7 0 0 0
Q 2 0 4 3, C 9 2 7 3
Pe m br oliz u ma b
2 1 3 5 7 9 5 3 0 0 2
J 9 2 7 1, C 9 0 2 7
Ot hers 
H C P C S
I C D
Ra di u m -2 2 3
2 1 6 0 0 0 5 5 0 0
A 9 6 0 6
Ket oc o naz ole
1 1 4 0 4 0 4 0 0 0, 9 6 3 0 1 0 6 4 0 0, 9 0 1 5 4 0 4 5 0 0
Ola pari b
2 1 5 3 5 5 6 0
L uteti u m L u 1 7 7 vi pi v oti de tetra xeta n
2 1 6 0 0 0 4 5 8 0 2 0 2 0
A 9 6 0 7
Nira pari b
2 1 5 3 5 5 5 0 2 0 0, 2 1 4 0 9 9 0 2 1 2 0
Talaz o pari b
2 1 5 3 5 5 8 0 4 0 0 1
Nira pari b
2 1 5 3 5 5 5 0 2 0 0, 2 1 4 0 9 9 0 2 1 2 0
R uca pari b
2 1 5 3 5 5 7 0
A b bre viati o ns: A D T: a n dr o ge n de pri vati o n t hera p y; A R PI: a n dr o ge n rece pt or pat h wa y i n hi bit or ; C T P: C urre nt Pr oce d ural Ter mi n ol o g y ; G PI: Ge neric Pr o d uct 
I de ntifier; H C P C S: Healt hcare C o m m o n Pr oce d ure C o di n g S yste m; I C D: I nter nati o nal Classificati o n of Diseases; I C D-1 0 -C M : I nter nati o nal Classificati o n of 
Diseases, 1 0 t h Re visi o n, Cli nical M o dificati o n ; I C D-1 0 -P C S: I nter nati o nal Classificati o n of Diseases, 1 0t h Re visi o n, Pr oce d ures ; L H R H: l utei nizi n g h or m o ne–
releasi n g h or m o ne; N S A A: n o n -ster oi dal a nti-a n dr o ge n
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 3 7 of 4 1
A p pe n di x T a ble 2 . Di a g n osis c o des f or c o m or bi dities
C o n diti o ns a n d c o m or bi dities
I C D-1 0 -C M  
N CI c o m or bi dit y i n de x 1
Cere br o v asc ul ar dise ase
G 4 5, G 4 6, 
H 3 4. 0, I 6 0 – I 6 9
C hr o nic p ul m o n ar y dise ase
I 2 7. 8, I 2 7. 9, 
J 4 0– J 4 7, J 6 0–
J 6 7, J 6 8. 4, 
J 7 0. 1, J 7 0. 3
C o n gesti ve he art f ail ure
I 0 9. 9, I 1 1. 0, 
I 1 3. 0, I 1 3. 2, 
I 2 5. 5, I 4 2. 0, 
I 4 2. 5– I 4 2. 9, 
I 4 3, I 5 0, P 2 9. 0
De me nti a
F 0 0 – F 0 3, 
F 0 5. 1, G 3 0, 
G 3 1. 1
Di a betes wit h c hr o nic c o m plic ati o n
E 1 0. 2 – E 1 0. 5, 
E 1 0. 7, E 1 1. 2 –
E 1 1. 5, E 1 1. 7, 
E 1 2. 2 – E 1 2. 5, 
E 1 2. 7, E 1 3. 2 –
E 1 3. 5, E 1 3. 7, 
E 1 4. 2 – E 1 4. 5, 
E 1 4. 7
Di a betes wit h o ut c hr o nic c o m plic ati o n
E 1 0. 0, E 1 0. 1, 
E 1 0. 6, E 1 0. 8, 
E 1 0. 9, E 1 1. 0, 
E 1 1. 1, E 1 1. 6, 
E 1 1. 8, E 1 1. 9, 
E 1 2. 0, E 1 2. 1, 
E 1 2. 6, E 1 2. 8, 
E 1 2. 9, E 1 3. 0, 
E 1 3. 1, E 1 3. 6, 
E 1 3. 8, E 1 3. 9, 
E 1 4. 0, E 1 4. 1, 
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 3 8 of 4 1
E 1 4. 6, E 1 4. 8, 
E 1 4. 9
H e m i ple gi a or p ar a ple gi a
G 0 4. 1, G 1 1. 4, 
G 8 0. 1, G 8 0. 2, 
G 8 1, G 8 2, 
G 8 3. 0 – G 8 3. 4, 
G 8 3. 9
Mil d li ver dise ase
B 1 8, K 7 0. 0 –
K 7 0. 3, K 7 0. 9, 
K 7 1. 3 – K 7 1. 5, 
K 7 1. 7, K 7 3, 
K 7 4, K 7 6. 0, 
K 7 6. 2 – K 7 6. 4, 
K 7 6. 8, K 7 6. 9, 
Z 9 4. 4
M o der ate or se vere li ver dise ase
I 8 5. 0, I 8 5. 9, 
I 8 6. 4, I 9 8. 2, 
K 7 0. 4, K 7 1. 1, 
K 7 2. 1, K 7 2. 9, 
K 7 6. 5, K 7 6. 6, 
K 7 6. 7
Peri p her al v asc ul ar dise ase
I 7 0, I 7 1, I 7 3. 1, 
I 7 3. 8, I 7 3. 9, 
I 7 7. 1, I 7 9. 0, 
I 7 9. 2, K 5 5. 1, 
K 5 5. 8, K 5 5. 9, 
Z 9 5. 8, Z 9 5. 9
Re n al dise ase
I 1 2. 0, I 1 3. 1, 
N 0 3. 2 – N 0 3. 7, 
N 0 5. 2 – N 0 5. 7, 
N 1 8, N 1 9, 
N 2 5. 0, Z 4 9. 0 –
Z 4 9. 2, Z 9 4. 0, 
Z 9 9. 2
I n di vi d u al c o n diti o ns
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 3 9 of 4 1
H y perte nsi o n
H 3 5. 0 3 9, I 1 0 –
I 1 3, I 1 5– I 1 6, 
I 6 7. 4
H y perli pi de mi a
E 7 8. 0 0, 
E 7 8. 0 1, E 7 8. 1, 
E 7 8. 2, E 7 8. 3, 
E 7 8. 4 1, 
E 7 8. 4 9, E 7 8. 5
T y pe II di a betes
E 1 0. 0, E 1 0. 1, 
E 1 0. 6, E 1 0. 8, 
E 1 0. 9, E 1 1. 0, 
E 1 1. 1, E 1 1. 6, 
E 1 1. 8, E 1 1. 9, 
E 1 2. 0, E 1 2. 1, 
E 1 2. 6, E 1 2. 8, 
E 1 2. 9, E 1 3. 0, 
E 1 3. 1, E 1 3. 6, 
E 1 3. 8, E 1 3. 9, 
E 1 4. 0, E 1 4. 1, 
E 1 4. 6, E 1 4. 8, 
E 1 4. 9
Uri n ar y tr act i nfecti o n
C hr o nic o bstr ucti ve p ul m o n ar y dise ase
J 4 0, J 4 1, J 4 2, 
J 4 3, J 4 7, J 4 4. 9
Arr h yt h mi a
I 4 7. 0, I 4 7. 2, 
I 4 9. 0, I 4 6, 
I 4 9. 3, I 4 9. 4 9, 
I 4 7. 9, I 4 9. 4 0, 
I 4 9. 5, I 4 9. 8, 
I 4 9. 9
C o n gesti ve he art f ail ure
I 0 9. 9, I 1 1. 0, 
I 1 3. 0, I 1 3. 2, 
I 2 5. 5, I 4 2. 0, 
I 4 2. 5-I 4 2. 9, 
I 4 3, I 5 0, P 2 9. 0
M y oc ar di al i nf arcti o n
I 2 1, I 2 2, I 2 5. 2
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 0 6 Ma y
2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 0 1-A u g -2 0 2 3  
Pa ge 4 0 of 4 1
Str o ke
I 6 0, I 6 1, I 6 2, 
I 6 4, I 6 5, I 6 7, 
H 3 4. 1, H 3 4. 2 3, 
H 3 4. 2 1, H 3 4. 0
A n gi n a p ect oris
I 2 0
I nfl a m m at or y b o wel dise ase
K 5 0, K 5 1
Ac ute cor o n ar y sy n dr o m e
I 2 4, I 2 1
Se x u al d ysf u ncti o n
F 5 2. 2 1, N 5 2
De pressi o n
F 2 0. 4, F 3 1. 3 -
F 3 1. 5, F 3 2, 
F 3 3, F 3 4. 1, 
F 4 1. 2, F 4 3. 2
A n xiet y
F 0 6. 4, F 4 1, 
F 4 3. 2 2, 
F 4 3. 2 3, F 9 3. 0
C o g niti ve i m p air me nt
G 3 0, G 3 1. 0, 
F 0 1, F 0 5, 
R 4 1. 0, R 4 1. 8 2, 
F 1 0. 1, F 1 0. 2, 
G 3 1. 2, G 3 1. 8 3, 
F 0 2, F 0 3, 
G 3 1. 1, G 3 1. 8 4, 
F 0 6. 7, R 4 1. 3, 
R 4 1. 8 1, 
R 4 1. 8 4 0
H ot fl as hes 
R 2 3. 2
Pri m ar y c a ncers
C 0 0 -C 2 1, 
C 2 2. 1 -C 2 2. 7, 
C 2 3 -C 7 6, 
C 8 0. 1, C 8 0. 2, 
C 8 1 -C 9 6 , C 7 A
A b bre viati o ns: I C D- 9-C M: I nter nati o nal Classificati o n of Diseases, 9 t h Re visi o n, Cli nical M o dificati o n ; I C D-1 0 -C M: I nter nati o nal Classificati o n of  Diseases, 
1 0 t h Re visi o n, Cli nical M o dificati o n; N CI: Nati o nal Ca ncer I nstit ute
[ 1] S o urce: Q ua n, H u de, et al. C o di n g al g orit h ms f or defi ni n g c o m or bi dities i n I C D- 9-C M a n d I C D -1 0 a d m i nistrati ve data. Me dical care ( 2 0 0 5): 1 1 3 0-1 1 3 9. 
A da pte d usi n g c o des f o u n d i n N CI C o m or bi dit y I n de x O ver vie w: htt ps:// healt hcare deli ver y.ca ncer. g o v/seer me dicare/c o nsi derati o n s/c o m or bi dit y. ht ml
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)

Rel u g oli x
C 4 7 5 1 0 0 9 N O N -I N T E R V E N TI O N A L S T U D Y P R O T O C O L
Versi o n 1, 3 1 Ma y 2 0 2 4
P FI Z E R C O N FI D E N TI A L
C T 2 4- WI -G L 0 2 -R F 0 2 5. 0 N o n -I nterve nti o n al St u dy Pr ot oc ol Te m pl ate F or Sec o n d ary D at a C ollecti o n St u dy 
0 1 -A u g -2 0 2 3  
Pa ge 4 1 of 4 1
A p pe n di x T a ble 3 . C o des f or c ortic oster oi ds a n d p ai n me dic ati o ns
Tre at m e nt
G PI
H C P C S
C ortic oster oi ds
2 2, 8 9 1 0, 8 9 1 5 
C 9 2 5 6, J 0 7 0 2, J 0 7 0 4, J 1 0 2 0, J 1 0 3 0, J 1 0 4 0, 
J 1 0 9 4, J 1 1 0 0, J 1 7 0 0, J 1 7 1 0, J 1 7 2 0, J 2 6 5 0, 
J 2 9 2 0, J 2 9 3 0, J 3 3 0 0, J 3 3 0 1, J 3 3 0 2, J 3 3 0 3, 
J 7 3 1 2, J 7 5 0 6, J 7 5 0 9, J 7 5 1 0, J 7 5 1 2, J 7 6 2 4, 
J 7 6 2 6, J 7 6 2 7, J 7 6 3 3, J 7 6 3 4, J 7 6 3 7, J 7 6 3 8, 
J 7 6 8 3, J 7 6 8 4, J 8 5 4 0
P ai n m e dic ati o ns ( a nal gesics)
O pi oi ds
6 5
A b bre viati o ns: G PI: Ge neric Pr o d uct I de ntifier; H C P C S: Healt hcare C o m m o n Pr oce d ure C o di n g S yste m
0 9 0 1 7 7 e 1 a 0 b 0 6 4 d 5\ Fi n al\ Fi n al O n: 1 5- M a y- 2 0 2 4 2 0: 3 7 ( G M T)