A Phase III, 6-Month Self-selection and Actual Use Study for Rx-to-OTC Switch of Rosuvastatin 5 mg Once-daily in Combination With a Web App
Phase: PHASE3
Conditions: High Cholesterol
Sponsor: AstraZeneca

Cli nical St u d y Pr ot oc ol  – v 8. 0
Astra Ze neca
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5
C O N FI D E N TI A L A N D P R O P RI E T A R Y  1
 of 1 5 5
Cli nic al St u d y Pr ot oc ol
St u d y I nter ve nti o n
5 m g R os u vastati n  wit h  a We b 
A p p ( C o m bi nati o n Pr o d uct)
St u d y C o de
D 3 5 6 P L 0 0 0 1 5
Versi o n
8. 0
Date
1 4 Se p 2 0 2 2
T A C Ti C  - Tec h n ol o g y -Assiste d C h olester ol Tri al i n C o ns u mers
A P h ase III, 6 -M o nt h, Self -selecti o n a n d Act u al Use f or R x -t o- 
O T C S witc h of r os u v ast ati n  5 m g o nce -d ail y i n c o m bi n ati o n wit h a 
We b A p p
S p o ns or N a me: Astra Ze neca P har mace uticals L P
Le g al Re gistere d  A d dress: 1 8 0 0 C o nc or d Pi ke, Wil mi n gt o n,
D E 1 9 8 0 5
We b
A p p M a n uf act urer:
I dea E v ol ver
Le g al Re gistere d  A d dress: 5 3 Bri d ge Street, S uite  3 0 2, Br o o kl y n, N Y 1 1 2 0 1
Re g ul at or y A ge nc y I de ntifier  N u m ber(s) : I N D 1 2 4 2 1 0
T his Cli nical St u d y Pr ot oc ol has bee n s u bject t o a peer re vie w acc or di n g t o  Astra Ze neca 
Sta n dar d pr oce d ures. T he Cli nical  St u d y Pr ot oc ol is p u blicl y re gistere d,  a n d t he res ults are 
discl ose d  a n d/ or p u blis he d acc or di n g t o t he Astra Ze neca Gl o bal P olic y o n Bi oet hics  a n d i n 
c o m plia nce wit h pre vaili n g la ws a n d re g ulati o ns.
R e d a ct e d f or P u bli c Di s cl o s ur e
R e d a ct e d f or P u bli c Di s cl o s ur e
Tec h n ol o g y
R e d a ct e d f or P u bli c Di s cl o s ur e
Tec h n ol o g y -
R e d a ct e d f or P u bli c Di s cl o s ur e
-Assiste d
R e d a ct e d f or P u bli c Di s cl o s ur e
Assiste d
M o nt h, Self
R e d a ct e d f or P u bli c Di s cl o s ur e
M o nt h, Self -
R e d a ct e d f or P u bli c Di s cl o s ur e
-
M o nt h, Self -
M o nt h, Self
R e d a ct e d f or P u bli c Di s cl o s ur e
M o nt h, Self -
M o nt h, Self
selecti o n a n d
R e d a ct e d f or P u bli c Di s cl o s ur e
selecti o n a n d
r os u v ast ati n
R e d a ct e d f or P u bli c Di s cl o s ur e
r os u v ast ati n  5 
R e d a ct e d f or P u bli c Di s cl o s ur e
 5 m g
R e d a ct e d f or P u bli c Di s cl o s ur e
m g
R e d a ct e d f or P u bli c Di s cl o s ur e
P har mace uticals
R e d a ct e d f or P u bli c Di s cl o s ur e
P har mace uticals L P
R e d a ct e d f or P u bli c Di s cl o s ur e
L P
Pi ke,
R e d a ct e d f or P u bli c Di s cl o s ur e
Pi ke, Wil mi n gt o n,
R e d a ct e d f or P u bli c Di s cl o s ur e
Wil mi n gt o n,
R e d a ct e d f or P u bli c Di s cl o s ur e
D E
R e d a ct e d f or P u bli c Di s cl o s ur e
D E
 3 0 2, Br o o kl y n, N Y 
R e d a ct e d f or P u bli c Di s cl o s ur e
 3 0 2, Br o o kl y n, N Y 1 1 2 0 1
R e d a ct e d f or P u bli c Di s cl o s ur e
1 1 2 0 1
R e d a ct e d f or P u bli c Di s cl o s ur e
peer re vie w acc or di n g t o
R e d a ct e d f or P u bli c Di s cl o s ur e
peer re vie w acc or di n g t o Astra Ze neca 
R e d a ct e d f or P u bli c Di s cl o s ur e
Astra Ze neca 
 a n d t he 
R e d a ct e d f or P u bli c Di s cl o s ur e
 a n d t he res ults
R e d a ct e d f or P u bli c Di s cl o s ur e
res ults are 
R e d a ct e d f or P u bli c Di s cl o s ur e
are 
Bi oet hics
R e d a ct e d f or P u bli c Di s cl o s ur e
Bi oet hics  a n d i n 
R e d a ct e d f or P u bli c Di s cl o s ur e
 a n d i n 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y   
5 of 1 5 5  
 
T A B L E O F C O N T E N T S  
TI T L E P A G E  ............................................................................................................................. 1 
T A B L E O F C O N T E N T S  .......................................................................................................... 5 
1  
P R O T O C O L S U M M A R Y  ..................................................................................... 9 
1. 1  
S y n o psis .................................................................................................................. 9  
1. 2  
Sc he ma  .................................................................................................................. 1 9 
1. 3  
Sc he d ule of Acti vities  ........................................................................................... 2 0 
2  
I N T R O D U C TI O N ................................................................................................ 2 3 
2. 1  
St u d y Rati o nale  ..................................................................................................... 2 3 
2. 2  
Bac k gr o u n d ........................................................................................................... 2 3  
2. 3  
Be nefit/ Ris k  Assess me nt  ...................................................................................... 2 4 
2. 3. 1  
Ris k  Assess me nt  ................................................................................................... 2 4 
2. 3. 2  
Be nefit  Assess me nt  ............................................................................................... 2 5 
2. 3. 3  
O verall  Be nefit: Ris k  C o ncl usi o n  .......................................................................... 2 6 
3  
O BJ E C TI V E S  A N D  E N D P OI N T S  ...................................................................... 2 7 
3. 1  
E n d p oi nt Rati o nale  ................................................................................................ 3 1 
4  
S T U D Y  D E SI G N  .................................................................................................. 3 5 
4. 1  
O verall  Desi g n  ...................................................................................................... 3 5 
4. 2  
Scie ntific  Rati o nale  f or St u d y Desi g n  ................................................................... 3 6 
4. 3  
J ustificati o n f or D ose  ............................................................................................ 3 8 
4. 4  
E n d  of St u d y Defi niti o n  ........................................................................................ 3 8 
5  
S T U D Y  P O P U L A TI O N  ....................................................................................... 3 9 
5. 1  
Recr uit me nt  Strate g y  ............................................................................................. 3 9 
5. 2  
I ncl usi o n Criteria  ................................................................................................... 4 0 
5. 3  
E xcl usi o n Criteria  ................................................................................................. 4 1 
5. 4  
Lifest yle  C o nsi derati o ns ....................................................................................... 4 2 
5. 5  
Pre -Scree n  Fail ures  ............................................................................................... 4 2 
6  
S T U D Y  I N T E R V E N TI O N................................................................................... 4 3 
6. 1  
St u d y I nter ve nti o n A d mi nistere d  .......................................................................... 4 3 
6. 1. 1  
I n vesti gati o nal Pr o d ucts ....................................................................................... 4 3 
6. 1. 2  
S oft ware  as a C o nstit ue nt Part  ............................................................................... 4 4 
6. 2  
Pre parati o n/ Ha n dli n g/ St ora ge/ Acc o u nta bilit y  of  I nter ve nti o ns .......................... 4 4 
6. 3  
Meas ures  t o Mi ni mize  Bias:  Ra n d o mizati o n a n d Bli n di n g  ................................... 4 5 
6. 4  
St u d y I nter ve nti o n C o m plia nce  ............................................................................. 4 5 
6. 5  
C o nc o mita nt T hera p y  ............................................................................................ 4 5 
6. 5. 1  
Resc ue  Me dici ne  ................................................................................................... 4 6 
6. 6  
D ose M o dificati o n  ................................................................................................ 4 6 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y   
6 of 1 5 5  
 
6. 7  
I nter ve nti o n after t he E n d  of t he St u d y  ................................................................. 4 6 
7  
DI S C O N TI N U A TI O N  O F  S T U D Y  I N T E R V E N TI O N A N D P A R TI CI P A N T 
DI S C O N TI N U A TI O N/ WI T H D R A W A L  ............................................................ 4 6 
7. 1  
Disc o nti n uati o n of St u d y I nter ve nti o n .................................................................. 4 6 
7. 2  
Partici pa nt  Wit h dra wal  fr o m t he St u d y  ................................................................. 4 7 
7. 3  
L ost  t o F oll o w -u p  .................................................................................................. 4 7 
8  
S T U D Y  A S S E S S M E N T S  A N D  P R O C E D U R E S  ................................................ 4 8 
8. 1  
e Diar y ................................................................................................................... 5 6 
8. 2  
Efficac y  Assess me nts  ........................................................................................... 5 7 
8. 3  
Safet y  Assess me nts  ............................................................................................... 5 7 
8. 3. 1  
P h ysical  E xa mi nati o ns  .......................................................................................... 5 7 
8. 3. 2  
Vital  Si g ns  ............................................................................................................. 5 8 
8. 3. 3  
Electr ocar di o gra ms  ............................................................................................... 5 8 
8. 3. 4  
Cli nical  Safet y  La b orat or y Assess me nts  ............................................................... 5 8 
8. 3. 5  
Ot her  Safet y  Assess me nts  ..................................................................................... 5 8 
8. 4  
A d verse E ve nts a n d Seri o us A d verse E ve nts  ........................................................ 5 8 
8. 4. 1  
Ti me  Peri o d  a n d Fre q ue nc y f or C ollecti n g  A E  a n d S A E  I nf or mati o n .................. 5 9 
8. 4. 2  
F oll o w- u p of  A Es  a n d S A Es  ................................................................................. 5 9 
8. 4. 3  
Ca usalit y  C ollecti o n  ............................................................................................. 6 0 
8. 4. 4  
A d verse E ve nts Base d  o n Si g ns a n d S y m pt o ms  ................................................... 6 0 
8. 4. 5  
A d verse E ve nts Base d  o n E xa mi nati o ns a n d Tests  ............................................... 6 1 
8. 4. 6  
Re p orti n g of Seri o us A d verse E ve nts  ................................................................... 6 1 
8. 4. 6. 1  
Re p orti n g of A Es/ S A Es  i n Relati o n  t o C O VI D -1 9  .............................................. 6 2 
8. 4. 7  
Pre g na nc y ............................................................................................................. 6 2  
8. 4. 7. 1  
Mater nal  E x p os ure  ................................................................................................ 6 2 
8. 4. 8  
Me dicati o n  Err or  ................................................................................................... 6 3 
8. 4. 9  
S oft ware  as a C o nstit ue nt Part  ............................................................................... 6 3 
8. 5  
O ver d ose ............................................................................................................... 6 4  
8. 6  
H u ma n  Bi ol o gical Sa m ples  ................................................................................... 6 4 
8. 6. 1  
P har mac o ki netics  .................................................................................................. 6 4 
8. 6. 2  
P har mac o d y na mics ............................................................................................... 6 4  
8. 7  
H u ma n  Bi ol o gical Sa m ple  Bi o mar kers  ................................................................. 6 4 
8. 7. 1  
C ollecti o n  of  Ma n dat or y Sa m ples f or Bi o mar ker Anal ysis  ................................... 6 4 
8. 7. 2  
C ollecti o n  of  Opti o nal Bi o mar ker Sa m ples ........................................................... 6 4 
8. 7. 3  
Ot her  St u d y-Relate d  Bi o mar ker  Researc h ............................................................ 6 5 
8. 8  
O pti o nal Ge n o mics I nitiati ve Sa m ple  ................................................................... 6 5 
8. 9  
Healt h  Ec o n o mics O R  Me dical  Res o urce Utilizati o n  a n d Healt h Ec o n o mics  ...... 6 5 
9  
S T A TI S TI C A L  C O N SI D E R A TI O N S  ................................................................. 6 5 
9. 1  
Statistical  H y p ot heses  ........................................................................................... 6 5 
9. 2  
Sa m ple  Size  Deter mi nati o n  .................................................................................. 6 5 
9. 3  
P o p ulati o ns f or A nal yses  ....................................................................................... 6 8 
9. 4  
Statistical  A nal yses  ............................................................................................... 6 9 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y   
7 of 1 5 5  
 
9. 4. 1  
Ge neral  C o nsi derati o ns ......................................................................................... 6 9 
9. 4. 1. 1  
S u b gr o u p A nal yses  ............................................................................................... 6 9 
9. 4. 1. 2  
We b  A p p  Rec or ds  ................................................................................................. 6 9 
9. 4. 1. 3  
Miti gati o n  Pla n  ...................................................................................................... 7 0 
9. 4. 1. 4  
Ma na gi n g Varia bilit y  of  La b orat or y, Bl o o d Press ure a n d Waist Circ u mfere nce 
Data  fr o m Differe nt  S o urces  ................................................................................. 7 6 
9. 4. 2  
St u d y E n d p oi nts .................................................................................................... 7 9  
9. 4. 2. 1  
Pri mar y  E n d p oi nt(s) ............................................................................................. 7 9 
9. 4. 2. 2  
Sec o n dar y E n d p oi nt(s) ......................................................................................... 8 6  
 
 
9. 4. 3  
Safet y  .................................................................................................................... 9 1 
9. 4. 4  
E val uati o n of SI L S 2  Literac y  T hres h ol d  ............................................................... 9 2 
9. 5  
I nteri m A nal yses  ................................................................................................... 9 2 
9. 6  
Data  M o nit ori n g  C o m mittee  ................................................................................. 9 2 
1 0  
S U P P O R TI N G  D O C U M E N T A TI O N  A N D  O P E R A TI O N A L 
C O N SI D E R A TI O N S  ............................................................................................ 9 3 
1 1  
A P P E N DI C E S  ...................................................................................................... 9 3 
 
LI S T O F FI G U R E S  
Fi g ure 1  
St u d y Desi g n ............................................................................................... 1 9  
Fi g ure 2 
T w o - b y- F o ur Ta ble  Ill ustrati n g P ossi ble Self -Selecti o n  O utc o mes  f or 
I nitial T A S S Assess me nt ............................................................................. 8 0 
Fi g ure 3 
T hree - b y-T hree  Ta ble  Ill ustrati n g P ossi ble Self -Selecti o n  O utc o mes f or 
Fi nal Use Assess me nt  ................................................................................. 8 2 
 
LI S T O F T A B L E S  
Ta ble  1  
Sc he d ule of Acti vities  .................................................................................. 2 0 
Ta ble  2  
I n vesti gati o nal Pr o d ucts  .............................................................................. 4 3 
Ta ble  3 
Esti mate d N u m ber  of S u bjects/ Partici pa nts  b y St u d y Sta ge  ....................... 6 6 
Ta ble  4  
P o p ulati o ns f or A nal ysis  .............................................................................. 6 8 
Ta ble  5 
I nitial Self -Selecti o n  Miti gati o ns  ................................................................. 7 1 
Ta ble  6 
Use Peri o d  Miti gati o ns  ................................................................................ 7 3 
 
 
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Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y   
9 of 1 5 5  
 
1  
P R O T O C O L S U M M A R Y  
1. 1  
S y n o psis  
Pr ot oc ol Title:  A P hase III, 6 - M o nt h Self- Selecti o n a n d Act ual Use St u d y f or R x-t o-O T C 
S witc h of r os u vastati n 5 m g O nce- dail y  
S h ort Title:  Tec h n ol o g y-Assiste d C h olester ol Trial i n C o ns u mers ( T A C Ti C)  
R ati o n ale:   F or o ver a ce nt ur y, heart disease has re mai ne d t he lea di n g ca use of deat h f or b ot h 
me n a n d w o me n i n t he U nite d  States  a n d w orl d wi de (Merca d o et al 2 0 1 5 ). Ele vate d 
c h olester ol  is a ke y ris k fact or f or heart disease, a n d w hile l o weri n g c h olester ol wit h stati n 
dr u gs re d uces car di o vasc ular m or bi dit y a n d m ortalit y, o nl y a b o ut half of t he pe o ple i n t he 
U nite d States w h o re q uire t hera p y are c urre ntl y treate d (Merca d o et al 2 0 1 5 ). T his re prese nts 
a s u bsta ntial p u blic healt h iss ue f or t he U nite d States.  W hile t here are n u mer o us reas o ns w h y 
pe o ple are n ot treate d, w hat is clear is t hat easier access t o safe, effecti ve, a n d aff or da ble 
t hera p y w o ul d ha ve a si g nifica nt p ositi ve  i m pact o n p u blic healt h.  O ne wa y t o si m plif y 
access t o stati n t hera p y w o ul d be t o ma ke it a vaila ble t o c o ns u mers wit h o ut a prescri pti o n 
(e. g., O ver-t he-C o u nter [ O T C]).  Past atte m pts t o  ac hie ve a n O T C  s witc h f or stati n treat me nt 
ha ve faile d d ue t o c o ncer ns a b o ut t he efficac y of t he stati ns teste d, a n d beca use c o ns u mers 
were u na ble t o pr o perl y self- select. T he Crest or O T C pr o gra m a d dresses t hese c o ncer ns b y 
usi n g Crest or 5 m g (a safe a n d hi g hl y effecti ve d ose of r os u vasta ti n wit h mi ni mal i nteracti o ns 
[Astra Ze neca P har mace uticals L P 2 0 2 1 ]) wit h a We b A p p t hat feat ures a Tec h n ol o g y- 
Assiste d Self -Selecti o n ( T A S S) t o ol.  T he  T A S S t o ol e ns ures t he me dici ne is o nl y ma de 
a vaila ble t o c o ns u mers f or w h o m it is safe a n d a p pr o priate. C o m plete d st u dies testi n g Dr u g 
Facts  La bel  ( D F L) c o m pre he nsi o n, C o ns u mer I nf or mati o n Leaflet  ( CI L) c o m pre he nsi o n, We b 
A p p c o m pre he nsi o n, H u ma n Fact ors, Tar gete d Self - Selecti o n, a n d All-c o mers Self -Selecti o n 
ha ve s h o w n t hat t his a p pr oac h is via ble.   Base d o n t he p ositi ve res ults fr o m t hese pi v otal 
st u dies, Astra Ze neca is rea d y t o pr ocee d wit h t he  Act ual Use St u d y ( A U S).  
P ur p ose:  T he  p ur p ose of t his  A U S  is t o e val uate t he e xte nt t o w hic h  partici pa nts  ca n safel y 
a n d effecti vel y self -select, p urc hase, a n d use Crest or O T C 5 m g f or a 6- m o nt h peri o d 
acc or di n g t o t he la bel. I nte gral t o t hese e val uati o ns will be t he a bilit y of partici pa nts t o 
c orrectl y e nter t heir healt h i nf or mati o n i nt o t he We b A p p. 

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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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O bjecti ves  
E n d p oi nts  
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 3  of 1 5 5  
 
O bjecti ves  
E n d p oi nts  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
O ver all Desi g n  
T his is a 6 - m o nt h, si n gle-ar m, tec h n ol o g y-assiste d Self - Selecti o n a n d Act ual Use St u d y t o 
e val uate t he use of r os u vastati n 5  m g i n  c o m bi nati o n wit h a We b  A p p; t here is n o c o m parat or 
or c o ntr ol dr u g.  T he st u d y will be c o n d ucte d i n a p o p ulati o n of all- c o mers c o m prise d of 
i ntereste d s u bjects w h o  res p o n d t o a n a d f or a st u d y a b o ut l o weri n g c h olester ol, c o m plete  pre - 
scree ni n g pr oce d ures, a n d c o m plete a We b A p p t hat feat ures a T A S S t o ol. T he T A S S t o ol is 
me dical de vice s oft ware t hat i nc or p orates a n al g orit h m  base d  o n t he A merica n  Heart  
Ass ociati o n  ( A H A)/ A merica n C olle ge  of Car di ol o g y ( A C C) car di o vasc ular ris k calc ulat or, t he 
2 0 1 8 G ui deli ne o n t he Ma na ge me nt of Bl o o d C h olester ol (Gr u n d y et al 2 0 1 8 ) an d t he Crest or 
O T C  D F L  i n or der t o deter mi ne  if a c o ns u mer w o ul d q ualif y f or treat me nt wit h 
n o n prescri pti o n r os u vastati n calci u m, a m o derate- i nte nsit y stati n t hera p y. 
S u bjects are eli gi ble t o p urc hase n o n prescri pti o n r os u vastati n calci u m if t he y meet t he 
re q uire me nts f or safe use acc or di n g t o t he D F L, 2 0 1 8 C h olester ol Treat me nt G ui deli nes 
(Gr u n d y et al 2 0 1 8 ) a n d ha ve a n a p pr o priate at her oscler otic car di o vasc ular disease ( A S C V D) 
ris k sc ore. 
S u bjects w h o  ha ve a “ D o N ot  Use”  o utc o me or a n  “ As k a D oct or” o utc o me a n d d o n ot c o nfir m 
wit hi n t he  We b  A p p t hat t he y s p o ke t o a d oct or will n ot be  per mitte d  i nt o t he h o me use p hase 
of t he st u d y. 
 
 
 
 
 
 
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Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 4  of 1 5 5  
 
T he T A C Ti C st u d y will be c o n d ucte d i n 3 0- 5 0 mar kets t hr o u g h o ut t he U nite d States. All 
visits will be c o m plete d utilizi n g virt ual met h o ds s uc h as virt ual visits c o n d ucte d b y t he 
Ce n tral Me dical O perati o ns Gr o u p ( C M O G) st u d y staff. T he C M O G is c o m prise d of 
cli nicia ns  t hat i ncl u de re gistere d n urses, n urse practiti o ners, p h ysicia n assista nts a n d me dical 
d oct ors. T here  will  be a Virt ual  Visit  1, 6 0- da y a n d 1 2 0- da y p h o ne calls, a Virt ual  Visit  2 a n d a 
3 0- da y f oll o w- u p p h o ne call p ost-st u d y dr u g disc o nti n uati o n t o assess partici pa nts stat us wit h 
re gar d t o a d verse e ve nts ( A Es). 
I ncl usi o n Criteri a  
1  
Males, 2 0 -7 5  years  of a ge 
2  
Fe males, 2 0 - 7 5 years of a ge ( T his i ncl usi o n criteri o n will be a p plie d u ntil 5 0 fe males 
u n der t he a ge of 5 0 years c o m plete t he i nitial T A S S assess me nt i n t he We b A p p.  After 
t his q u ota of 5 0 fe males u n der t he a ge of 5 0 years  ol d is met, t he i ncl usi o n criteri o n will  
be re vise d t o fe males 5 0- 7 5 years ol d). 
3  
Res p o n d t o a d vertisi n g re gar di n g a  c o ncer n a b o ut hi g h c h olester ol or heart  healt h  
4  
A ble  t o rea d s pea k a n d u n dersta n d E n glis h  
 
A d diti o nal Criteria  f or I ncl usi o n f or Act ual  Use  (at Virt ual  Visit  1)  
1  
Partici pa nt  rea ds a n d si g ns t he I nf or me d C o nse nt f or m. 
 
E xcl usi o n Criteri a  
1  
T he  partici pa nt  or a n y o ne i n t heir h o use h ol d is c urre ntl y e m pl o ye d b y a n y of t he 
f oll o wi n g: 
− 
A p har mac y  or p har mace utical c o m pa n y 
− 
A c o ns u mer healt hcare  c o m pa n y 
− 
A ma n ufact urer  of  me dici nes  
− 
A ma na ge d care  or healt h i ns ura nce c o m pa n y 
− 
A healt hcare practice  
− 
A n  e m pl o yee of Astra Ze neca  or C o nce ntrics Researc h  
2  
T he  partici pa nt  has e ver bee n  trai ne d or e m pl o ye d as a healt hcare  pr ofessi o nal ( p h ysicia n, 
n urse, n urse practiti o ner, p h ysicia n assista nt, p har macist).  
3  
T he  partici pa nt  has,  or ca n n ot recall w het her he/s he  has,  recei ve d a n i n vesti gati o nal 
t hera p y as part of a cli nical trial i n t he pre vi o us t wel ve ( 1 2) m o nt hs. 
4  
T he  partici pa nt  is n ot willi n g  t o pr o vi de  c o ntact i nf or mati o n. 
5  
Pre vi o us e nr oll me nt i n t he prese nt st u d y. 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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6  
T he  partici pa nt  has a maili n g  a d dress i n Alas ka, or t heir maili n g  a d dress  is a P ost Office 
( P O) B o x. 
7  
T he  partici pa nt  is n ot willi n g  t o c o m plete a n  e Diar y. 
8  
T he partici pa nt is a w o ma n of c hil d beari n g p ote ntial a n d is n ot f oll o wi n g c o ntrace pti o n 
g ui deli nes or is  n ot  willi n g  t o f oll o w c o ntrace pti o n g ui deli nes i ncl u di n g practici n g 
a bsti ne nce or usi n g at least 1 of t he f oll o wi n g acce pta ble met h o ds of birt h c o ntr ol f or at 
least 1 m o nt h pri or t o e ntr y i nt o t he st u d y a n d f or 1 m o nt h after st u d y c o m pleti o n: 
h or m o nal – oral, i m pla nta ble, i njecta ble, or tra ns der mal; mec ha nical – s per mici de i n 
c o nj u ncti o n wit h  a barrier s uc h as a  c o n d o m or dia p hra g m; i ntra uteri ne de vice; or s ur gical 
sterilizati o n of part ner. 
9  
T he  partici pa nt  d oes n ot ha ve access  t o t he i nter net. 
1 0  T he  partici pa nt  d oes n ot ha ve a n e mail a d dress or t he a bilit y t o recei ve e mails. 
1 1  T he partici pa nt res p o n ds t o t he Si n gle Ite m Literac y Scree ner 2 ( SI L S 2) q uesti o n  (C he w 
et al 2 0 0 8), “H o w c o nfi de nt are y o u filli n g o ut me dical f or ms b y y o urself?” , wit h eit her 
‘e xtre mel y’ or ‘ q uite a bit.’ (If t he q u ota f or n or mal literac y is met, b ut t he li mite d literac y 
tar get is n ot met, t he SI L S 2 e xcl usi o n will be use d t o hel p i ncrease t he perce nta ge of 
li mite d literac y partici pa nts  at Virt ual  Visit  1. Partici pa nts  i de ntifie d as n or mal literac y b y 
Ra pi d Esti mate of A d ult Literac y i n Me dici ne [ R E A L M] testi n g at Virt ual Visit  1 will  n ot 
be e xcl u de d fr o m e ntr y i nt o t he treat me nt p hase of t he st u d y.) 
1 2  I na bilit y t o c o n d uct i nter vie ws i n a pri vate l ocati o n s o t hat se nsiti ve i nf or mati o n a b o ut t he 
partici pa nt  or st u d y w o ul d n ot be o ver hear d b y ot hers  n ot per mitte d  t o hear  s uc h 
i nf or mati o n. 
 
A d diti o nal Criteria  f or E xcl usi o n fr o m Act ual  Use  (at Virt ual  Visit  1)  
C o nfir mati o n  b y C o nce ntrics Ce ntral Me dical  O perati o ns Gr o u p ( C M O G) cli nicia n: 
1  
T hat  t he partici pa nt  is pre g na nt, as deter mi ne d  b y  a n a p pr o ve d self-a d mi nistere d  O T C 
uri ne pre g na nc y test ( U P T) c o n d ucte d f or all fe male partici pa nts of c hil d beari n g p ote ntial 
( Fe male partici pa nts w h o are n ot p ost- me n o pa usal or s ur gicall y sterile). 
2  
T hat  t he partici pa nt  is breast fee di n g. 
3  
T hat t he partici pa nt  has a n aller g y t o r os u vastati n. 
 
Discl os ure  St ate me nt : T his  is a 6- m o nt h, si n gle-ar m, u nc o ntr olle d tec h n ol o g y-assiste d self - 
selecti o n a n d act ual use st u d y  t o e val uate t he use of r os u vastati n  5 m g  i n c o m bi nati o n wit h  a 
We b  A p p. 

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N u m ber of  P artici p a nts:  
T he tar get f or t his st u d y is at least 5 0 0 e val ua ble partici pa nts wit h a g oal t o ha ve 1 0 0 of 
li mite d literac y. It is e x pecte d t hat a p pr o xi matel y 8 0, 0 0 0 c o ns u mers will c o ntact t he Call 
Ce nter f or pre -scree ni n g i n res p o nse t o a d vertisi n g. Tra dit i o nal (i.e., tele visi o n, pri nt) a n d 
di gital a d vertisi n g a p pr oac hes  will  be  utilize d  f or recr uit me nt. T he  ta ble bel o w  s u m marizes t he 
esti mates a n d perce nta ge dr o ps at eac h ste p fr o m t he i nitial call i nt o t he Call Ce nter t hr o u g h 
c o m pleti o n of t he st u d y. 
Calls  i nt o Call Ce nter  
Esti mate d  8 0, 0 0 0 calls 
Se nt  t he We b  Li n k  
  Ass u mes:  
  Pre -scree n Fail rate = 2 4 % Q ualifie d 
    Ref use d  rate = 8 %  
Esti mate d  5 4, 4 0 0 s u bjects 
C o m plete  t he We b  Li n k  ( 6 6 %) 
Esti mate d  3 5, 9 0 0  s u bjects 
Q ualif y  as “ O k t o Use” ( ~  5 %)  
Esti mate d  1, 8 0 0 s u bjects 
Sc he d ule Virt ual  Visit  1 ( 8 5 %) 
Esti mate d  1, 5 2 5 s u bjects 
E nr olle d  –  C o m plete  c o nse nt  at Virt ual  Visit 1 
( 8 0 %) 
Esti mate d  1, 2 2 0  partici pa nts  
E nter  Use P hase of  t he St u d y ( 8 3 %) 
Esti mate d  1, 0 0 0 partici pa nts  
Wit h dra wals/ L ost -t o f oll o w- u p d uri n g use ( ~ 5 0 %) 
Esti mate d 5 0 0  partici pa nts  
E val ua ble  partici pa nts * 
Esti mate d 5 0 0  partici pa nts  
* E val ua ble f or t he sec o n d c o -pri mar y e n d p oi nt, O verall C orrect Fi nal Use O utc o me  
 
N ote : “ E nr olle d” is defi ne d as a partici pa nt’s a gree me nt t o partici pate i n a cli nical st u d y 
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt f or m (I C F) pr ocess. S u bjects w h o are pre- 
scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y b ut d o n ot si g n c o nse nt, are 
defi ne d as “ pre -scree n fail ures.” See Secti o n  9. 3  for f urt her detail o n t he defi niti o n of pre - 
scree n a n d scree n fail ures.  
I nter ve nti o n Gr o u ps a n d D ur ati o n: T his is a si n gle -ar m, u nc o ntr olle d Act ual Use St u d y . 
T he t otal d urati o n of partici pati o n is a p pr o xi matel y 7- 8 m o nt hs w hic h i ncl u des a 4- wee k 
wi n d o w t o use t he We b  A p p  at h o me a n d c o m plete Virt ual  Visit 1, 6  m o nt hs f or t he h o me use 
peri o d, c o m pleti o n  of a Virt ual  Visit  2 after t he use  peri o d, a n d a 3 0- da y f oll o w- u p p h o ne call. 
T he pr ot oc ol d oes n ot call f or d ose a dj ust me nts t o be ma de b y i n vesti gat ors or partici pa nts. 
T his  st u d y will  e val uate self-selecti o n a n d act ual use i ncl u di n g c o m plia nce  wit h  la bel 
war ni n gs a n d directi o ns. T he d ose is a 5 m g ta blet o nce a da y.  

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1 7  of 1 5 5  
 
D at a  M o nit ori n g  C o m mittee:  N o  
St atistic al Met h o ds:  T he first t w o c o -pri mar y a nal yses will e val uate t he perce nta ge of 
partici pa nts w h o ac hie ve d a n O verall C orrect I nitial T A S S O utc o me at i nitial self -selecti o n 
( S S P o p ulati o n) a n d a n O verall C orrect Fi nal Use O utc o me at t he fi nal use assess me nt ( Per 
Pr ot oc ol p o p ulati o n). F or t hese e val uati o ns, t he  o utc o mes o btai ne d b y t he partici pa nt will be 
c o m pare d t o t he o utc o mes o btai ne d b y t he C M O G cli nicia n.  T he S S P o p ulati o n i ncl u des all 
partici pa nts w h o si g n t he I C F. T he Per Pr ot oc ol p o p ulati o n i ncl u des all partici pa nts i n t he 
A U S I T T p o p ulati o n w h o c o m plete a Virt ual Visit 2 a n d partici pa nts w h o ha ve disc o nti n ue d 
b ut ha ve s ufficie nt me dical a n d me dicati o n hist or y i nf or mati o n a n d, w he n necessar y, a 
verifie d l o w - de nsit y li p o pr otei n-c h olester ol ( L D L - C) c ollecte d pri or t o st o p pi n g t he st u d y t o 
deter mi ne a fi nal use o utc o me .  T he t hir d c o-pri mar y  a nal ysis will  e val uate perce nt c ha n ge 
fr o m baseli ne  ( P C F B) i n verifie d  L D L - C val ues t o Visit 2 i n partici pa nts re gar dless of t heir 
fi nal use o utc o me. 
T here  are t hree c o-pri mar y  e n d p oi nts: 
1  
Perce nta ge  of partici pa nts  wit h  a n O verall  C orrect  (c orrect + miti gate d) I nitial T A S S 
O utc o me at t he i nitial self -selecti o n ( T hres h ol d:  8 5 % l o wer b o u n d [ L B]). 
2  
Perce nta ge  of partici pa nts  wit h  a n O verall  C orrect  (c orrect + miti gate d)  Fi nal  Use 
O utc o me at t he fi nal use assess me nt ( T hres h ol d: 8 5 % [ L B]).  
3  
Perce nt  c ha n ge fr o m baseli ne  i n verifie d  L D L - C t o Visit  2 ( T hres h ol d: -1 5 %  u p per b o u n d 
[ U B], -2 0 % p oi nt esti mate).  
 
T he sa m ple size is base d o n p o weri n g t he st u d y f or t he c o - pri mar y e n d p oi nts. T he e val uati o n 
of t he first c o -pri mar y e n d p oi nt o n t he O verall C orrect I nitial T A S S O utc o me will ha ve a 
sa m ple size of a p pr o xi matel y 1, 2 2 0; h o we ver, n ot all of t hese partici pa nts ma y ha ve a n 
O verall C orrect I nitial T A S S O utc o me. As part of t he pri mar y a nal ysis of t his e n d p oi nt, a n y 
partici pa nts  wit h  a missi n g  O verall  C orrect  I nitial T A S S O utc o me  will  be  i m p ute d usi n g w orst 
case i m p utati o n (i.e., as i nc orrect). As s uc h, it is u n k n o w n e xactl y h o w t he tr ue self- selecti o n 
rate will  be affecte d  base d  o n t his i m p utati o n. T heref ore, t he res ulti n g p o wer ass u mi n g vari o us 
tr ue self-selecti o n rates i n or der t o de m o nstrate t hat t he L B of t he 9 5 % e xact bi n o mial 
c o nfi de nce i nter val ( CI) is greater t ha n  8 5 % wit h a  sa m ple of 1, 2 2 0 partici pa nts is prese nte d i n 
t he ta ble bel o w: 

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Tr ue  Self -Selecti o n  
Rate  
 
P o wer  
Tr ue Self -Selecti o n  
Rate  
 
P o wer  
8 8. 2 4 %  
9 0 %  
8 8. 5 7 %  
9 5 %  
8 8. 3 0 %  
9 1 %  
8 8. 6 7 %  
9 6 %  
8 8. 3 5 %  
9 2 %  
8 8. 7 8 %  
9 7 %  
8 8. 4 2 %  
9 3 %  
8 8. 9 3 %  
9 8 %  
8 8. 4 9 %  
9 4 %  
9 0. 0 0 %  
> 9 9 %  
 
E val uati o n of t he sec o n d c o-pri mar y  e n d p oi nt o n t he O verall  C orrect  Fi nal  Use  O utc o me will 
ha ve a sa m ple size of at least 5 0 0 partici pa nts.  A sa m ple of 5 0 0 partici pa nts  w o ul d pr o vi de at 
least 9 0 % p o wer t o de m o nstrate t hat t he l o wer b o u n d of t he 9 5 % e xact bi n o mial CI is greater 
t ha n 8 5 % f or t he fi nal use e n d p oi nt, ass u mi n g t hat t he tr ue c orrect fi nal use o utc o me rate is 
9 0 %.  
F or eac h  of t he t w o c o-pri mar y  e n d p oi nts assessi n g  O verall  C orrect  I nitial T A S S  O utc o me a n d 
O verall C orrect Fi nal Use O utc o m e, t he f oll o wi n g h y p ot hesis will be e val uate d: 
H 0: P ≤ 8 5 %  vs. H1: P > 8 5 %  
T he  a b o ve n ull h y p ot hesis will be  rejecte d i n fa v or of t he alter nati ve  if t he l o wer b o u n d of t he 
t w o-si de d 9 5 % e xact bi n o mial (i.e., Cl o p per-Pears o n) CI is greater t ha n 8 5 %.  
F or t he t hir d c o-pri mar y  e n d p oi nt, t he  P C F B  i n verifie d  L D L - C val ues t o Visit  is c o m p ute d as 
f oll o ws: 
 
P C F B  = 
1 0 0 *( Verifie d  L D L -C  val ue  at Visit 2  –  Verifie d  L D L -C  val ue  at 
Baseli ne)  
Verifie d  L D L -C  val ue  at Baseli ne  
 
w here t he verifie d L D L - C val ue  at i nitial selecti o n will  ser ve as Baseli ne.  Ne gati ve val ues i n 
P C F B  re prese nt a decrease  i n L D L -C.  
It is a ntici pate d t hat at least 4 5 0 partici pa nts will be i ncl u de d i n t he e val uati o n of t his c o- 
pri mar y e n d p oi nt. Ass u mi n g a tr ue mea n P C F B of - 2 5 % wit h a sta n dar d de viati o n of 2 5 %, a 
sa m ple size of 4 5 0 partici pa nts  w o ul d pr o vi de greater t ha n  9 9 % p o wer t o test t he f oll o wi n g set 
of h y p ot heses usi n g a o ne- sa m ple t-test at a n α = 0. 0 2 5 of si g nifica nce: 
H 0: μ ≥ - 1 5 % vs. H1: μ  < -1 5 %  

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w here  µ is  t he mea n  P C F B  i n verifie d  L D L - C t o Visit  2. T he  a b o ve n ull h y p ot hesis will  be 
rejecte d i n fa v or of t he alter nati ve if t he u p per b o u n d of t he t w o-si de d 9 5 % c o nfi de nce 
i nter val o n t he mea n P C F B i n verifie d L D L-C t o  Visit 2 is less t ha n -1 5 %.  
1. 2  
Sc he m a  
Fi g ure  1 
St u d y Desi g n  
Pre -scree n 
P h o ne C all or 
O nli ne Pre -
scree ner 
 
 
 
 
Self -selecti o n 
Virt u al Visit 1  
H o me Use Peri o d  
Virt u al Visit 2  
3 0 -D a y P ost Use  
We b A p p  
( Re m ote 
C o m pleti o n) 
 
 
E nr oll me nt  
 
 
 
 
St u d y Dr u g 
Deli ver y  
 
 
 
P h o ne  
C all  
 
 
 
P h o ne  
C all  
 
 
Fi n al Visit  
 
 
 
P h o ne  
C all  
 
 
D a y - 3 0 
( + 1 4) 
 
 
D a y 0  
 
 
D a y 6 0  
( +/- 7)  
 
 
D a y 1 2 0  
( +/- 7)  
 
 
D a y 1 8 0  
(-7 / + 1 4)  
 
D a y 2 1 0 [ or 3 0 
d a ys after st u d y 
dr u g 
disc o nti n u ati o n] 
( + 1 4 d a ys) 

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1. 3  
Sc he d ule of Acti vities  
T a ble  1 
Sc he d ule  of Acti vities   
 
 
 
Pr oce d ures  
Pre -scree n P h o ne  
C all or  O nli ne  Pre -
scree ner 
Self -selecti o n 
Virt u al  Visit  1 
H o me  Use  Peri o d  
Virt u al  Visit  2 
3 0 -d a y  P ost  Use  
We b A p p  ( Re m ote 
C o m pleti o n)  
E nr oll me nt  
Dr u g Deli ver y  
P h o ne 
C all g  
P h o ne C all g  
Fi n al  Visit  
P h o ne  C all  
 
D a y  -
3 0  
D a y  0 
D a y  6 0  
D a y  1 2 0  
D a y  1 8 0  
D a y  2 1 0  or  3 0 
d a ys after 
st u d y dr u g 
disc o nti n u ati o n  
Visit  Wi n d o w  
+ 1 4 k 
 
±  7 
±  7 
- 7/ + 1 4  
+ 1 4  
A d vertisi n g  ( Tra diti o nal/ Di gital) 
X  
 
 
 
 
 
 
 
S u bject  c o m pletes pre -scree ni n gl 
•  I ncl usi o n/ E xcl usi o n 
•  De m o gra p hics  
•  SI L S 2  
•  Pri vac y Ac k n o wle d g me nt  
•  St u d y O ver vie w  
•  E mail  Li n k t o t h ose w h o 
q ualif y  
 
 
 
 
X 
 
 
 
 
 
 
 
S u bject  c o m pletes We b  A p p:  
•  D N U  = ter mi nate 
•  A A D B U  = if n ot O K  t o 
Use,  ter mi nate 
•  A A D B U  = if O K  t o Use, 
c o nti n ue 
•  O K  t o Use  = c o nti n ue 
 
 
 
 
X 
 
 
 
 
 
 
I nitial p urc hase of dr u g a  
 
X 
 
 
 
 
 
 
S u bject  c o ntacts Call  Ce nter  t o 
sc he d ule Virt ual Visit  1 
 
X 
 
 
 
 
 
 
Partici pa nt  c o m pletes Virt ual Visit  1  
 
X  
 
 
 
 
 
I D c hec k 
 
 
X  
 
 
 
 
 
Ce ntral  Assess or  c o nfir ms verifie d  
dia g n ostic n u m bers  if a vaila ble  ( T C, 
H D L - C, L D L -C, T G, B P, hs -C R P, 
C A C sc ore, a n d waist circ u mfere nce 
as a p plica ble) b 
 
 
X 
 
 
 
X h 
 

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Pr oce d ures  
Pre -scree n P h o ne  
C all or  O nli ne  Pre -
scree ner 
Self -selecti o n 
Virt u al  Visit  1 
H o me  Use  Peri o d  
Virt u al  Visit  2 
3 0 -d a y  P ost  Use  
We b A p p  ( Re m ote 
C o m pleti o n)  
E nr oll me nt  
Dr u g Deli ver y  
P h o ne 
C all g  
P h o ne C all g  
Fi n al  Visit  
P h o ne  C all  
 
D a y  -
3 0  
D a y  0 
D a y  6 0  
D a y  1 2 0  
D a y  1 8 0  
D a y  2 1 0  or  3 0 
d a ys after 
st u d y dr u g 
disc o nti n u ati o n  
Visit  Wi n d o w  
+ 1 4 k 
 
±  7 
±  7 
- 7/ + 1 4  
+ 1 4  
L ocal  testi n g site, h o me  test kit, 
a n d/ or h o me B P m o nit or, if n o 
verifie d n u m bers are a vaila ble ( T C, 
H D L -C, L D L -C, T G, B P, hs- C R P )b  
. Visit  t o be resc he d ule d if verifie d 
n u m bers are n ot pr o vi de d.  
 
 
 
 
 
X 
 
 
 
 
 
 
X
h  
 
Electr o nic  i nf or me d c o nse nt 
 
 
X  
 
 
 
 
 
Uri ne  pre g na nc y  test f or w o me n of  
c hil d beari n g p ote ntial m  
 
 
X 
 
 
 
X 
 
R E A L M  Test  
 
 
X  
 
 
 
 
 
C M O G c o n d ucts tar gete d me dical  
a n d me dicati o n  hist or yc  
 
 
X 
 
 
 
 
 
H ol d  o n  Or der  is release d, a n d dr u g  
is s hi p pe d t o partici pa nt  
 
 
X 
 
 
 
 
 
St u d y  I nstr ucti o ns 
 
 
X  
 
 
 
 
 
e Diar y I nstr ucti o ns 
 
 
X  
 
 
 
 
 
A E re p orti n g 
 
 
X  
 
X  
X  
X  
X  
Re or der d  
 
 
 
 
 
 
 
Partici pa nt  c o m pletes Virt ual Visit  2  
 
 
 
 
 
X  
 
Ce ntral  Assess or  c o nfir ms verifie d 
L D L - C. Visit t o be resc he d ule d  if 
verifie d n u m bers are  n ot pr o vi de d.  
 
 
 
 
 
 
 
X 
 
Partici pa nt  c o m pletes fi nal T A S S  
assess me nt e 
 
 
 
 
 
 
X 
 
C o nfir m  me dical  a n d me dicati o n 
hist or y c ha n ges c 
 
 
 
 
 
 
X 
 
Diar y  re vie w f or A Es f 
 
 
 
 
X 
X 
X 
 
F oll o w -u p  o n  i nc orrect T A S S  
e ntries a n d use  
 
 
X
i 
 
 
 
X
j 
 
Dr u g  Acc o u nta bilit y  
 
 
 
 
 
 
X  
 

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a 
Dr u g  will  n ot  be  s hi p pe d u ntil  “ O K t o Use”  partici pa nt  c o m pletes  Virt ual  Visit  1 a n d t he y are c o nfir me d  t o e nter H o me  Use Peri o d.  
b 
La b a n d B P  res ults m ust be wit hi n 1 2 m o nt hs ( + 3 m o nt h wi n d o w) of c o m pleti n g t he We b A p p a n d be a ble t o i de ntif y na me of partici pa nt  i n or der t o be c o nsi dere d verifie d f or 
Virt ual  Visit  1.  If partici pa nt  d oes  n ot  ha ve  verifie d  la b test, t he y will  be  se nt f or st u d y ma n date d  testi n g pri or  t o c o m pleti n g  Virt ual  Visit 1  w hic h  will t he n  be  c o nsi dere d  as 
verifie d  s o urce.  L D L-C res ults  m ust N O T be  pri or t o Crest or O T C start date f or Virt ual  Visit  2.  F or partici pa nts w h o wit h dra w,  disc o nti n ue fr o m st u d y i nter ve nti o n or t h ose 
w h o recei ve d a “ D o N ot  Use” o utc o me or a n “ As k a D oct or” o utc o me  a n d ne ver c o nfir me d t he y s p o ke t o a d oct or,  st u d y ma n date d testi n g will n ot be perf or me d.  F or males 
a ge 2 0 t o 3 9,  a s o urce verifie d bl o o d press ure ( B P) will n ot  be re q uire d si nce B P d oes n ot  fact or i nt o t he use assess me nt base d o n c urre nt g ui deli nes. 
c 
O nce  t he me dical  assess me nt is c o m plete; t he C M O G  cli nicia n  will  use  t he data  o btai ne d  i n t he me dical  assess me nt a n d t he n i n p ut t hat data  i nt o t he We b  A p p.  
d 
Re or ders  s hi p pe d t o partici pa nt  if a p pr o ve d  f or dis pe nsi n g  t hr o u g h T A S S re or der  assess me nt  i n We b  A p p.  
e 
O nl y  partici pa nts  w h o,  at t heir last or der,  recei ve d a n “ O K t o Use”  or  “ As k a D oct or”  (a n d i n dicate d t he d oct or  sai d it was  O K  t o Use Crest or)  will  c o m plete a T A S S  fi nal use  
assess me nt at Virt ual  Visit  2. 
f 
T he diar y  will  be  re vie we d b y  t he C M O G  f or A Es at t he da y  6 0  a n d da y  1 2 0  p h o ne  call a n d at t he Virt ual  Visit  2.  T he  diar y  will be  use d  t o rec or d w he n  t he partici pa nt  t o o k 
st u d y dr u g,  if t he y ha ve  c ha n ges  t o a n y me dicati o ns,  a n d if t he y ha ve  a n y c ha n ges  i n healt h  stat us.  T he diar y  will  als o be  use d  f or t he partici pa nt  t o rec or d t he u ni q ue  b ottle  I D 
n u m ber  t o c o nfir m  recei pt of  deli ver y  of  t he st u d y dr u g.  
g 
I nteri m p h o nes  calls c o nsist of  a tele p h o ne stat us  c hec k o n partici pa nts  t o assess a n y c ha n ges  i n healt h a n d/ or  me dicati o ns  as well  as a n y a d diti o nal st u d y-relate d iss ues. At  
a p pr o xi matel y Da y 1 6 5,  t he partici pa nt’s Virt ual Visit 2 will als o be sc he d ule d.  
h 
T he o nl y  la b val ue  verifie d  at t he Fi nal  Virt ual  Visit is  L D L -C.  
i 
F oll o w -u p  pr o bes  t o u n dersta n d  t he rati o nale f or a n y discre pa ncies  bet wee n  t he partici pa nt  a n d C M O G  T A S S e ntries will  be  as ke d  of  a n y T A S S  q uesti o n  t hat is o nl y  as ke d  at 
i nitial self-selecti o n assess me nt as well as partici pa nts w h o d o n ot meet t he criteria f or pr ocee di n g i nt o t he use p orti o n of t he st u d y at Virt ual V isit 1. 
j 
F oll o w -u p  pr o bes  t o u n dersta n d  t he rati o nale f or a n y discre pa ncies  bet wee n  partici pa nt  a n d C M O G  T A S S e ntries  will  be  as ke d  f or all fi nal use assess me nts  as well  as a n y 
re mai ni n g discre pa ncies  fr o m t he i nitial self-selecti o n assess me nt t hat were  n ot  as ke d  at Virt ual  Visit  1.  
k 
N ote  t hat + 1 4 -da y  visit  wi n d o w  e xte n ds  t he 3 0 -da y  peri o d  (t o 4 4  t otal da ys)  a n d i ncl u des partici pa nt  c o m pleti o n  of  t he Pre -scree n p h o ne  call, self-selecti o n, a n d Virt ual  Visit 1.  
l 
S u bjects  will  eit her  call t he Call Ce nter  f or pre -scree ni n g or  a n o nli ne  pre -scree ner will  als o be  a vaila ble. If t he o nli ne  pre -scree ner is c o m plete d  a n d t he s u bject q ualifies,  t he y 
will  be  directe d  t o call t he Call Ce nter or t he Call Ce nter will i nitiate a n o ut b o u n d call t o pr o vi de t he e mail li n k. 
m  
If at Virt ual  Visit  1 or  Virt ual  Visit  2, t he  pre g na nc y  test has  a n i nc o ncl usi ve res ult, t he partici pa nt  will  be  resc he d ule d i n 2 t o 4 wee ks  at w hic h  ti me t he uri ne  pre g na nc y  test 
will  be  re peate d. 
 
 

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2  
I N T R O D U C TI O N 
Crest or 5  m g  is a safe a n d hi g hl y effecti ve  m o derate -i nte nsit y d ose of r os u vastati n calci u m t o 
l o wer c h olester ol, o ne of t he ke y ris k fact ors t hat ca n lea d t o heart disease. 
2. 1  
St u d y  R ati o n ale  
T he  partial  s witc h of Crest or  5 m g  w o ul d re prese nt t he first stati n pr o d uct a vaila ble wit h o ut a 
prescri pti o n t o l o wer c h olester ol i n c o ns u mers w h o ha ve a m o derate ris k of heart disease.  
T he  O ver -t he- C o u nter ( O T C) a vaila bilit y of Crest or  5 m g w o ul d pr o vi de a n i m p orta nt ne w 
o pti o n t o self -treat hi g h c h olester ol. 
T his pi v otal Self -Selecti o n ( S S) a n d Act ual Use St u d y ( A U S) is i nte n de d t o e val uate t he use 
of r os u vastati n 5 m g i n c o m bi nati o n wit h a S oft ware as a Me dical De vice ( Sa M D) ( We b  A p p 
t hat feat ures a Tec h n ol o g y-Assiste d Self -Selecti o n [ T A S S] t o ol). S pecificall y, t he e xte nt  t o 
w hic h partici pa nts ca n safel y a n d effecti vel y  self-select, p urc hase, a n d f oll o w a 6- m o nt h 
re gi me n of Crest or 5 m g acc or di n g t o t he Dr u g Facts La bel ( D F L) i n a n u ns u per vise d 
e n vir o n me nt. A C o ns u m er I nf or mati o n Leaflet ( CI L) will als o be pr o vi de d as s u p p orti ve 
i nf or mati o n. T he T A S S  t o ol acts as a di gitize d, i nteracti ve versi o n of  t he D F L, all o wi n g 
partici pa nts t o a ns wer a d y na mic a n d pers o nalize d set of healt h -relate d q uesti o ns, i n lie u of 
br o wsi n g/searc hi n g a D F L  f or i nf or mati o n perti ne nt t o t he m. D uri n g t he ( u ns u per vise d) use 
peri o d, partici pa nt c o m plia nce  a n d a d here nce will be e val uate d, i ncl u di n g o n g oi n g use of t he 
We b  A p p t o re p ort c ha n ges i n healt h stat us, deter mi ne t he c o nti n ue d s uita bilit y of  t he 
me dici ne,  a n d p urc hase a d diti o nal s u p pl y. T o  test o ur e C o m merce  a p pr oac h, t he A U S will 
mi mic, as m uc h as p ossi ble i n a cli nical trial, t he i n -mar ket setti n g.  
2. 2  
B ac k gr o u n d  
Heart  disease re mai ns  t he lea di n g ca use of deat h  f or b ot h me n  a n d w o me n  i n t he U nite d  States 
a n d w orl d wi de. Ele vate d c h olester ol is a maj or ris k fact or f or heart disease, a n d w hile 
l o weri n g c h olester ol wit h stati n dr u gs re d uces car di o vasc ular m or bi dit y a n d m ortalit y, o nl y 
a b o ut half of t he pe o ple i n t he U nite d States w h o re q uire t hera p y are treate d (Merca d o et al 
2 0 1 5 ). T here are n u mer o us reas o ns f or t he i nertia i n getti n g pe o ple treate d. W hat is clear is 
easier access t o safe, effecti ve, a n d aff or da ble t hera p y w o ul d ha ve a si g nifica nt p ositi ve 
i m pact o n p u blic healt h. O ne  wa y t o si m plif y access  t o stati n t hera p y w o ul d be t o ma ke  t he m 
“ O T C.” W hile  atte m pts were  ma de  i n t he past t o  s witc h stati ns O T C, t he st u dies faile d d ue t o 
c o ncer ns a b o ut t he efficac y of t he stati ns t hat were  teste d a n d beca use c o ns u mers were u na ble 
t o pr o perl y self-select. T he Crest or O T C pr o gra m a d dresses t hese t w o c o ncer ns b y usi n g 
Crest or 5 m g  (a safe a n d hi g hl y effecti ve d ose of r os u vastati n wit h mi ni mal i nteracti o ns) a n d a 
T A S S t o ol t hat  e ns ures pr o per self -selecti o n.  C o m plete d st u dies testi n g D F L c o m pre he nsi o n, 
CI L c o m pre he nsi o n, We b A p p c o m pre he nsi o n, H u ma n Fact ors, Tar gete d Self- Selecti o n a n d 
All -c o mers Self - Selecti o n ha ve s h o w n t hat t his a p pr oac h is via ble.  Base d o n t he p ositi ve 

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res ults fr o m t hese pi v otal st u dies, Astra Ze neca is rea d y t o pr ocee d wit h t he  A U S.  A detaile d 
descri pti o n  of t he c he mistr y,  p har mac ol o g y, efficac y, a n d safet y of Crest or 5 m g is pr o vi de d i n 
t he prescri pti o n  ( R x) U nite d  States  Prescri bi n g  I nf or mati o n ( U S PI) (Astra Ze neca 
P har mace uticals L P 2 0 2 1 ). 
2. 3  
Be nefit/ Ris k  Assess me nt  
M ore detaile d i nf or mati o n  a b o ut t he k n o w n a n d e x pecte d be nefits  a n d p ote ntial ris ks of 
Crest or 5 m g ma y be f o u n d i n t he Crest or R x U S P I (Astra Ze neca P har mace uticals L P 2 0 2 1 ). 
2. 3. 1  
Ris k  Assess me nt  
T he o verall safet y pr ofile of r os u vastati n calci u m ( 5 – 4 0 m g) was esta blis he d i n a lar ge 
cli nical trial pr o gra m t hat i ncl u de d o ver 1 2, 0 0 0 patie nts, m ulti ple lar ge car di o vasc ular ( C V) 
o utc o me trials, a n d a p ost mar keti n g e x perie nce i n o ver 2 0 0 milli o n patie nts w orl d wi de 
(Y us uf et al 2 0 1 6 , Ri d ker et al 2 0 0 8 ). Overall, Crest or was well t olerate d.   T he m ost 
c o m m o nl y re p orte d a d verse e ve nts ( A Es) i n c o ntr olle d cli nical trials were  hea dac he,  m yal gia,  
a b d o mi nal pai n,  ast he nia a n d na usea.  M ost si de effects were mil d t o m o derate i n i nte nsit y a n d  
di d n ot lea d t o disc o nti n uati o n. A d verse e ve nts wit h Crest or t hat are part of t he War ni n gs a n d 
Preca uti o ns i n t he Crest or R x U S PI i ncl u de t he f oll o wi n g: s keletal m uscle effects (i.e., 
m y o pat h y a n d r ha b d o m y ol ysis), li ver e nz y me a b n or malities, dr u g i nteracti o n wit h c o u ma di n 
a ntic oa g ula nts, pr otei n uria a n d he mat uria a n d e n d ocri ne effects.  All of t hese a d verse effects 
are d ose relate d wit h a l o w fre q ue nc y of o bser ve d e ve nts at t he 5 m g d ose  (Astra Ze neca 
P har mace uticals L P 2 0 2 1 ).  
N o n prescri pti o n  r os u vastati n is a dru g - de vice c o m bi nati o n  pr o d uct c o m prise d of r os u vastati n 5 
m g a n d a We b  A p p. T he  We b  A p p hel ps t o e ns ure pr o per self-selecti o n d uri n g t he i nitial 
p urc hase a n d re or der pr ocess  b y ha vi n g t he c o ns u mer a ns wer a series  of  q uesti o ns t hat e ns ure 
c o m plia nce wit h t he D F L a n d 2 0 1 8 G ui deli ne o n t he Ma na ge me nt of Bl o o d C h olester ol 
(Gr u n d y et al 2 0 1 8 ). C o ns u mers wit h a n y e xisti n g c o n diti o ns t hat c o ul d res ult i n a n i ncrease d 
ris k f or A Es are eit her e xcl u de d fr o m treat me nt or t ol d t o “ As k a D oct or” bef ore t he y ca n 
or der dr u g o nli ne. 
B y usi n g t he We b  A p p, t he p ote ntial f or A Es wit h r os u vastati n 5 m g is si g nifica ntl y re d uce d, 
b ut n ot eli mi nate d. 
 
T heref ore, t he p ote ntial f or a s o ft ware err or res ulti n g i n a partici pa nt w h o has a 
c o ntrai n dicati o n t o t hera p y accessi n g dr u g is ver y l o w (e. g., pre g na nt w o ma n or w o ma n w h o 
is breastfee di n g).  W hile  s oft ware err ors lea di n g t o A Es  are u nli kel y, s o me o ne c o ul d a ns wer 
o ne of t he We b A p p q uesti o ns i nc orrectl y lea di n g t o i na p pr o priate access t o t hera p y. 
T he  pri mar y  e n d p oi nt of  t his st u d y will  all o w us t he o p p ort u nit y t o better  u n dersta n d t he 
fre q ue nc y of e ntr y err ors lea di n g t o i na p pr o priate access t o t hera p y. 
C CI

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I n t his A U S,  we  will  m o nit or  f or all dr u g a n d de vice A Es.  I n a d diti o n, a n e mail will be 
tri g gere d via t he We b  A p p t o t he C o ntract Researc h Or ga nizati o n ( C R O) if t he partici pa nt 
i n dicates d uri n g re or der t hat t he y are pre g na nt, ha d a C V e ve nt, i ncrease d l o w- de nsit y 
li p o pr otei n-c h olester ol ( L D L -C), ne w m uscle s y m pt o ms, li ver disease  a n d ki d ne y disease  (see 
Secti o n  8. 4. 4  a n d Secti o n  1 0  f or f urt her details). T hese fi n di n gs are e x pecte d t o be ver y rare 
d uri n g t he c o urse of t his st u d y. 
O verall,  t he ris k t o partici pa nts  fr o m eit her t he dr u g or t he de vice i n t his A U S  is ver y l o w. T he 
pr oce d ures u n derta ke n i n t he pr ot oc ol will hel p t o e ns ure t he safet y of partici pa nts e nr olle d i n 
t his st u d y. 
2. 3. 2  
Be nefit  Assess me nt   
I n a d diti o n t o ha vi n g a well -t olerate d safet y pr ofile, r os u vastati n 5 m g is  hi g hl y efficaci o us. I n  
a 6-wee k,  d o u ble- bli n d, place b o -c o ntr olle d st u d y, r os u vastati n 5 m g  l o were d l o w- de nsit y 
li p o pr otei n-c h olester ol ( L D L - C) b y 4 5 % (Astra Ze neca P har mace uticals L P 2 0 2 1 ). Base d o n 
t he Crest or R x U S PI f or i n di vi d ual stati ns  a vaila ble i n t he U nite d  States, t he  re d ucti o n i n 
L D L - C wit h r os u vastati n 5 m g is  si milar or greater t ha n t hat re p orte d f or ot her stati ns t hat 
re prese nt a p pr o xi matel y 7 0 % of all stati n prescri pti o ns i n t he U nite d States t o da y (I M S data). 
I n t he 6- wee k st u d y, r os u vastati n als o s h o we d be nefits o n ot her i m p orta nt li pi d para meters. 
T otal C h olester ol ( T C), n o n - hi g h- de nsit y li p o pr otei n-c h olester ol ( n o n-H D L - C), A p o B a n d 
Tri gl yceri des were re d uce d b y 3 3 %, 4 4 %, 3 8 % a n d 3 5 %, res p ecti vel y. H D L -C was i ncrease d 
b y 1 3 %. T he be nefits o n Tri gl yceri des a n d  H D L - C are i m p orta nt si nce ma n y  pe o ple wit h  
a b n or mal L D L - C le vels als o ha ve a b n or mal Tri gl yceri de a n d H D L-C le vels.   T he be nefits of 
r os u vastati n 5 m g o n L D L- C a n d ot her li pi d para meters  has bee n o bser ve d i n n u mer o us 
cli nical trials e val uati n g s h ort  s h ort-ter m a n d l o n g- ter m treat me nt. 
W hile t he be nefits of r os u vastati n 5 m g o n car di o vasc ular m or bi dit y a n d m ortalit y has n ot 
bee n s pecificall y e val uate d i n a n o utc o me st u d y, r os u vastati n 1 0 m g a n d 2 0 m g ha ve bee n 
st u die d i n t he H O P E- 3 (Y us uf et al 2 0 1 6 ) a n d J U PI T E R  (Ri d ker et al 2 0 0 8 ) trials, 
res pecti vel y.  B ot h of t hese trials e nr olle d a pri mar y pre ve nti o n patie nt p o p ulati o n.  I n 
H O P E - 3, r os u vastati n 1 0 m g re d uce d b ot h c o- pri mar y e n d p oi nts.  F or t he c o m bi ne d e n d p oi nt 
of C V deat h, m y ocar dial i nfarcti o n ( MI) a n d str o ke, t he Hazar d Rati o ( H R) was 0. 7 6 ( CI: 0. 6 4 
– 0. 9 1, P = 0. 0 0 2). F or t he  c o-pri mar y  e n d p oi nt of C V  deat h, MI,  str o ke, res uscitate d car diac 
arrest, heart  fail ure a n d re vasc ularizati o n, t he H R was 0. 7 5 ( CI: 0. 6 4 – 0. 8 8, p < 0. 0 0 1) (Y us uf 
et al 2 0 1 6). I n t he J U PI T E R Trial, r os u vastati n 2 0 m g re d uce d t he c o m bi ne d e n d p oi nt of MI, 
str o ke, arterial re vasc ularizati o n, h os pitalizati o n f or u nsta ble a n gi na or C V deat h. T he H R 
was 0. 5 6 ( CI 0. 4 6 – 0. 6 9, p < 0. 0 0 0 0 1) (Ri d ker et al 2 0 0 8 ). I m p orta ntl y, w hile  the 5 m g  d ose 
was  n ot e val uate d  i n a n o utc o me trial, t he L D L -l o weri n g effects of r os u vastati n 5 m g are 
si milar t o or greater t ha n  t he L D L-l o weri n g effects see n i n la n d mar k stati n trials t hat 
de m o nstrate d be nefit i n pri mar y a n d sec o n dar y pre ve nti o n c o n d ucte d o ver t he last 2 deca des 
(Fa b bri a n d Ma g gi o ni 2 0 0 9 ). Base d o n t he data fr o m la n d mar k stati n trials, H O P E- 3 a n d 

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J U PI T E R, r os u vastati n 5 m g w o ul d be e x pecte d t o ha ve a si g nifica nt be nefit o n C V m or bi dit y 
a n d m ortalit y. 
2. 3. 3  
O ver all  Be nefit: Ris k  C o nc l usi o n 
T he o verall assess me nt of be nefit a n d ris k f or r os u vastati n 5 m g w o ul d s u p p ort its use as a 
n o n prescri pti o n me dici ne  t o l o wer c h olester ol, a n d  its e val uati o n i n t his A U S.  T he  5 m g  d ose 
is hi g hl y efficaci o us i n l o weri n g L D L- C a n d base d o n t he pre p o n dera nce of e vi de nce w o ul d 
be e x pecte d t o s h o w a be nefit i n re d uci n g C V m or bi dit y a n d m ortalit y. W hile n o me dici ne is 
wit h o ut ris k, r os u vastati n 5 m g has a n e xcelle nt safet y pr ofile. It has a l o w i nci de nce of A Es, 
its meta b olis m is n ot de pe n de nt o n c yt oc hr o me P 4 5 0 t h us mi ni mizi n g t he p ote ntial f or dr u g-
dr u g i nteracti o ns, a n d it has n o k n o w n mis use a n d a b use p ote ntial. 
A d diti o nall y,  t he p ote ntial f or seri o us A Es  s h o ul d be mi ni mize d  b y use of  t he We b A p p, w hic h 
de- selects pe o ple w h o mi g ht be at hi g her ris k f or seri o us A Es. 

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O bjecti ves  
E n d p oi nts  
A n al ysis P o p ul ati o n  
( See Section 
9.3_ b o o k mar k 7 8  f or 
defi niti o ns)  
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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O bjecti ves  
E n d p oi nts  
A n al ysis P o p ul ati o n  
( See Section 
9.3_ b o o k mar k 7 8  f or 
defi niti o ns)  
•  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3. 1  
E n d p oi nt  R ati o n ale  
T he first c o -pri mar y e n d p oi nt f or t his st u d y e val uates c orrect i nitial self -selecti o n i n 
partici pa nts w h o ulti matel y recei ve d a n “ O K t o Use” o utc o me usi n g t he T A S S t o ol 
tec h n ol o g y. W hile  t he All-C o mers Self -Selecti o n  pi v otal st u d y was desi g ne d t o s h o w t hat t he 
We b A p p c o ul d s uccessf ull y e xcl u de partici pa nts  w h o were  n ot a p pr o priate f or treat ment, 
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(i.e., 9 2 % of partici pa nts ha d a “ N ot Ri g ht f or Y o u” o utc o me, w hic h e q uates t o a “ D o N ot 
Use” i n t he A U S), t he A U S will o nl y e nr oll partici pa nts w h o o btai n a n “ O K t o Use” o utc o me 
or a n “ As k  a D oct or” o utc o me a n d i n dicate t he d oct or ga ve  t he m per missi o n  t o use 
n o n prescri pti o n r os u vastati n. Beca use “c orrect selecti o n” is t he critical starti n g p oi nt f or 
treat me nt, t he first pri mar y e n d p oi nt i n t he A U S  will  e val uate t he a bilit y of partici pa nts  t o 
c orrectl y  select Crest or O T C f or i nitial use.  
T he sec o n d c o- pri mar y e n d p oi nt is a “ use” e n d p oi nt a n d e val uates w het her partici pa nts are 
pr o perl y usi n g n o n prescri pti o n r os u vastati n d uri n g t he use peri o d as assesse d b y t heir a bilit y 
t o c orrectl y  i de ntif y c ha n ges  i n t heir healt h stat us t hr o u g h use of t he We b  A p p  or b y ta ki n g a n 
acti o n t hat c o m plies wit h t he D F L. T his e n d p oi nt is a re- e val uati o n of a partici pa nt’s healt h 
stat us n ot t y picall y c o n d ucte d i n ot her R x-t o-O T C s witc h pr o gra ms.   Pri or t o e ver y re or der, 
partici pa nts are re q uire d  t o e nter t he We b A p p a n d ta ke a n a b bre viate d me dical assess me nt t o 
e ns ure t hat t he y ha ve n ot ha d a c ha n ge i n t heir healt h stat us.  D uri n g t his re or der assess me nt, 
partici pa nts are as ke d a b o ut c ha n ges i n t heir me dical a n d me dicati o n hist or y t hat w o ul d 
re q uire t he m t o st o p use a nd/ or s pea k t o a d oct or. T he y  are als o as ke d a b o ut t heir re peat L D L - 
C test a n d t o i n p ut t heir n u m ber t o e ns ure t he y are getti n g a n a de q uate t hera pe utic res p o nse. 
T heir res p o nses will res ult i n o ne of t hree o utc o mes, “ O K t o Use,” “ D o N ot Use,” or “ As k a 
D oct or.”  A “ D o N ot  Use”  o utc o me will  res ult w he n  t he partici pa nt e nters i nf or mati o n i nt o t he 
a p p t hat i n dicates t he y met t he Pre g n a ncy Alert, D o N ot Use, or St o p Use c o n diti o ns liste d i n 
t he D F L. T he y will als o recei ve a “ D o N ot Use” o utc o me if t heir L D L - C retest s h o ws a n 
i ncrease i n t he L D L-C or t he y e nter t w o L D L -C retest res ults t hat de m o nstrate a n i na de q uate 
res p o nse (i.e., ≥ 0 % a n d <  1 5 % re d ucti o n). F or i na de q uate res p o nses, t he partici pa nt is 
i nstr ucte d t hr o u g h t he We b A p p a n d tra nsacti o nal e mails t o retest wit hi n 3 m o nt hs. N ote t hat 
t he We b A p p i nstr ucts pe o ple wit h a n i nitial i na de q uate res p o nse t o ta ke o ne of t he f oll o wi n g 
acti o ns: 
•  
If t he partici pa nt has bee n  c o m plia nt  wit h  d osi n g, t he y are i nstr ucte d t o see a d oct or.  
•  
If t he partici pa nt  has N O T  bee n  c o m plia nt wit h  d osi n g, t he y are i nstr ucte d t o be c o m plia nt 
a n d t o retest wit hi n 3 m o nt hs. 
 
Partici pa nts  w h o  ha ve n o c ha n ge or a n  i ncrease i n L D L - C will  be i m me diatel y st o p pe d fr o m 
re p urc hasi n g dr u g. T hese i n di vi d uals will n ot be eli gi ble f or a retest. 
T he a bilit y t o le vera ge tec h n ol o g y t o re- assess c o ns u mers at t he ti me of eac h p urc hase is 
u n prece de nte d  i n t he c urre nt O T C  e n vir o n me nt a n d offers  a n i m p orta nt safet y c hec k t o e ns ure 
t hat t he ke y re q uire me nts f or c o nti n ue d use are met. 
Beca use of t h e i m p orta nce of t he first c o -pri mar y e n d p oi nt i n esta blis hi n g t hat Crest or O T C 
ca n be c orrectl y self -selecte d a n d t he sec o n d c o- pri mar y e n d p oi nt s h o wi n g a p pr o priate use 

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wit h o ut t he o versi g ht of a healt hcare pr o vi der, t he t hres h ol d f or s uccess f or b ot h was set at a 
p oi nt esti mate of 9 0 % wit h a l o wer b o u n d of 8 5 %. Meeti n g t his ri g or o us t hres h ol d will 
pr o vi de a hi g h le vel of  c o nfi de nce t hat t he ri g ht c o ns u mers will  be a ble t o pr o perl y self-select 
a n d use Crest or O T C w he n it is a vaila ble wit h o ut a prescri pti o n.  
T he t hir d  c o-pri mar y e n d p oi nt was selecte d t o e val uate t he L D L -C efficac y of r os u vastati n 
5 m g. Efficac y i n  l o weri n g L D L-C will be e val uate d as mea n perce nt c ha n ge fr o m baseli ne i n 
verifie d L D L -C at Visit 2.  F or t he p ur p oses of t he statistica l e val uati o n of t his e n d p oi nt, t he 
u p per b o u n d of t he 9 5 % c o nfi de nce i nter val o n t he mea n perce nt c ha n ge fr o m baseli ne 
( P C F B) i n t he o verall a nal ysis nee ds t o be less t ha n -1 5 % a n d t he p oi nt esti mate nee ds t o be 
less t ha n or e q ual t o -2 0 %.  T hese t hres h ol ds  were c h ose n base d o n se veral fact ors:  1) 2 0 1 8 
A H A/ A C C  g ui deli nes w hic h state  t hat i n i nter me diate ris k ( ≥ 7. 5 % t o < 2 0 % 1 0-year 
at her oscler otic car di o vasc ular disease [ A S C V D] ris k) patie nts, L D L -C le vels nee d t o be 
re d uce d b y 3 0 % or m ore, 2) real w orl d cli nical practice res ults s h o w t hat a 2 0 % or greater 
re d ucti o n i n L D L-C is a realistic, ac hie va ble g oal f or 5 m g r os u vastati n i n a real w orl d setti n g 
(B ulla n o et al 2 0 0 6 , F o x et al 2 0 0 7 ) a n d 3) p ote ntial p u blic healt h be nefits f or patie nts at 
i ncrease d C V ris k w h o are n ot c urre ntl y  o n a n y L D L-l o weri n g t hera p y.  Alt h o u g h a n  L D L - C 
l o weri n g treat me nt effect of  1 5 % t o < 3 0 % is  s u b o pti mal acc or di n g t o t he g ui deli nes, t he be nefits 
of t hera p y o ut wei g h  t he ris ks a n d pr o vi de a n o p p ort u nit y f or re peate d messa gi n g t o t he 
c o ns u mer t o i m pr o ve t heir c o m plia nce wit h me dicati o n or t o f oll o w - u p wit h a healt h care 
pr o vi der t o o pti mize t hera p y.  
T he  sec o n dar y e n d p oi nts were  selecte d t o e val uate c o m plia nce wit h  retest re q uire me nts, 
c o m plia nce wit h la be l war ni n gs a n d c o m plia nce wit h d osi n g. 
T he L D L -C retest s uccess t hres h ol d was set at 6 0 %.  I n t he at or vastati n A U S, c o m plia nce 
wit h L D L - C retesti n g was 6. 7 % bet wee n wee ks 2 a n d 1 2 a n d 5 2 % o ver t he c o urse of t he 
st u d y.  I n t he l o vastati n A U S, c o m plia nce wit h retesti n g was 7 1 % o ver t he c o urse of t he st u d y 
(Pfizer I nc 2 0 1 6 , Meli n et al 2 0 0 4 ). T o better u n dersta n d t he res ults fr o m t hese st u dies, 
Astra Ze neca c o m missi o ne d A E TI O N ®  t o c o n d uct a st u d y usi n g Pr o g n os Healt h a n d I B M 
Mar ket Sca n data t o deter mi ne t he fre q ue nc y of L D L- C retesti n g i n patie nts w h o i nitiate d 
t hera p y wit h a prescri pti o n stati n (refer t o A p pe n di x D ). Of  t he 1. 2 M patie nts i n t his dataset, 
2 5 % ha d a retest wit hi n  3 m o nt hs, 5 0 % wit hi n 6 m o nt hs a n d 7 5 % wit hi n 1 2 m o nt hs. T hese 
data s u g gest t hat t he at or vastati n res ults are i n li ne wit h t he  data fr o m prescri pti o n  stati ns 
w hile t he Merc k data was hi g her a n d m ost li kel y d ue t o t heir use of a n o pti o nal Me vac or O T C 
Self -Ma na ge me nt S yste m ( M O T C - S M S).  W hile all c ust o mers i n o ur pr o gra m will recei ve 
tra nsacti o nal e mails t o hel p e ns ure c o m plia nce wit h retesti n g, t he ulti mate i m pact of t hese 
e mails is u n k n o w n.  T heref ore, t he 6 0 % t hres h ol d was  set as t he mi ni m u m  val ue i n t his st u d y 
beca use  retesti n g f or Crest or O T C s h o ul d be at least as g o o d as or better t ha n what is  o bser ve d 
c urre ntl y i n t he real w orl d wit h stati n t hera p y.  

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Sec o n dar y e n d p oi nts were esta blis he d t o assess c o m plia nce wit h eac h s pecific t y pe of D F L 
war ni n g. F or t hese e n d p oi nts, partici pa nts will be e val uate d f or t heir a bilit y t o f oll o w t he 
war ni n gs base d o n c orrectl y e nteri n g t he i nf or mati o n i nt o t he We b A p p, w hic h w o ul d pre ve nt 
a re or der fr o m occ urri n g, or base d o n t he fact t hat t he y st o p pe d t hera p y (re gar dless of w het her 
t he y use d t he We b A p p). Si nce t hese sit uati o ns are li kel y t o be l o w fre q ue nc y e ve nts, n o 
defi niti ve s uccess t hres h ol ds were esta blis he d f or t hese e val uati o ns.  
O verall c o m plia nce wit h d osi n g will be  assesse d usi n g t hree met h o ds: pill c o u nt, diar y re vie w 
a n d n u m ber of re or ders usi n g t he We b A p p. T he  first assess me nt f or o verall c o m plia nce uses 
t he pill c o u nt or e Diar y. Eac h partici pa nt will ha ve o verall c o m plia nce assesse d a n d will be 
c o nsi dere d s uccessf ull y c o m plia nt wit h d osi n g if t he y t o o k bet wee n 5 0 % a n d 1 2 0 % of t heir 
pills.  T he  tar get t hres h ol d f or t he o verall c o m plia nce e n d p oi nt is a n o bser ve d p oi nt esti mate 
f or t he perce nta ge of partici pa nts falli n g i n t he 5 0- 1 2 0 % ra n ge t o be at least 5 0 %. I n ot her 
w or ds, at least half of t he partici pa nts nee d t o be s uccessf ull y c o m plia nt wit h d osi n g. I n 
a d diti o n t o o verall c o m plia nce, a l o n git u di nal c o m plia nce rate will be calc ulate d t o assess 
c o m plia nce wit h c o nti n u o us d osi n g acr oss eac h st u d y dr u g re or der s u p pl y peri o d. T he pill use 
f or t his a nal ysis will c o me fr o m t he e Diar y. Fi nall y, a n a d diti o nal assess me nt of l o n git u di nal 
c o m plia nce/ persiste nce will be perf or me d usi n g re or der data fr o m t he We b A p p.  T his 
e n d p oi nt will e val uate t he perce nta ge of users w h o were eli gi ble f or c o nti n u o us treat me nt a n d 
or dere d 1 8 0 da ys of t hera p y. T o be eli gi ble f or c o nti n u o us treat me nt, t he partici pa nts m ust 
ha ve recei ve d a n “ O K t o Use” o utc o me or a n “ As k  a D oct or” o utc o me a n d i n dicate t he  d oct or 
ga ve t he m per missi o n t o c o nti n ue treat me nt, a n d t he y c o nti n ue d t o ha ve o ne of t hese 
o utc o mes at all assess me nts (i nitial, re or der a n d fi nal use). Partici pa nts w h o disc o nti n ue or 
wit h dra w are n ot eli gi ble  f or c o nti n u o us treat me nt. S uccess is persiste nce ≥5 0 % si milar t o t he 
ot her c o m plia nce/ persiste nce e n d p oi nts.  T he rati o nale f or setti n g t he c o m plia nce/ persiste nce 
t hres h ol ds at 5 0 % is base d o n prescri pti o n data w hic h s h o ws t hat after 1 8 0 da ys o nl y a b o ut 
4 4 % of pe o ple c o nti n ue t o refill t heir prescri pti o ns. O ur i nte nti o n  is t o s h o w t hat o ur a p pr oac h 
will be at least as g o o d, if n ot better, o n c o m plia nce a n d persiste nce t ha n w hat is o bser ve d i n 
t he real w orl d  (I Q VI A). A d diti o nall y, ass u mi n g a n i n di vi d ual ta kes t he me dici ne 
i nter mitte ntl y f or t he d urati o n of t he st u d y, a 5 0 % d osi n g c o m plia nce w o ul d e q uate t o ta ki n g a 
2. 5 m g d ose of r os u vastati n c o m pare d t o a 5 m g d ose.  Base d o n t he cli nical trial  data, a 2. 5 
m g d ose gi ves a n L D L- C l o weri n g of a p pr o xi matel y 3 5 % (Olss o n et al 2 0 0 1 ). T heref ore, 
s o me o ne ta ki n g r o u g hl y half of t heir pills (e. g., a 4 5- pill c o u nt ta kes a b o ut 9 0 da ys t o use) 
w o ul d still recei ve e xcelle nt efficac y.  
W hile  d osi n g c o m plia nce  will  be assesse d,  t he best  meas ures  f or s uccessf ul c o m plia nce  will be  
t he L D L - C l o weri n g ac hie ve d b y partici pa nts i n t he st u d y a n d t he n u m ber of partici pa nts w h o 
c o nti n ue t o re or der.  
F oll o wi n g fr o m t he sec o n dar y e n d p oi nts re gar di n g c o m plia nce wit h use war ni n gs, se veral 
 
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S T U D Y  D E SI G N  
4. 1  
O ver all  Desi g n  
T his is a 6 - m o nt h, si n gle-ar m, i nter ve nti o nal, p hase III S S a n d A U S usi n g a T A S S t o ol wit hi n 
a We b  A p p. It is a n o pe n-la bel st u d y usi n g n o n- prescri pti o n r os u vastati n 5 m g i n partici pa nts 
w h o q ualif y f or treat me nt base d o n t he me dical a n d me dicati o n hist or y, la b orat or y a n d bl o o d 
press ure ( B P) data t he y e nter i nt o t he We b  A p p.  T he st u d y will e nr oll  a p pr o xi matel y 1, 2 2 0 
partici pa nts  w h o will ulti matel y recei ve  a n “ O K t o Use” o utc o me usi n g t he We b  A p p.  Of  
t hese, a n esti mate d 1, 0 0 0 partici pa nts  will  ulti matel y  pr ocee d t o t he use p hase.  N ote t hat s o me 
i n di vi d uals ma y i nitiall y get a n “ As k a D oct or” o utc o me beca use of a p ote ntial iss ue wit h 
treat me nt i de ntifie d f oll o wi n g t he T A S S assess me nt.   If t he y as k a d oct or a b o ut t he p ote ntial 
iss ue, a n d t he d oct or gi ves t he m per missi o n t o or der dr u g,  t he y ca n g o bac k i nt o t he a p p a n d 
reta ke t he T A S S  assess me nt.   W he n t he y c o nfir m t he d oct or has gi ve n per missi o n, t he y will be 
a ble t o pr ocee d t o t he use p hase.  S u bjects w h o ha ve a “ D o N ot Use” o utc o me or a n “ As k a 
D oct or” o utc o me a n d d o n ot c o nfir m wit hi n t he We b  A p p t hat t he y s p o ke t o a d oct or will n ot 
be pe r mitte d i nt o t he h o me use p hase of t he st u d y. 
 
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After t he  e nr oll me nt visit, t he partici pa nt will e nter a 6- m o nt h use peri o d w here t he y will re- 
p urc hase st u d y dr u g a vaila ble o nl y t hr o u g h a n o nli ne p urc hase via t he We b  A p p. Partici pa nts 
will be re q uire d t o  c o m plete a  T A S S  re or der assess me nt t o c o nfir m  t he y are still “ O K t o Use” 
pri or t o  re-p urc hase. Partici pa nts will be i nstr ucte d  t o use a n e Diar y t o rec or d w he n t he y t o o k 
st u d y dr u g, ha ve c ha n ges t o a n y me dicati o ns a n d ha ve a n y c ha n ges i n healt h stat us. T he 
C M O G  cli nicia n will  perf or m a tele p h o ne stat us c hec k wit h  partici pa nts  at 6 0 a n d 1 2 0 da ys t o 
assess a n y c ha n ges i n healt h a n d/ or me dicati o ns as well as a n y a d diti o nal  st u d y-relate d iss ues 
( n o i nstr ucti o n will be pr o vi de d re gar di n g t he use of t he pr o d uct). Virt ual Visit 2 will be 
c o m plete d acc or di n g t o t he pr oce d ures descri be d i n t he Sc he d ule of Acti vities ( S o A), Secti o n 
1. 3  a n d details pr o vi de d i n  Secti o n 8  of t he pr ot oc ol.  A 3 0- da y f oll o w- u p p h o ne call will be 
perf or me d after st u d y dr u g c o m pleti o n/ disc o nti n uati o n t o assess partici pa nts stat us wit h 
re gar d t o A Es. 
4. 2  
Scie ntific  R ati o n ale  f or St u d y  Desi g n 
Heart  disease  is t he lea di n g ca use of deat h  f or b ot h me n  a n d w o me n  i n t he U nite d  States  a n d 
w orl d wi de (Merca d o et al 2 0 1 5 ). Ele vate d c h olester ol is a ke y ris k fact or f or heart disease, 
a n d w hile l o weri n g c h olester ol wit h stati n dr u gs re d uces car di o vasc ular m or bi dit y a n d 
m ortalit y, o nl y a b o ut half of t he pe o ple i n t he U nite d States w h o re q uire t hera p y are c urre ntl y 
bei n g treate d (Merca d o et al 2 0 1 5 ). T his re prese nts a s u bsta ntial p u blic healt h iss ue f or t he 
U nite d Stat es. T here are n u mer o us  reas o ns w h y pe o ple are n ot treate d, b ut w hat is clear is t hat 
easier access t o safe, effecti ve, a n d aff or da ble t hera p y w o ul d ha ve a si g nifica nt p ositi ve 
i m pact o n p u blic healt h.  O ne wa y t o si m plif y access t o stati n t hera p y w o ul d be to ma ke it 
a vaila ble t o c o ns u mers wit h o ut a prescri pti o n (e. g., O T C).  Past atte m pts t o ac hie ve a n O T C 
s witc h f or stati n treat me nt ha ve faile d d ue t o c o ncer ns a b o ut t he efficac y of t he stati ns t hat 
were teste d, a n d beca use   c o ns u mers were  u na ble t o pr o perl y self-select. T he  Crest or  O T C  
pr o gra m a d dresses t hese t w o c o ncer ns b y usi n g Crest or 5 m g (a safe a n d hi g hl y effecti ve d ose 
of r os u vastati n wit h mi ni mal i nteracti o ns) a n d a T A S S t o ol t hat e ns ures t he me dici ne is o nl y 
ma de a vaila ble t o c o ns u mers f or w h o m it is a p pr o priate  (Astra Ze neca P har mace uticals L P 
2 0 2 1 ). C o m plete d st u dies e val uati n g D F L c o m pre he nsi o n, CI L c o m pre he nsi o n, We b A p p 
c o m pre he nsi o n, H u ma n Fact ors, Tar gete d Self -Selecti o n a n d All -c o mers Self - Selecti o n ha ve 
s h o w n t hat t his a p pr oac h is  via ble. Base d o n t he s uccess of t hese n o n -i nter ve nti o nal 
be ha vi oral st u dies, Astra Ze neca is rea d y t o pr ocee d wit h t he A U S. 
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T he A U S is desi g ne d t o test t he a bilit y of partici pa nts t o i n p ut t heir me dical data i nt o a We b 
A p p i n or der t o get a c orrect T A S S o utc o me f or t he i nitial p urc hase as well as t o assess t heir 
a bilit y t o c orrectl y e nter t heir o n g oi n g healt h stat us i nt o t he We b A p p t o de m o nstrate pr o per 
use of n o n prescri pti o n r osu vastati n  d uri n g t he use  peri o d.  N o n prescri pti o n r os u vastati n will 
o nl y be a vaila ble o nli ne f or p urc hase via t he We b A p p a n d direct s hi p me nt t o t he partici pa nt. 
It is i nte n de d f or use b y: 
•  
Males  2 0- 3 9 years  of a ge  wit h  hi g h L D L - C ( 1 6 0- 1 8 9 m g/ d L) pl us  fa mil y hist or y  of 
car di o vasc ular disease ( C V D) ( m ot her/sister y o u n ger t ha n 6 5 years of a ge or 
fat her/ br ot her y o u n ger t ha n 5 5 years of a ge) 
•  
Fe males  5 0- 7 5 years  of a ge wit h  A S C V D  ris k sc ore bet wee n  7. 5 % - < 2 0 %  a n d L D L -C 
7 0- 1 8 9 m g/ d L 
•  
Males  4 0- 7 5 years  of a ge wit h  A S C V D  ris k sc ore bet wee n  7. 5 % - < 2 0 % a n d L D L -C 
7 0 _ 1 8 9 m g/ d L 
•  
Fe males  5 0- 7 5 years  of a ge wit h  A S C V D  ris k sc ore bet wee n  5 % - < 7. 5 % pl us o ne ris k 
e n ha nci n g fact or a n d L D L -C 7 0 - 1 8 9 m g/ d L 
•  
Males  4 0- 7 5 years  of a ge wit h  A S C V D  ris k sc ore bet wee n  5 % - < 7. 5 % pl us  o ne ris k  
e n ha nci n g fact or a n d L D L -C 7 0 - 1 8 9 m g/ d L 
•  
Dia betics  (fe males 5 0- 6 0 or males  4 0- 5 0 years  of a ge) wit h  L D L - C bet wee n  7 0- 1 8 9 
m g/ d L a n d wit h A S C V D ris k bel o w 2 0 % 
 
W he n  o n t he mar ket, c o ns u mers  will  access t he We b  A p p  t hr o u g h a n y de vice t hat has  i nter net 
access. O nce t he y access t he site, t he y will ha ve t o a ns wer a series of q uesti o ns i n or der t o 
q ualif y f or treat me nt.   If t he y q ualif y, t he y will e nter a n e C o m merce e n vir o n me nt w here t he y 
will create a pers o nal acc o u nt a n d e nter s hi p pi n g a n d p urc hasi n g i nf or mati o n. If t he y or der 
dr u g, it will be s hi p pe d t o t he m.  C o ns u mers will  be a ble t o p urc hase a li mite d s u p pl y (e. g., 
4 5 or 9 0 da ys).  Wit hi n  a pre-s pecifie d wi n d o w bef ore  t heir s u p pl y r u ns o ut, t he c o ns u mer will  
be a ble t o or der a d diti o nal dr u g t hr o u g h t he We b A p p. H o we ver, bef ore t he y ca n re or der, t he 
We b A p p will as k t he m a li mite d n u m ber of healt h -relate d me dical q uesti o ns t o e ns ure t hat 
t he y are still eli gi ble f or treat me nt. C o ns u mers will als o be as ke d t o retest t heir c h olest er ol 
a n d e nter t heir L D L - C i nt o t he a p p t o e ns ure t he y are getti n g a n a de q uate treat me nt effect.  
Tra nsacti o nal e mails will be se nt t o let t he m k n o w  t he stat us of t heir dr u g or ders, t o re mi n d 
t he m t o retest a n d t o ta ke t heir me dicati o n  dail y. All  c ust o mers  recei ve tra nsacti o nal e mails, 
w hic h is a sta n dar d practice i n  a n e C o m merce e n vir o n me nt.  I n-mar ket, c ust o mers ma y als o 
“ o pt-i n” t o recei ve a d diti o nal re mi n ders or healt h-relate d i nf or mati o n. 
T o test o ur e C o m merce a p pr oac h a n d e ns ure t hat o ur a p pr oac h hel ps t o e ns ure t he pr o per use 
of n o n prescri pti o n r os u vastati n, t he A U S will mi mic, as m uc h as p ossi ble i n a cli nical trial, t he 
i n-mar ket setti n g.  S u bjects will see a d vertise me nts f or partici pati o n i n a st u d y f or a ne w 

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O T C/ n o n prescri pti o n me dici n e. If t he y are i ntereste d, t he y c o ntact a Call Ce nter f or pre- 
scree ni n g a n d, if t he y q ualif y, recei ve a li n k t o t he We b  A p p. S u bjects will ta ke t he i nitial 
T A S S assess me nt.  If t he y recei ve a n “ O K t o Use” o utc o me, t he y will be as ke d t o c o ntact t he 
Call Ce n ter t o set u p a virt ual visit t o re vie w t heir me dical a n d me dicati o n hist or y a n d 
la b orat or y a n d B P data. S u bjects w h o recei ve a n “ As k a D oct or” o utc o me ma y als o be 
eli gi ble pr o vi de d t he y c o ntact t heir d oct or, reta ke t he i nitial  T A S S assess me nt a n d c o nfir m a 
d oct or sai d it is O K t o ta ke Crest or O T C.   Pr o vi de d t he partici pa nt d oes n ot ha ve a si g nifica nt 
c o ntrai n dicati o n t o treat me nt (e. g., we lear n t hat t he partici pa nt is pre g na nt d uri n g Virt ual 
Visit 1), t he y will be a ble t o or der a 4 5 - or 9 0- da y dr u g s u p pl y.  All s u bse q ue nt re or ders are 
perf or me d  usi n g  t he We b  A p p, w hic h  re q uires t he m t o c o nfir m  t hat t he y ha ve ha d n o 
si g nifica nt c ha n ges t o t heir me dical a n d me dicati o n hist or y. T he y will als o be as ke d t o retest 
t heir L D L-C a n d e nter it i nt o t he We b  A p p. Pr o vi de d t he partici pa nt meets t he D F L criteria 
pr o gra m me d i nt o t he We b  A p p f or c o nti n ue d use, t he y ca n re or der me dicati o n. 
Beca use partici pa nts i n t he  A U S will p urc hase n o n prescri pti o n r os u vastati n calci u m o nli ne, 
t he y will  recei ve e C o m merce  tra nsacti o nal c o m m u nicati o ns (e mails) t hat o ne w o ul d e x pect t o 
recei ve w he n  ma ki n g a n o nli ne p urc hase. Tra nsacti o nal  e mails will  be se nt t o partici pa nts 
d uri n g t he trial t o let t he m k n o w t he stat us of t heir or ders, t heir eli gi bilit y t o re or der, a n d t o 
re mi n d t he m t o retest. S o me tra nsacti o nal messa ges will be acc o m pa nie d b y sec o n dar y 
messa ges rei nf orci n g D F L  re q uire me nts (e. g., a d here nce re mi n ders). T here will be n o “ o pt-i n” 
o pti o ns i nc or p orate d i nt o t his st u d y. All partici pa nts i n t he  A U S will ha ve a si milar 
e C o m merce e x perie nce t hat will mi mic, as m uc h as p ossi ble, t he i n -mar ket setti n g.  
 
 
4. 3  
J ustific ati o n  f or D ose  
T he 5 m g d ose of r os u vastati n was c h ose n f or n o n prescri pti o n use beca use it has a safet y 
pr ofile c o m para ble t o place b o a n d is hi g hl y efficaci o us, l o weri n g L D L- C bet we e n 4 0 % t o 
5 0 % i n c o ntr olle d cli nical trials.   T he d ose pla n ne d f or t his st u d y is base d off t he i nte n de d 
d ose f or t he O T C  pr o d uct 
 
 
4. 4  
E n d  of  St u d y  Defi niti o n  
A partici pa nt  is c o nsi dere d t o ha ve c o m plete d t he st u d y if he/s he has c o m plete d all p hases  of 
t he st u d y i ncl u di n g Virt ual Visit 2. Partici pa nts w h o disc o nti n ue wit h s ufficie nt me dical a n d 
me dicati o n hist or y i nf or mati o n a n d, w he n necessar y, a verifie d L D L- C c ollecte d pri or t o 
st o p pi n g t he st u d y t o deter mi ne a fi nal use o utc o me a n d has n ot wit h dra w n fr o m t he st u d y are 
als o c o nsi dere d t o ha ve c o m plete d t he st u d y. 
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A 3 0- da y f oll o w- u p p h o ne call will  be perf or me d  after st u d y dr u g c o m pleti o n/ disc o nti n uati o n 
t o assess partici pa nts stat us wit h re gar d t o A Es. T he st u d y will e n d w he n t he last p h o ne call is 
c o m plete d. 
5  
S T U D Y  P O P U L A TI O N  
T he st u d y p o p ulati o n will  i ncl u de t he f oll o wi n g: 
Descri pti o n  
#  of  P artici p a nts  
All -c o mers p o p ulati o n a ges 2 0 *-7 5 w h o self - 
re p ort ha vi n g c o ncer n  a b o ut hi g h c h olester ol or 
heart healt h  
E nr olle d:  1, 2 2 0  
E val ua ble * *: At least 5 0 0 wit h a  
g oal of 1 0 0 of li mite d literac y 
* Fe males 2 0 -4 9  will be  recr uite d u ntil fift y  fe males u n der t he a ge of 5 0  years c o m plete t he i nitial T A S S 
assess me nt i n t he We b A p p.  After t his q u ota  of fift y  fe males u n der  t he a ge of 5 0  years  ol d  is met,  t he i ncl usi o n 
criterio n  will be  re vise d t o fe males 5 0-7 5 years ol d.  
* * E val ua ble  mea ns  t he partici pa nt c o m plete d  Virt ual Visit 2  or  has  s ufficie nt me dical a n d  me dicati o n  hist or y  
i nf or mati o n a n d, w he n necessar y, a verifie d L D L-C c ollecte d pri or t o st o p pi n g t he st u d y t o deter mi ne a fi nal use 
o utc o me.  
 
Pr os pecti ve a p pr o val of pr ot oc ol de viati o ns t o recr uit me nt a n d e nr oll me nt criteria, als o k n o w n 
as pr ot oc ol wai vers or e xe m pti o ns, is n ot per mitte d. 
5. 1  
Recr uit me nt  Str ate g y  
A n  a p pr o priate recr uit me nt strate g y is critical f or a n y st u d y t o s uccessf ull y c o m plete wit h  t he 
ri g ht partici pa nt p o p ulati o n. As  tec h n ol o g y a n d di gital c o n necte d ness  ha ve i ncrease d o ver t he 
years, m ost c o ns u mers ha ve de vel o pe d a “ di gital f o ot pri nt.” T his refers t o t he i nf or mati o n 
a b o ut a partic ular pers o n t hat e xists o n t he i nter net  as a res ult of t heir o nli ne acti vit y. T he 
p ote ntial t o le vera ge t his i nf or mati o n f or di gital recr uit me nt has gr o w n. 
D uri n g t he All -c o mers Self -Selecti o n  st u d y, t he maj orit y of partici pa nts met a “ D o N ot Use” 
criteri o n a n d were st o p pe d fr o m pr ocee di n g b y t he T A S S. O nl y ~ 5 % of t he partici pa nts t hat 
c o m plete d  t he All -C o mers  S S  st u d y o btai ne d a n “ O k t o Use”  o utc o me. T his  was  e x pecte d as 
t he g oal of t his sta n d-al o ne Self -Selecti o n st u d y was t o de m o nstrate t hat partici pa nts c orrectl y 
i de ntifie d if t he y ha d a “ D o N ot Use” c o n diti o n a n d t hat T A S S c orrectl y st o p pe d t hem fr o m 
pr ocee di n g. 
I n t he A U S, a n all -c o mers p o p ulati o n will als o be recr uite d; h o we ver, o nl y  t h ose w h o o btai n 
T A S S  o utc o mes of “ O K t o Use”  or “ As k a D oct or” a n d i n dicate t he d oct or ga ve t he m 
per missi o n t o use n o n prescri pti o n r os u vastati n will be a ble t o pr ocee d  t o a p urc hase a n d use 
t he pr o d uct i n a n u ns u per vise d O T C  e n vir o n me nt. Base d  o n t he recr uit me nt metrics  fr o m t he 
All - C o mers S S st u d y, it is e x pecte d t hat a p pr o xi matel y 8 0, 0 0 0 c o ns u mers will nee d t o  
res p o n d t o o ur a d vertisi n g a n d c o ntact t he Call Center f or pre -scree ni n g i nt o t he A U S.  As 
s uc h, we i nte n d t o use t he a d va nta ges t hat di gital recr uiti n g aff or ds us t o m ore efficie ntl y 

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e nr oll t he A U S. T his will all o w us t o c o m plete t he st u d y wit h s ufficie nt partici pa nts t o 
c o m plete a r o b ust statistical a nal ysis. 
B y usi n g a c o ns u mer’s “ di gital f o ot pri nt,” a d vertisi n g ca n be tar gete d m ore efficie ntl y b y 
k n o wi n g ke y pieces  of i nf or mati o n  a b o ut a s u bject wit h o ut directl y  as ki n g f or t he i nf or mati o n. 
I nf or mati o n s uc h as a ge, ge n der, car diac e ve nt hist or y, or stati n use ca n be utilize d t o prese nt 
t he a d vertise me nts s pecificall y t o t h ose s u bjects. Le vera gi n g t his strate gic a p pr oac h i n 
c o nj u ncti o n wit h tra diti o nal a d vertisi n g will all o w us t o narr o w t he t o p of t he recr uit me nt 
f u n nel. At t he sa me ti me, we ca n e ns ure we ha ve n ot biase d or i nfl ue nce d t he s u bject b y 
as ki n g q uesti o ns t hat mi g ht i m pact h o w t he y w o ul d c o m plete t he assess me nt i n t he We b A p p 
or h o w t he y w o ul d res p o n d t o t he pre-scree ni n g pr ocess  wit h  t he Call  Ce nter. It  is i m p orta nt t o 
n ote t hat we are a d vertisi n g a n d tar geti n g i n a ma n ner c o nsiste nt wit h h o w we will a d vertise 
a n d tar get i n di vi d uals i n t he real w orl d w he n t he pr o d uct is la u nc he d. 
T heref ore, s o me of t he tactics use d i n t he recr uit me nt lear ni n gs fr o m t he Self -Selecti o n  st u d y 
will c o nti n ue t o be le vera ge d, s uc h as di gital a d vertisi n g met h o ds t hat i ncl u de pai d searc h, 
s ocial me dia, a n d dis pla y a d vertisi n g, tra diti o nal recr uit me nt met h o ds (e. g., ra di o, T V, pri nt, 
c o m m u nit y  o utreac h) a n d s u p ple me ntal met h o ds (e. g., a g gre gati o n t hr o u g h e xisti n g net w or ks 
a n d data bases). H o we ver, we will als o be tar geti n g  base d o n a d diti o nal ke y i nf or mati o n s uc h 
as a ge, ge n der, car diac e ve nts, a n d stati n use w hic h, as  state d a b o ve, are si milar met h o ds t hat 
will be use d w he n t he pr o d uct is c o m mercialize d.  
Met h o ds of  recr uit me nt ma y  als o i ncl u de t he f oll o wi n g, w hic h  ca n be use d  al o ne or, i n 
c o m bi nati o n: 
Di git al  
Tr a diti o n al  
S u p ple me nt al  
Ke y w or d  Searc hes,  A ge,  Ge n der,  
T o pics/I nterests,  A u die nce base d, 
Ge o gra p hicall y base d, O nli ne Be ha vi or, 
Retar geti n g (s h o wi n g a ds a gai n i n t he 
f ut ure if a c o ns u mer s h o we d i nterest i n t he 
st u d y b ut di d n ot call t he Call Ce nter). 
Ge o gra p hicall y  base d, S pecific  
C ha n nels, S pecific 
Ne ws pa pers/ Ma gazi nes, S peci fic 
Ra di o Stati o ns  
A ge,  Ge n der,  C o n diti o ns, 
Ge o gra p hicall y  base d  
 
5. 2  
I ncl usi o n Criteri a  
Partici pa nts  are eli gi ble t o be i ncl u de d i n t he st u d y o nl y if all of t he f oll o wi n g criteria a p pl y: 
1  
Males, 2 0 -7 5  years  of a ge. 
2  
Fe males, 2 0 - 7 5 years of a ge  ( T his i ncl usi o n criteri o n will be a p plie d u ntil 5 0 fe males 
u n der t he a ge of 5 0 years c o m plete t he i nitial T A S S assess me nt i n t he We b A p p.  After  
t his q u ota of 5 0 w o me n u n der t he a ge of 5 0 years  ol d is met, t he i ncl usi o n criteri o n will  be 
re vise d t o w o me n 5 0-7 5 years ol d).  

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3  
Res p o n d t o a d vertisi n g re gar di n g a c o ncer n a b o ut hi g h c h olester ol or heart  healt h.  
4  
A ble  t o rea d s pea k a n d u n dersta n d E n glis h.  
 
A d diti o nal Criteria  f or I ncl usi o n i nt o Act ual  Use  (at Virt ual  Visit  1)  
1  
Partici pa nt  rea ds a n d si g ns t he I nf or me d C o nse nt f or m. 
 
5. 3  
E xcl usi o n  Criteri a  
Partici pa nts  are e xcl u de d fr o m t he st u d y if a n y of t he  f oll o wi n g criteria a p pl y:  
E xcl usi o n Criteria  
1  
T he  partici pa nt  or a n y o ne i n t heir h o use h ol d is c urre ntl y e m pl o ye d b y a n y of t he 
f oll o wi n g: 
− 
A p har mac y  or p har mace utical c o m pa n y 
− 
A c o ns u mer healt hcare  c o m pa n y 
− 
A ma n ufact urer  of  me dici nes  
− 
A ma na ge d care  or healt h i ns ura nce c o m pa n y 
− 
A healt hcare practice  
− 
A n  e m pl o yee of Astra Ze neca  or C o nce ntrics Researc h  
2  
T he  partici pa nt  has e ver bee n  trai ne d or e m pl o ye d as a healt hcare  pr ofessi o nal ( p h ysicia n, 
n urse, n urse practiti o ner, p h ysicia n assista nt, p har macist). 
3  
T he  partici pa nt  has,  or ca n n ot recall w het her he/s he  has,  recei ve d a n i n vesti gati o nal 
t hera p y as part of a cli nical trial i n t he pre vi o us t wel ve ( 1 2) m o nt hs. 
4  
T he  partici pa nt  is n ot willi n g  t o pr o vi de  c o ntact i nf or mati o n. 
5  
Pre vi o us e nr oll me nt i n t he prese nt st u d y. 
6  
T he  partici pa nt  has a maili n g  a d dress i n Alas ka, or t heir maili n g  a d dress  is a P ost Office 
( P O) B o x. 
7  
T he  partici pa nt  is n ot willi n g  t o c o m plete a n  e Diar y. 
8  
T he partici pa nt is a w o ma n of c hil d beari n g p ote ntial a n d is n ot f oll o wi n g c o ntrace pti o n 
g ui deli nes or is  n ot  willi n g  t o f oll o w c o ntrace pti o n g ui deli nes i ncl u di n g practici n g 
a bsti ne nce or usi n g at least 1 of t he f oll o wi n g acce pta ble met h o ds of birt h c o ntr ol f or at 
least 1 m o nt h pri or t o e ntr y i nt o t he st u d y a n d f or 1 m o nt h after st u d y c o m pleti o n: 
h or m o nal – oral, i m pla nta ble, i njecta ble, or tra ns der mal; mec ha nical – s per mici de i n 
c o nj u ncti o n wit h  a barrier s uc h as a  c o n d o m or dia p hra g m; intra uteri ne de vice; or s ur gical 
sterilizati o n of part ner. 
9  
T he  partici pa nt  d oes n ot ha ve access  t o t he i nter net. 

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1 0  T he  partici pa nt  d oes n ot ha ve a n  e mail a d dress  or  t he a bilit y t o recei ve e mails. 
1 1  T he partici pa nt res p o n ds t o t he Si n gle Ite m Literac y Scree ner 2 ( SI L S 2) q uesti o n  (C he w 
et al 2 0 0 8) “ H o w c o nfi de nt are y o u filli n g o ut me dical f or ms b y y o urself?” wit h eit her 
‘e xtre mel y’ or ‘ q uite a bit.’ (If t he q u ota f or n or mal literac y is met, b ut t he li mite d literac y 
tar get is n ot met, t he SI L S 2 e xcl usi o n will be use d t o hel p i ncrease t he perce nta ge of 
li mite d literac y partici pa nts  at Virt ual  Visit  1. Partici pa nts  i de ntifie d as n or mal literac y b y 
Ra pi d Esti mate of A d ult Literac y i n Me dici ne ( R E A L M) testi n g at Virt ual Visit  1 will  n ot 
be e xcl u de d fr o m e ntr y i nt o t he treat me nt p hase of t he st u d y.) 
1 2  I na bilit y t o c o n d uct i nter vie ws i n a pri vate l ocati o n s o t hat se nsiti ve i nf or mati o n a b o ut t he 
partici pa n t or st u d y w o ul d n ot be o ver hear d b y ot hers n ot per mitte d t o hear s uc h 
i nf or mati o n. 
A d di ti o nal Criteria  f or E xcl usi o n fr o m Act ual  Use  (at Virt ual  Visit  1) C o nfir mati o n b y C M O G 
cli nicia n: 
1  
T hat  t he partici pa nt  is pre g na nt, as deter mi ne d  b y  a n a p pr o ve d self-a d mi nistere d  O T C 
uri ne pre g na nc y test c o n d ucte d f or all fe male partici pa nts of c hil d beari n g p ote ntial 
( Fe male partici pa nts w h o are n ot p ost- me n o pa usal or s ur gicall y sterile). 
2  
T hat  t he partici pa nt  is breast fee di n g. 
3  
T hat t he partici pa nt  has a n aller g y t o r os u vastati n. 
5. 4  
Lifest yle  C o nsi der ati o ns  
N o  lifest yle restricti o ns are re q uire d f or t his st u d y. 
5. 5  
Pre -Scree n  F ail ures  
Pre -scree n fail ures are defi ne d as  all s u bjects w h o  meet o ne of t he f oll o wi n g cate g ories: 
•
Di d  n ot meet  S S i ncl usi o n  or met  S S e xcl usi o n
•
Q ualifie d ref use d
•
Recei ve d  We b  A p p  li n k b ut di d n ot c o m plete t he T A S S  assess me nt.
•
Recei ve d  We b  A p p  li n k a n d recei ve d a “ D o N ot  Use”  o utc o me.
•
Recei ve d  We b  A p p  li n k a n d recei ve d a n “ As k a D oct or” o utc o me a n d di d n ot g o bac k  i nt o
t he We b A p p a n d i n dicate a d oct or sai d it was o ka y t o pr ocee d.
•
Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  o utc o me or a n  “ As k a D oct or” o utc o me
a n d i n dicate d a d oct or sai d it was o ka y t o pr ocee d b ut ne ver create d a We b A p p acc o u nt.
•
Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  o utc o me or a n  “ As k a D oct or” o utc o me
a n d i n dicate d a d oct or sai d it was o ka y t o pr ocee d, create d a We b A p p acc o u nt b ut di d n ot
ma ke a n i nitial p urc hase of st u d y dr u g.

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•  
Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  o utc o me or  a n “ As k a D oct or” o utc o me 
a n d i n dicate d a d oct or sai d it was o ka y t o pr ocee d, create d a We b A p p acc o u nt, ma de a n 
i nitial p urc hase of st u d y dr u g b ut di d n ot sc he d ule t heir first visit. 
•  
Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  o utc o me or  a n “ As k a D oct or” o utc o me 
a n d i n dicate d a d oct or sai d it was o ka y t o pr ocee d, sc he d ule d t heir first visit b ut di d n ot 
si g n I C F (eit her di d n ot s h o w f or t heir first visit or s h o we d b ut deci de d n ot t o si g n I C F). 
 
I nf or mati o n o n pre-scree n fail ures will be re p orte d. A mi ni mal set of pre -scree n fail ure 
i nf or mati o n is re q uire d t o e ns ure tra ns pare nt re p orti n g of pre-scree n fail ure s u bjects t o meet 
t he C o ns oli date d Sta n dar ds of Re p orti n g Trials  ( C O N S O R T) p u blis hi n g re q uire me nts a n d t o 
res p o n d t o q ueries fr o m re g ulat or y a ut horities. Mi ni mal i nf or mati o n i ncl u des de m o gra p h y, 
pre- scree n fail ure details, a n d eli gi bilit y criteria (Sc h ulz et al 2 0 1 0 ).  
I n di vi d uals w h o  d o n ot meet  t he criteria f or partici pati o n i n t his st u d y ( pre-scree n fail ures) 
ma y n ot be rescree ne d.  
6  
S T U D Y  I N T E R V E N TI O N 
St u d y i nter ve nti o n is defi ne d as a n y i n vesti gati o nal i nter ve nti o n(s), mar kete d pr o d uct(s), 
place b o, or me dical de vice(s)  i nte n de d t o be a d mi nistere d t o  a st u d y partici pa nt acc or di n g t o 
t he st u d y pr ot oc ol. 
6. 1  
St u d y  I nter ve nti o n A d mi nistere d  
6. 1. 1  
I n vesti g ati o n al Pr o d ucts  
T a ble  2 
I n vesti g ati o n al Pr o d ucts  
A R M  N a me  
Crest or  5 m g  
I nter ve nti o n N a me  
R os u vastati n  calci u m 
T y pe  
C o m bi nati o n  pr o d uct  ( Dr u g a n d Sa M D)  
D ose F or m ul ati o n  
Ta blet  
U nit D ose Stre n gt h(s)  
5 m g  
D os a ge  Le vel(s)  
1  ta blet o nce-dail y  
R o ute of 
A d mi nistr ati o n  
Oral  
Use  
L o wer  C h olester ol,  a ke y  ris k fact or f or heart disease.  
I M P a n d  NI M P  
I M P 

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S o urci n g  
Dr u g  pr o vi de d  ce ntrall y b y  t he S p o ns or  t hr o u g h Astra Ze neca  i P R 
P har mace uticals I nc. ma n ufact uri n g site  
S oft ware  pr o vi de d  b y  Astra Ze neca  t hr o u g h I dea E v ol ver  
P ac k a gi n g  a n d 
L a belli n g  
St u d y  I nter ve nti o n will be  pr o vi de d  i n 1 or  2 4 5 -c o u nt b ottles.  Eac h b ottle  
will be la belle d as per C F R re g ulati o ns.  
 
6. 1. 2  
S oft w are  as  a C o nstit ue nt  P art  
T he  pr o p ose d We b  A p p  is bei n g de vel o pe d as a c o nstit ue nt part  of a c o m bi nati o n pr o d uct b y a 
t hir d-part y c olla b orati n g cl osel y wit h Astra Ze neca.  
T he We b A p p feat ures a T A S S t o ol w hic h all o ws c o ns u mers t o a ns wer a select set of healt h -
relate d q uesti o ns i n or der t o deter mi ne c o ns u mer s uita bilit y f or self-selecti o n, p urc hasi n g, a n d 
o n g oi n g a d mi nistrati o n a n d a d here nce  of Crest or O T C  (i n vesti gati o nal pr o d uct). Crest or O T C  
will o nl y be a vaila ble o nli ne f or p urc hase via t he We b A p p a n d direct s hi p me nt t o t he 
c o ns u mer. T he T A S S t o ol is a s pecific a n d critical “f u ncti o n” of t he br oa der We b A p p.  T he 
T A S S t o ol s pecificall y utilizes a n al g orit h m (i.e., decisi o n tree a n d b usi ness  l o gic ali g ne d t o 
t he D F L a n d treat me nt g ui deli nes)  t hat o perates o n c o ns u mer data i n p ut t o pr o d uce a n 
o utc o me re gar di n g t he a p pr o priate ness of Crest or O T C treat me nt f or t he res pecti ve c o ns u mer.  
T he br oa der We b A p p als o i ncl u des a d diti o nal c o m p o ne nts s uc h as a we lc o me state me nt, 
pri vac y state me nt, acc o u nt set u p, s h o p pi n g cart c hec k o ut, a n d acc o u nt ma na ge me nt, w hic h are 
n ot c o nsi dere d me dical de vice f u ncti o ns.  
T he T A S S acts  as a di gitize d, i nteracti ve  versi o n of t he D F L, all o wi n g c o ns u mers t o a ns wer a 
d y na mic a n d p ers o nalize d  set of healt h -relate d q uesti o ns, i n lie u of br o wsi n g/searc hi n g a D F L 
f or i nf or mati o n perti ne nt t o t he m. It als o calc ulates a 1 0- year A S C V D ris k base d o n t he 
P o ole d C o h ort E q uati o n ( P C E) t o deter mi ne c o ns u mer s uita bilit y f or m o derate -i nte nsit y stati n 
treat me nt i n acc or da nce wit h t he 2 0 1 8 Treat me nt G ui deli ne (Gr u n d y et al 2 0 1 8 ). P ote ntial 
c o ns u mers are eli gi ble t o p urc hase Crest or O T C if t he y meet t he re q uire me nts f or safe use 
acc or di n g t o t he D F L a n d ha ve a n a p pr o priate calc ulate d A S C V D ris k sc ore.  
6. 2  
Pre p ar ati o n/ H a n dli n g/ St or a ge/ Acc o u nt a bilit y  of  I nter ve nti o ns 
1  
A detaile d pr ocess fl o w c hart f or pr o d uct acc o u nta bilit y has bee n de vel o pe d (see 
A p pe n di x C ). T he st u d y pr o d uct will be st ore d at a Ce ntral De p ot t o pre pare t he pr o d uct 
a n d acc o m pa n yi n g d oc u me ntati o n ( D F L, CI L, i n v oice/ pac ki n g sli p) f or s hi p me nt via a 
deli ver y ser vice.  T he st u d y pr o d uct will be st ore d i n a sec ure a n d m o nit ore d area i n 
acc or da nce wit h t he  la belle d st ora ge c o n diti o ns wit h li mite d access t o o nl y a ut h orize d 
staff. T he C o ntract Researc h Or ga nizati o n ( C R O)  will w or k wit h t he Ce ntral De p ot t o 
e ns ure o nl y e nr olle d a n d i n vesti gat or -a p pr o ve d partici pa nts will recei ve st u d y pr o d uct f or 
t he i nitial o r d e r.  Pr o vi de d  t he partici pa nt  has  n o  c ha n ges i n healt h  as a d mi nistere d via t he 
We b A p p, s u bse q ue nt re or ders will a ut o maticall y tri g ger s hi p me nt t hr o u g h t he We b A p p 

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t o t he Ce ntral De p ot i m me diatel y u p o n o nli ne p urc hase b y t he partici pa nt. E mails will 
als o be use d t o i nf or m partici pa nts w he n t he y s h o ul d re or der. T he y will recei v e a re or der 
e mail at da y 2 5  f or a 4 5-da y s u p pl y or der a n d at da y  4 5  f or a 9 0- da y s u p pl y or der t h o u g h 
t he We b A p p will all o w t he partici pa nt t o place a n ot her or der after 5 da ys fr o m t he last 
or der deli vere d date f or t he A U S. T his will all o w a n assess me nt  of partici pa nt  be ha vi ors 
ar o u n d re or deri n g of dr u g  d uri n g t he A U S  t o best p ositi o n t he a p pr o priate or deri n g 
wi n d o ws i n- mar ket.  
2  
T he  i n vesti gat or is res p o nsi ble f or fi nal dr u g acc o u nta bilit y, rec o nciliati o n, a n d rec or d 
mai nte na nce (i.e., rec o nciliati o n a n d fi nal dis p ositi o n rec or ds). 
3  
F urt her g ui da nce a n d i nf or mati o n f or t he fi nal dis p ositi o n of u n use d  st u d y i nter ve nti o ns 
are pr o vi de d i n t he Pr o d uct Acc o u nta bilit y L o g . 
 
6. 3  
Me as ures  t o Mi ni mize  Bi as:  R a n d o miz ati o n  a n d  Bli n di n g  
O pe n -la bel, N o bli n di n g at 
site le vel 
T his  is a n o pe n -la bel st u d y; p ote ntial bias will  be re d uce d b y 
ha vi n g partici pa nts use t he me dicati o n  wit h o ut cli nicia n 
s u per visi o n a n d b y kee pi n g t he n u m ber of i nteracti o ns wit h 
st u d y pers o n nel t o a mi ni m u m.  
  
6. 4  
St u d y  I nter ve nti o n C o m pli a nce  
W he n  partici pa nts  ta ke st u d y dr u g at h o me, c o m plia nce wit h  st u d y dr u g will  be assesse d  via a n 
e Diar y, pill c o u nt a n d re or ders. Partici pa nts will be directe d t o s hi p bac k t o C o nce ntrics, t he 
C R O, a n y u n use d pr o d uct as well as pr o d uct i nf or mati o n d uri n g t he fi nal virt ual  site visit. A 
rec or d of t he n u m ber of Crest or 5  m g ta blets dis pe nse d t o a n d ta ke n b y eac h partici pa nt m ust 
be mai ntai ne d a n d rec o ncile d wit h st u d y i nter ve nti o n a n d c o m plia nce rec or ds. O nce pr o d uct is 
recei ve d at C o nce ntrics, a fi nal pill c o u nt will be c o n d ucte d a n d d oc u me nte d o n t he s o urce 
d oc u me nt a n d electr o nic  case re p ort f or m (e C R F).  
T h ose partici pa nts  w h o  ref use t o se n d bac k  t heir pill  b ottles  f or a fi nal pill  c o u nt will  be gi ve n 
t he o pti o n t o c o u nt t he pills wit h t he st u d y pers o n nel via vi de o c o nfere nce at Virt ual Visit 2.  
T his  will  be rec or de d o n s o urce d oc u me ntati o n a n d t he e C R F. 
Dr u g  dis pe nse d  date (i.e., deli ver y  date)  a n d Dr u g  ret ur n date will  als o be rec or de d i n t he Dr u g 
Acc o u nta bilit y f or m.  
6. 5  
C o nc o mit a nt  T her a p y  
A n y  me dicati o n  t hat t he partici pa nt  is recei vi n g at t he ti me of e nr oll me nt  or  recei ves d uri n g 
t he st u d y m ust be rec or de d o n t he C o nc o mita nt Me dicati o n f or m al o n g wit h:  

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•  
Reas o n  f or use  
•  
Dates  of a d mi nistrati o n i ncl u di n g  start a n d e n d dates  
•  
D osa ge i nf or mati o n i ncl u di n g d ose a n d fre q ue nc y 
 
T he  Me dical  M o nit or s h o ul d be c o ntacte d if t here are a n y q uesti o ns re gar di n g c o nc o mita nt or 
pri or t hera p y.  
6. 5. 1  
Resc ue  Me dici ne  
T here is n o  resc ue me dici ne f or t his st u d y. 
6. 6  
D ose  M o dific ati o n  
T here  will  be n o  d ose m o dificati o ns as part  of t his st u d y. 
6. 7  
I nter ve nti o n after  t he E n d  of  t he St u d y  
T here  is n o pla n ne d i nter ve nti o n after t he e n d of t he st u d y. 
7  
DI S C O N TI N U A TI O N  O F  S T U D Y  I N T E R V E N TI O N A N D 
P A R TI CI P A N T DI S C O N TI N U A TI O N/ WI T H D R A W A L  
7. 1  
Disc o nti n u ati o n  of  St u d y  I nter ve nti o n 
A partici pa nt ma y deci de t o per ma ne ntl y disc o nti n ue st u d y me dicati o n f or a n y reas o n at a n y 
ti me or t he C M O G cli nicia n ma y deci de t o per ma ne ntl y disc o nti n ue a partici pa nt fr o m st u d y 
me dicati o n. If st u d y i nter ve nti o n is per ma ne ntl y disc o nti n ue d, t he partici pa nt will be 
sc he d ule d f or a fi nal Virt ual Visit t o c o m plete all Virt ual Visit 2 st u d y pr oce d ures or o btai n 
sufficie nt  me dical  a n d me dicati o n  hist or y  t o deter mi ne  a fi nal use o utc o me if all Virt ual  Visit  2 
assess me nt pr oce d ures ca n n ot be c o m plete d.  See t he S o A  f or data t o be c ollecte d at Virt ual 
Visit 2.  
N ote  t hat disc o nti n uati o n fr o m st u d y i nter ve nti o n is N O T  t he sa me t hi n g as a wit h dra wal  fr o m 
t he st u d y. 
If a partici pa nt deci des t o per ma ne ntl y disc o nti n ue st u d y me dicati o n a n d t heir last T A S S 
assess me nt was “ O K t o Use” or “ As k a D oct or” a n d i n dicate d t he d oct or ga ve t he m 
per missi o n  t o c o nti nue  treat me nt, t he partici pa nt  will  c o m plete a fi nal T A S S  at Virt ual  Visit  2. 
H o we ver, partici pa nts will n ot be re q uire d t o c o m plete t he st u d y ma n date d L D L- C retest.  
W hile a st u d y partici pa nt ma y deci de t o disc o nti n ue st u d y me dicati o n at a n y ti me, t he o nl y 
e ve nts t hat w o ul d res ult i n st u d y me dical pers o n nel i nstr ucti n g t he partici pa nt t o st o p ta ki n g 
r os u vastati n are “ St o p Use”  criteria ( w hic h t he partici pa nt  has n ot self-i de ntifie d a n d ta ke n t he 
acti o n t o st o p use) as liste d bel o w:  

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•  
Pre g na nc y 
•  
Se vere  a n d u ne x plai ne d m uscle  pai n,  te n der ness, or wea k ness  
•  
S y m pt o ms of  li ver pr o ble ms ( u p per bell y  pai n, dar k  uri ne, yell o wi n g of s ki n or w hites  of 
e yes) 
 
If s uc h a sit uati o n occ urs, t he partici pa nt’s dis p ositi o n will be classifie d as “ Pre g na nc y” f or 
t his “ St o p Use” war ni n g or “ A d verse E ve nt” f or Se vere a n d u ne x plai ne d m uscle pai n, 
te n der ness or wea k ness or s y m pt o ms of li ver pr o ble ms “ St o p Use” war ni n gs. T he partici pa nt 
will  be sc he d ule d f or a Virt ual  Visit  2. All  pr oce d ures will  be perf or me d  e xce pt a fi nal T A S S 
a n d a st u d y ma n date d test f or L D L- C.  
7. 2  
P artici p a nt  Wit h dr a w al  fr o m t he St u d y  
•  
Wit h dra wal  mea ns  a n y o ne w h o  si g ne d t he I C F a n d di d n ot c o m plete t he st u d y (see 
Secti o n  4. 4 ) 
•  
A partici pa nt ma y  wit h dra w fr o m t he st u d y at a n y ti me at his/ her o w n re q uest or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or f or safet y, be ha vi oral, 
c o m plia nce, or a d mi nistrati ve reas o ns (e. g., c o nti n uall y dela yi n g visits or i nteracti o ns, 
ref usi n g t o use t he e Diar y, i nt o xicati o n or u n der t he i nfl ue nce of dr u gs). T his  is e x pecte d 
t o be u nc o m m o n. Fail ure t o c o m pl y wit h t he d osi n g re gi me n i n a n d of itself is n ot a 
reas o n f or bei n g wit h dra w n fr o m t he st u d y. 
− 
If a partici pa nt e x presses a desire t o wit h dra w fr o m t he st u d y, t he C M O G will 
atte m pt t o o btai n as m uc h i nf or mati o n as p ossi ble i ncl u di n g fi nal diar y data, u n use d 
dr u g ret ur ne d, a n d a n y i nf or mati o n o n A Es. Wit h dra wals, b y defi niti o n, will  n ot ha ve  
c o m plete d  Virt ual  Visit  2 a n d will  n ot ha ve s ufficie nt data  t o deter mi ne a fi nal use 
o utc o me. 
− 
Wit h dra wals occ urri n g after si g ni n g t he I C F b ut pri or t o dr u g deli ver y t o t he 
partici pa nt will be desi g nate d as “ S S Wit h dra wal” . Wit h dra wals occ urri n g f oll o wi n g 
dr u g deli ver y t o t he partici pa nt are desi g nate d as a n “ A U S I T T Wit h dra wal”. 
 
If t he partici pa nt wit h dra ws  c o nse nt f or discl os ure of f ut ure  i nf or mati o n, t he s p o ns or ma y 
retai n a n d c o nti n ue t o use a n y data c ollecte d bef ore s uc h a wit h dra wal of c o nse nt.  
Detaile d  reas o ns f or wit h dra wal will  be d oc u me nte d i ncl u di n g partici pa nt  ver bati ms.  
7. 3  
L ost  t o F oll o w -u p  
A partici pa nt  will  be c o nsi dere d  l ost t o f oll o w- u p if he or s he  re peate dl y fails t o c o m plete t he 
sc he d ule d virt ual visits a n d is u na ble t o be c o ntacte d b y t he st u d y staff. 
T he  f oll o wi n g acti o ns m ust  be ta ke n  if a partici pa nt fails t o c o m plete a  re q uire d st u d y visit:  

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•  
T here  m ust be a n atte m pt t o c o ntact t he partici pa nt a n d resc he d ule t he misse d  virt ual visit 
as s o o n as p ossi ble a n d c o u nsel t he partici pa nt o n t he i m p orta nce of mai ntai ni n g t he 
assi g ne d visit sc he d ule a n d ascertai n w het her or n ot t he partici pa nt wis hes t o a n d/ or 
s h o ul d c o nti n ue i n t he st u d y. 
•  
Bef ore a partici pa nt  is dee me d l ost t o  f oll o w- u p, t he i n vesti gat or or desi g nee m ust ma ke 
e ver y eff ort t o re gai n c o ntact wit h t he partici pa nt ( w here p ossi ble, 3 tele p h o ne calls [ o n 
differe nt da ys a n d at differe nt ti mes] a n d, if necessar y, a certifie d letter se nt t o t he 
partici pa nt’s  last k n o w n maili n g  a d dress).  T h ese c o ntact atte m pts s h o ul d be  d oc u me nte d 
i n t he partici pa nt’s me dical rec or d. 
•  
S h o ul d t he partici pa nt  c o nti n ue t o be u nreac ha ble,  he/s he will  be c o nsi dere d l ost t o 
f oll o w-u p.  
 
Site pers o n nel, or a n i n de pe n de nt t hir d- part y, will atte m pt t o c ollect t he vital stat us of t he 
partici pa nt  wit hi n  le gal a n d et hical b o u n daries f or all partici pa nts  e nr olle d. P u blic s o urces ma y 
be searc he d f or vital stat us i nf or mati o n. If vital stat us is deter mi ne d as decease d, t his will be 
d oc u me nte d, a n d t he partici pa nt will n ot be c o nsi dere d l ost t o f oll o w- u p. S p o ns or pers o n nel 
will n ot be i n v ol ve d i n a n y atte m pts t o c ollect vital stat us i nf or mati o n.  
Disc o nti n uati o n of t he st u d y as a w h ole is ha n dle d as part  of A p pe n di x A.  
8  
S T U D Y  A S S E S S M E N T S  A N D  P R O C E D U R E S  
•  
I m me diate safet y c o ncer ns s h o ul d be disc usse d wit h t he s p o ns or i m me diatel y u p o n 
occ urre nce  or a ware ness  t o deter mi ne  if t he partici pa nt  s h o ul d c o nti n ue or disc o nti n ue 
st u d y i nter ve nti o n. 
•  
A d here nce t o t he st u d y desi g n re q uire me nts, i ncl u di n g t h ose s pecifie d i n t he S o A,  is 
esse ntial a n d re q uire d f or st u d y c o n d uct. 
•  
All pre -scree ni n g e val uati o ns m ust be  c o m plete d a n d re vie we d t o c o nfir m t hat p ote ntial 
partici pa nts  meet  all eli gi bilit y criteria. T he  i n vesti gat or will mai ntai n  a scree ni n g l o g t o 
rec or d details  of all partici pa nts  scree ne d a n d t o c o nfir m eli gi bilit y or  rec or d reas o ns f or 
scree ni n g fail ure, as a p plica ble. 
•  
Pr oce d ures c o n d ucte d as part of t he partici pa nt’s  r o uti ne cli nical ma na ge me nt  (e. g., li pi d 
pr ofile) a n d o btai ne d wit hi n 1 2 m o nt hs ( + 3- m o nt h wi n d o w) bef ore si g ni n g of t he I C F 
ma y be utilize d f or scree ni n g or baseli ne p ur p oses pr o vi de d t he pr oce d ures met t he 
pr ot oc ol- s pecifie d criteria a n d were  perf or me d  wit hi n  t he ti me fra me defi ne d  i n t he S o A.  
•  
St u d y pr oce d ures a n d t heir ti mi n g are s u m marize d i n t he S o A a n d descri be d bel o w. 
Pr ot oc ol wai vers  or e xe m pti o ns are n ot all o we d. T he  f oll o wi n g ste ps are i n or der of 
pr oce d ures:  
 

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Pri or t o  Virt u al  Visit  1 
1  
All -c o mers w h o  res p o n d t o di gital  or  tra diti o nal a ds will  clic k o n a n a d vertise me nt  (if 
di gital) or visit t he we b pa ge directl y (if seei n g/ heari n g tra diti o nal a d) t o lear n m ore 
a b o ut t he st u d y.  
2  
S u bjects w h o are i ntereste d will call t he C o nce ntrics Call Ce nter t o g o t hr o u g h pre - 
scree ni n g q uesti o ns t hat are c o m prise d of t he i ncl usi o n a n d e xcl usi o n criteria as well 
as de m o gra p hic i nf or mati o n a n d a pri vac y ac k n o wle d g me nt or s u bjects ca n o pt t o 
c o m plete a n o nli ne pre- scree ner. 
3  
T h ose w h o  meet  pre -scree ni n g criteria will  be se nt t he We b  A p p  li n k via e mail fr o m 
t he Call Ce nter. 
4  
T he s u bject will c o m plete t he i nitial T A S S assess me nt t hr o u g h t he We b A p p.  If a 
s u bject d oes n ot k n o w t heir la b n u m bers pri or t o ta ki n g t he i nitial assess me nt a n d is 
u ns ure as t o w here t o o btai n t heir la bs, t he st u d y staff will pr o vi de t he s u bject wit h 
testi n g o pti o ns u p o n re q uest usi n g t he i nf or mati o n pr o vi de d i n t he We b A p p as a 
g ui de, b ut t he s u bject will c h o ose t heir preferre d o pti o n. If a s u bject wis hes t o g o t o a 
d oct or a n d get  a prescri pti o n  f or a la b test, t hat is acce pta ble.  T he y  ca n als o or der a 
h o me test kit. T he st u d y staff will n ot pr oacti vel y tell t he m w hic h testi n g met h o d t o 
use. If a s u bject re q uests assista nce, t he st u d y staff will hel p t he m l ocate a testi n g site 
(e. g., l ocal p har mac y, i n-st ore cli nic) f or testi n g. H o we ver, t he S p o ns or will n ot or der 
t he tests or pa y f or t heir tests i n or der t o o verc o me s o me of t he nat ural barriers t hat  
w o ul d be e x per ie nce d b y t he c o ns u mer w he n atte m pti n g t o access n o n prescri pti o n 
r os u vastati n i n-mar ket.  
5  
S u bjects w h o recei ve a n “ O K t o Use” o utc o me or “ As k a D oct or” o utc o me (a n d 
c o nfir m t hat t heir d oct or sa ys it is O K f or t he m t o use), will t he n be gi ve n a n 
o p p ort u nit y t o p urc hase a 4 5- da y or 9 0- da y ( partici pa nt’s c h oice)  s u p pl y of t he 
pr o d uct t hr o u g h t he We b A p p.  N o dr u g will be s hi p pe d u ntil t he s u bject c o nse nts a n d 
c o m pletes Virt ual Visit 1.  If t he s u bject deci des n ot t o partici pate or t he partici pa nt is 
dee me d n ot el i gi ble t o partici pate at t he e n d of Virt ual Visit 1, t he pr o d uct p urc hase 
price will be ref u n de d. 
6  
U p o n c o m pleti o n of t he i nitial T A S S assess me nt a n d p urc hase, s u bjects will be 
directe d t o call t he Call Ce nter t o  sc he d ule t heir Virt ual Visit 1.  D uri n g t his call, t he 
Call  Ce nter  staff will  c o nfir m  t hat t he s u bject c o nti n ues t o meet  pre-scree ni n g criteria 
a n d has verifie d dia g n ostic n u m bers ( Tri gl yceri des, T C, H D L- C, L D L -C,  B P 
n u m bers, a n d if a p plica ble a hi g h- se nsiti vit y C-reacti ve pr otei n [ hs-C R P] le vel, 
c or o nar y arter y calci u m [ C A C] sc ore a n d waist circ u mfere nce meas ure me nt).  
o  
S u bjects will nee d a verifie d s o urce  f or t heir la b orat or y val ues f or Virt ual  Visit  1.  
Verifia ble  la bs will  be re q uire d i n or der  t o pr ocee d  t o t he use p hase of t he st u d y 
(e xcl u di n g C A C). 

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o  
“ Verifie d” la b orat or y val ues are t h ose f or w hic h t he s u bject has a p pr o priate 
s o urce d oc u me ntati o n (la b orat or y re p ort, D oct or’s office re p ort, etc.) f or t he 
val ues e ntere d i nt o t he We b  A p p  or are la b orat or y val ues res ulti n g fr o m a st u d y 
ma n date d test.  
o  
Verifie d dia g n ostic n u m bers ca n i ncl u de res ults o btai ne d pri or t o c o m pleti n g t he 
i nitial T A S S assess me nt as l o n g as t he s o urce t y pe is wit hi n 1 2 m o nt hs ( + 3-
m o nt h wi n d o w) a n d has a na me t hat matc hes  t he s u bject’s dri ver’s  lice nse or 
ot her i de nt ificati o n wit h a pict ure I D (e. g., sc h o ol I D, militar y I D, pass p ort, etc). 
o  
F or males  a ges 2 0 t o 3 9, a s o urce verifie d  B P  will  n ot be re q uire d si nce B P d oes 
n ot fact or i nt o t he use assess me nt base d o n c urre nt g ui deli nes.  
o  
Call Ce nter re prese ntati ve will ma n date a la b orat or y test or B P meas ure me nt f or 
Virt ual  Visit  1 if t he s u bjects states t hat t he y d o n ot  ha ve a s o urce d oc u me nt f or 
t he data e ntere d i nt o t he We b A p p. 
o  
C A C i ma gi n g res ults will n ot be verifie d if a s u bject i n p uts t his i nf o r mati o n i nt o 
t he We b A p p a n d d oes n ot ha ve a verifie d s o urce. T his data will be d oc u me nte d  
as “ u n verifie d,” b ut t his w o ul d n ot e xcl u de t he m fr o m pr ocee di n g t o partici pate 
i n t he A U S. N o  st u d y ma n date d testi n g will be re q uire d. I n t his i nsta nce, t he 
s u bject’s T A S S e ntr y will be c o nsi dere d acce pta ble. 
o  
F or st u d y ma n date d tests o nl y, t he Call Ce nter re prese ntati ve will hel p 
c o or di nate or l ocate a testi n g site (e. g., l ocal p har mac y, i n -st ore cli nic) f or testi n g 
f or t he tri gl yceri des, c h olester ol  n u m bers a n d, if a p plica ble, hs-C R P. If a  s u bject 
is u na ble t o get t o o ne of  t he l ocal testi n g sites, t he st u d y staff ca n direct t he m t o 
or der a h o me test kit.   S u bjects will n ot be re q uire d t o pa y f or st u d y ma n date d 
testi n g. 
o  
A verifie d s o urce is als o re q uire d f or B P n u m bers f or Virt ual Visit 1. If t he 
s u bject states t he y d o n ot ha ve verifie d B P n u m bers f or t heir Virt ual Visit 1, t he 
st u d y staff ca n hel p t o l ocate a testi n g site f or B P. If a s u bject is u na ble t o get t o 
o ne of t he l ocal testi n g sites a n d  if t he y ha ve a n F D A a p pr o ve d B P de vice at 
h o me, t he y will  be all o we d t o use t heir de vice.  If t he s u bject ca n n ot get t o a l ocal 
testi n g site a n d d oes n ot ha ve a n F D A a p pr o ve d B P de vice at h o me, a B P 
m o nit or will be s hi p pe d t o t he m. Ge neral i nstr ucti o ns o n tec h ni q ues t o meas ure 
B P will be pr o vi de d. 
7  
A pre -st u d y s hi p me nt will be se nt t o t he s u bjects i n a d va nce of t heir Virt ual Visit 1 a n d 
will  c o ntai n pre g na nc y tests (if fe male), a n e Diar y a n d st u d y i nstr ucti o ns. T hese 
i nstr ucti o ns will be re vie we d wit h t he partici pa nt at t he Virt ual Visit 1.  
8  
S u bjects will  recei ve a call a hea d of t heir sc he d ule d Virt ual  Visit  t o re mi n d t he m of t heir 
a p p oi nt me nt ti me a n d t o ha ve t he verificati o n of t he la b orat or y n u m bers a n d B P t he y 
e ntere d i nt o t he We b A p p wit h t he m.  
 

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At  Virt u al  Visit  1 
9  
T he s u bject will c o n nect t o t he o nli ne vi de o li n k, pr o vi de a n I D c hec k t o t he Ce ntral 
Assess or  w h o  will  als o c o nfir m t hat t he s u bject has  verifia ble  dia g n ostic data,  pri or  t o 
s pea ki n g wit h t he C M O G cli nicia n a n d si g ni n g t he i nf or me d c o nse nt. T he Ce ntral 
Assess or will  c o n d uct t his verificati o n  d ue t o t heir a vaila bilit y at t he a p p oi nt me nt ti me a n d 
access t o t he Virt ual we b meeti n g.  
o  
If t he dia g n ostic data  is n ot verifia ble,  t he Virt ual  Visit 1 will  be resc he d ule d. 
o  
If t he Ce ntral Assess or is a ble t o verif y t he s o urce of t he dia g n ostic data, t he data 
is referre d t o as “ verifie d s o urce.” If t he dia g n ostic val ues are a res ult of st u d y 
ma n date d testi n g, t he data is referre d t o as “ verifie d b y S M T”. B ot h t he “ verifie d  
s o urce” a nd “ verifie d  b y S M T”  la b a n d B P res ults  will  be pr o vi de d t o t he C M O G 
cli nicia n fr o m t he Dia g n ostic Re p ort f or m f or c o m pleti n g t he C M O G cli nicia n 
T A S S.  As n ote d earlier, males 2 0 - 3 9 will n ot be re q uire d t o ha ve a verifie d  
s o urce or S M T f or B P si nce  B P d oes n ot fact or i nt o t he use assess me nt f or t his 
a ge gr o u p base d o n c urre nt g ui deli nes. 
1 0  O nce  t he dia g n ostic data  has bee n  verifie d, t he partici pa nt will  si g n t he I C F, a n d all use 
eli gi bilit y criteria will be c o nfir me d.  
1 1  W o me n  of c hil d beari n g p ote ntial will  ta ke a uri ne  pre g na nc y test a n d s h o w t he test res ults 
t o t he C M O G via t he vi de o. 
o  
Partici pa nts  will  be i de ntifie d as bei n g  of c hil d beari n g p ote ntial pri or  t o virt ual 
visits  a n d a uri ne pre g na nc y test will  be se nt t o t h ose partici pa nts  t o use d uri n g 
t his visit. 
o  
If at Virt ual Visit 1, t he pre g na nc y test has a n i nc o ncl usi ve res ult, t he partici pa nt 
will  be resc he d ule d i n 2 t o 4 wee ks  at w hic h  ti me t he uri ne pre g na nc y test will be 
re peate d. 
1 2  All  partici pa nts  will  be a d mi nistere d  t he R E A L M test t o deter mi ne literac y  (Da vis et al 
1 9 9 3 ). T he w or d list will be dis pla ye d o n t he partici pa nts scree n a n d t he i nter vie wer will 
be a ble t o vis uall y see a n d hear t he partici pa nt sa y eac h w or d o n t he vi de o.  T his face -t o-
face met h o d of o btai ni n g t he R E A L M is c o nsiste nt wit h t he i n - pers o n face-t o-face 
met h o d. 
1 3  T he C M O G cli nicia n will c o n d uct t he tar gete d me dical a n d me dicati o n hist or y. Pr o d uct 
s hi p me nt will  be hel d  u ntil  after t he tar gete d me dical  a n d me dicati o n  hist or y  is c o m plete d 
a n d t he I n vesti gat or a p pr o ves t he partici pa nt t o recei ve t he i n vesti gati o nal pr o d uct.  
o  
O nce t he C M O G cli nicia n c o m pletes t he me dical a n d me dicati o n hist or y 
i nter vie w a n d t heir e val uati o n, t he y will i n p ut t hat data al o n g wit h t he verifie d 
dia g n ostic data (i ncl u di n g t he C A C re gar dless of verificati o n stat us) fr o m t he 
Dia g n ostics s o urce i nt o t he T A S S t o ol t o o btai n a T A S S o utc o me.  T he cli nicia ns 
i n t he C M O G  a n d t he PI are  bli n de d t o t he e ntries ma de b y t he st u d y partici pa nt 
i n t he We b A p p. T he C M O G will o nl y use la b a n d B P data f or t heir T A S S 

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assess me nts t hat has bee n eit her s o urce verifie d or fr o m a st u d y ma n date d test.  If 
t he s o urce d oc u me nt c o ntai ns m ore t ha n o ne val ue f or a para meter, t he C M O G 
will al wa ys use t he m ost rece nt val ue f or t heir assess me nt . T his  pr oce d ure will  
be use d  f or t he Virt ual  Visit  1 a n d Virt ual Visit 2 T A S S assess me nts.  
o  
T he Ce ntral Assess or will c o m pare t he self -selecti o n o utc o me fr o m t he 
partici pa nt  i n We b  A p p  t o t he T A S S  e ntries a n d i nitial o utc o me fr o m t he C M O G 
cli nicia n. 
 F or t h ose partici pa nts pr ocee di n g i nt o t he act ual use p orti o n of t he st u d y: 
F oll o w- u p pr o bes will be as ke d f or a n y discre pa ncies bet wee n T A S S  e ntries 
t hat are o nl y as ke d at t he i nitial T A S S  assess me nt  as well as a n y We b A p p 
use err ors.  
 F or t h ose partici pa nts w h o d o n ot meet t he criteria f or pr ocee di n g i nt o t he  
act ual use p orti o n of  t he st u d y:  F oll o w- u p pr o bes will  be as ke d of a 
partici pa nt f or a n y discre pa ncies bet wee n T A S S  e ntries as well as We b A p p 
use err ors.  
 T he f oll o w- u p q uesti o ns are n ot use d f or a dj ust me nt of t he self - selecti o n 
res ults; t his i nf or mati o n is use d t o deter mi ne t he r o ot ca use of a n y  
discre pa ncies  bet wee n  t he me dical  a n d me dicati o n  hist or y  a n d We b A p p 
e ntries. 
1 4  Partici pa nts will be pr o vi de d wit h st u d y pr oce d ure i nstr ucti o ns a n d i nstr ucti o ns o n h o w t o 
c o m plete  t he e Diar y. N o  i nstr ucti o n will  be pr o vi de d re gar di n g t he use of t he pr o d uct. See 
Secti o n  8. 1  f or a d diti o nal i nf or mati o n o n t he e Diar y. 
1 5  O nce t he partici pa nt has bee n a p pr o ve d t o use t he pr o d uct, t he Ce ntral Pri nci pal 
I n vesti gat or or S u b-I n vesti gat or will a ut h orize a release of t he i nitial or der c o nfir mati o n 
fr o m t he We b A p p  t hat is se nt t o t he Ce ntral De p ot f or  i nitial s hi p me nt of dr u g. T he  date 
t hat t he dr u g is deli vere d t o t he a d dress gi ve n b y t he partici pa nt will be Da y 1. 
o  
All partici pa nts  at Virt ual Visit  1 will  be all o we d t o e nter t he use peri o d of t he 
st u d y pr o vi de d a C M O G  cli nicia n has  n ot deter mi ne d  t hat t he partici pa nt  has  a 
c o n diti o n f or w hic h  treat me nt w o ul d p ose a n u nacce pta ble  ris k (e. g., aller g y t o 
r os u vastati n or a w o ma n w h o is breastfee di n g or pre g na nt). 
 
Use Peri o d   
1 6  T he use peri o d of t he st u d y be gi ns o n t he da y t hat t he pr o d uct is deli vere d t o t he a d dress 
pr o vi de d b y t he partici pa nt.  T he  use peri o d lasts 6- m o nt hs. D uri n g t his peri o d, partici pa nts 
ha ve t he o pti o n t o p urc hase m ore pr o d uct. 
1 7  Partici pa nts  will  nee d  t o utilize  t he e Diar y t o rec or d t he u ni q ue b ottle  I D(s) recei ve d f or 
t his i nitial s hi p me nt a n d a n y s u bse q ue nt re or der s hi p me nts recei ve d t o c o nfir m recei pt of 
deli ver y of t he st u d y dr u g. 

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1 8  Partici pa nts will be i nstr ucte d t o use t he e Diar y t o  rec or d w he n t he y t o o k st u d y dr u g, ha ve 
c ha n ges t o a n y me dicati o ns a n d ha ve  a n y c ha n ges i n healt h  stat us. T he diar y  will be 
re vie we d f or A Es b y a C M O G cli nicia n at t he da y 6 0 a n d da y 1 2 0 p h o ne call ( p h o ne calls 
descri be d i n Ste p 2 2 bel o w) a n d at t he Virt ual Visit 2.  A Es will be f oll o we d t o res ol uti o n.  
See Secti o n  8. 1  f or f urt her details re gar di n g e Diar y. 
1 9  T he ti mi n g f or re or deri n g dr u g f or a 4 5- da y or der a n d a 9 0- da y or der will be after 5 da ys 
fr o m t he date of last deli ver y. E mails will als o be use d t o i nf or m partici pa nts w he n t he y 
s h o ul d re or der. T he y will recei ve a re or der e mail at da y 2 5 f or a 4 5 - da y s u p pl y or der a n d 
at da y 4 5 f or a 9 0- da y s u p pl y or der. Partici pa nts will ha ve a  TA S S assess me nt perf or me d 
d uri n g t he re or der.  Pr o vi de d t he y recei ve a n “ O K t o Use” o utc o me or a n “ As k a D oct or”  
o utc o me a n d i n dicate t he d oct or ga ve  t he m per missi o n t o c o nti n ue treat me nt, t he y ca n 
re or der. H o we ver, t he partici pa nt d oes n ot i nteract wit h a C M O G cli nicia n t o ha ve t heir 
me dical a n d  me dicati o n hist or y assesse d d uri n g re or ders. 
2 0  Beca use partici pa nts i n t he A U S will p urc hase n o n prescri pti o n r os u vastati n calci u m 
o nli ne, t he y will recei ve e C o m merce tra nsacti o nal c o m m u nicati o ns (e mails) t hat o ne 
w o ul d e x pect t o recei ve w he n ma ki n g a n o nli ne p urc hase; t hese will be c o nsiste nt wit h 
t he messa ges pr o vi de d w he n n o n prescri pti o n r os u vastati n is c o m mercialize d.  
Tra nsacti o nal  messa ges  will  i ncl u de c o nfir mati o n  t hat a partici pa nt’s or der was place d, 
s hi p pe d, deli vere d, a n d n otificati o n of eli gi bilit y t o re or der.  I n a d diti o n, s o me 
tra nsacti o nal messa ges will be acc o m pa nie d b y sec o n dar y messa ges rei nf orci n g D F L 
re q uire me nts w hic h i ncl u des a d here nce re mi n ders, re mi n ders t o ha ve t heir c h olester ol 
le vels teste d, re mi n ders t o re vie w a n d be fa miliar wit h t he D F L, ge neral heart healt h 
e d ucati o n, a n d a messa ge t o partici pa nts wit h dia betes a b o ut t he i m p orta nce of ha vi n g a 
d oct or ma na ge t heir bl o o d s u gars. T hese e mails will be se nt t o all st u d y partici pa nts.  T he 
n u m ber a n d fre q ue nc y of tra nsacti o nal e mails se nt t o partici pa nts will var y beca use t he y 
are tri g gere d b y a s pecific e ve nt or acti vit y. If t hat tra nsacti o nal e ve nt or acti vit y d oes n ot 
occ ur, t he partici pa nt will n ot be se nt t he res pecti ve tra nsacti o nal e mail. All e mails will 
c o m pl y wit h t he 2 0 0 3 C o ntr olli n g t he Assa ult of N o n- S olicite d P or n o gra p h y a n d 
Mar keti n g ( C A N- S P A M Act) re q uire me nts.  
2 1  If t he partici pa nt  is u ns ure w here  t o get t heir L D L- C retest d uri n g t he 6-m o nt h  use peri o d, 
t he sa me pr ocess as descri be d i n Ste p 4 will be f oll o we d. 
2 2  D uri n g t he 6- m o nt h use peri o d, t he C M O G cli nicia n will perf or m a tele p h o ne stat us 
c hec k wit h partici pa nts at 6 0 a n d 1 2 0 da ys t o assess a n y c ha n ges i n healt h a n d/ or 
me dicati o ns as well as a n y a d diti o nal st u d y -relate d iss ues ( n o i nstr ucti o n will be pr o vi de d 
re gar di n g t he use of t he pr o d uct).  At a p pr o xi matel y da y 1 6 5, partici pa nts will be calle d 
a n d t he Virt ual  Visit  2 will  be sc he d ule d. D uri n g t his call if a partici pa nt ha d a n L D L-C 
retest, t he y will be as ke d t o c o nfir m if t he y ha ve a verifie d L D L-C retest. 
o  
Refer t o Ste p 6 f or defi niti o n of “ verifie d.”  Verifie d L D L -C retest val ue i ncl u des  
res ults fr o m a D oct or’s  office  or healt h  scree ni n g w hic h  m ust N O T  be pri or t o t he 
start date of Crest or O T C a n d ha ve a na me t hat matc hes t he partici pa nt’s dri ver’s 

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lice nse or ot her i de ntificati o n wit h a pict ure I D (e. g., sc h o ol I D, militar y I D, 
pass p ort, etc).  
o  
St u d y ma n date d la b testi n g f or Virt ual Visit 2 will f oll o w t he sa me pr ocess as 
descri be d i n Ste p 6 a n d will be re q uire d f or all partici pa nts e xce pt t h ose w h o 
recei ve d a “ D o N ot Use” o utc o me, a n “ As k a D oct or” o utc o me b ut di d n ot 
i n dicate wit hi n t he We b A p p t hat t he d oct or ga ve t he m per missi o n t o c o nti n ue 
treat me nt, per ma ne ntl y disc o nti n ue d st u d y me dicati o n ( partici pa nt or C M O G 
cli nicia n decisi o n) or  wit h dre w fr o m t he st u d y. T he  reas o n is t hat m ost  of t hese 
i n di vi d uals will be off-treat me nt f or a n e xte n de d peri o d of ti me bef ore a st u d y 
ma n date d test c o ul d be perf or me d. 
 
At Virt u al Visit 2  
2 3  If t he Ce ntral  Assess or ca n n ot  verif y  t he L D L - C val ue, Virt ual Visit  2 will  be resc he d ule d 
if t he partici pa nt re q uires a st u d y ma n date d test. 
2 4  W o me n  of c hil d beari n g p ote ntial will  ta ke a uri ne  pre g na nc y test a n d s h o w t he test res ults 
t o t he C M O G cli nicia n via t he vi de o. 
2 5  A n y partici pa nt w h o, o n t heir last or der, ha d a n “ O K t o Use” or “ As k a D oct or” a n d 
i n dicate d t hat t he D oct or  ga ve t he m per missi o n  t o c o nti n ue treat me nt will  c o m plete a 
T A S S fi nal use assess me nt d uri n g t he Virt ual Visit 2.   A n y partici pa nt w h o, o n t heir last 
or der, ha d a “ D o N ot Use” o utc o me or a “ As k a D oct or” o utc o me a n d di d n ot i n dicate t he 
D oct or ga ve t he m per missi o n t o c o nti n ue treat me nt will n ot c o m plete a T A S S fi nal use 
assess me nt d uri n g t he Virt ual Visit 2.  T he re or der assess me nt t hat res ulte d i n a “ D o N ot 
Use” o ut c o me or a n “ As k a D oct or” o utc o me (a n d di d n ot i n dicate t he D oct or ga ve t he m 
per missi o n t o c o nti n ue treat me nt) will be use d as t he partici pa nt’s T A S S fi nal use 
assess me nt a n d fi nal use o utc o me.  
2 6  A n y partici pa nt w h o, o n t heir last or der, ha d a n “ O K t o Use” o utc o me or “ As k a D oct or” 
o utc o me a n d i n dicate d t hat t he d oct or ga ve t he m per missi o n t o c o nti n ue treat me nt will be  
re q uire d t o ha ve a st u d y ma n date d L D L- C retest if t he y d o n ot  ha ve a verifie d s o urce f or 
t heir L D L-C retest(s).  Partici pa nts wit h a st u d y ma n d ate d L D L-C retest will be i nstr ucte d 
b y t he Ce ntral Assess or t o a ns wer “ N o” t o t he L D L retest q uesti o n.  T he Ce ntral 
Assess or will re vie w t he T A S S t o e ns ure t he partici pa nt  e ntere d “ N o” as i nstr ucte d.  If 
t he partici pa nt still e ntere d a n L D L-C fr o m t he st u d y  ma n date d test, t he Ce ntral  Assess or 
will  i nstr uct t he partici pa nt  t o re peat t he T A S S  a n d reiterate t o e nter “ N o” t o t he L D L -C 
retest q uesti o n. T he reas o n f or i nstr ucti n g partici pa nts t o a ns wer “ N o” t o t he retest 
q uesti o n is beca use t he y were i nstr ucte d t o retest a n d di d n ot f oll o w t he D F L or We b A p p 
i nstr ucti o ns f or retesti n g.  Beca use t he We b A p p was desi g ne d t o all o w i n di vi d uals w h o 
d o n ot retest t o c o m plete t he st u d y, all o wi n g s u bjects t o e nter a st u d y ma n date d  test c o ul d 
p ote ntiall y lea d t o i nc orrect o utc o mes a n d, i n a d diti o n, bias t he res ults of t he retest 
c o m plia nce e n d p oi nt.  Partici pa nts w h o  e nter a n L D L - C val ue i nt o t he T A S S  assess me nt  

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t hat is a n i na de q uate res p o nse t o treat me nt will be i nstr ucte d t hr o u g h t he We b A p p t o 
re peat t he L D L -C retest.  If t hese partici pa nts o n t heir  last or der ha ve a n “ O K t o Use” 
o utc o me or “ As k a D oct or” o utc o me a n d i n dicate d t hat t he d oct or ga ve t he m per missi o n 
t o c o nti n ue treat me nt, a st u d y ma n date d L D L- C retest will be re q uire d if t he y d o n ot ha ve 
a verifie d s o urce f or t heir re peat L D L-C retest(s). Partici pa nts w h o e nter Virt ual Visit 2 
wit h a “ D o N ot Use” o utc o me or a n  “ As k a D oct or” o utc o me b ut t he y di d n ot i n dicate t he 
d oct or ga ve t he m per missi o n t o use t he dr u g or wit h dre w or disc o nti n ue d fr o m t he st u d y 
will n ot u n der g o st u d y ma n date d testi n g. 
2 7  T he  C M O G  cli nicia n will  t he n c o n d uct a f oll o w- u p me dical  a n d me dicati o n  hist or y  t o 
deter mi ne if t here were a n y c ha n ges i n healt h d uri n g t he st u d y. 
o  
O nce t he tar gete d me dical a n d me dicati o n hist or y i nter vie w is c o m plete, t he 
C M O G cli nicia n will use t he data o btai ne d  i n t he me dical i nter vie w al o n g wit h 
t he verifie d L D L- C val ue fr o m t he Dia g n ostics s o urce a n d i n p ut t hat data i nt o 
t he We b A p p t o o btai n a C M O G cli nicia n use o utc o me. T he C M O G cli nicia n 
wi ll o nl y e nter a verifie d L D L-C val ue i nt o t he T A S S. If a partici pa nt has 
m ulti ple  verifie d  L D L - C val ues d uri n g t he c o urse of t he use peri o d, t he C M O G 
cli nicia n will e nter  t he m ost rece nt verifie d val ue (t his ca n be “ verifie d s o urce” 
or “ verifie d b y st u d y m a n date d test”).  
o  
T he Ce ntral Assess or will c o m pare t he T A S S fi nal use o utc o me fr o m t he 
partici pa nt t o t he use o utc o me fr o m t he C M O G cli nicia n. F oll o w- u p pr o bes will 
be as ke d of partici pa nts  f or discre pa ncies bet wee n T A S S e ntries  as well as a n y  
use err ors.  T he f oll o w- u p q uesti o ns are n ot use d  f or a dj ust me nt  of t he self- 
selecti o n res ults; t his i nf or mati o n is use d t o deter mi ne t he r o ot ca use of a n y 
discre pa ncies bet wee n t he me dical a n d me dicati o n hist or y a n d We b A p p  e ntries 
or use err ors. 
2 8  T he e Diar y will als o be re vie we d at t he Virt ual Visit 2 f or A Es as well as c o m plia nce 
wit h t he Directi o ns a n d St o p use war ni n gs o n t he D F L. A Es will be f oll o we d t o 
res ol uti o n. T he  C M O G  cli nicia n will  i nstr uct t he partici pa nt  t o ret ur n all s ur pl us st u d y 
dr u g/ pac ka gi n g p urc hase d d uri n g t he st u d y i nt o t he ret ur n pac ka gi n g pr o vi de d at t he 
be gi n ni n g of t he st u d y f or s hi p me nt bac k t o t he st u d y site. T h ose partici pa nts w h o ref use 
t o se n d bac k t heir pill b ottles f or a fi nal pill c o u nt will be gi ve n t he o pti o n t o c o u nt t he 
pills wi t h t he st u d y pers o n nel via vi de o c o nfere nce at Virt ual Visit 2. 
2 9  O nce all q uesti o ns are c o m plete a n d t he partici pa nt has pre pare d t he s hi p me nt of t he st u d y  
dr u g bac k  t o t he st u d y site, t he partici pa nt will  be dis misse d  fr o m t he st u d y visit.  
 
3 0- d a y F oll o w- u p  
3 0  T hirt y da ys p ost -st u d y dr u g disc o nti n uati o n, st u d y staff will c o m plete a f oll o w- u p 
tele p h o ne call t o assess f or p ossi ble A Es.  O nce t his p ost- use p h o ne call is c o m plete a n d 
n o a d diti o nal A Es ha ve bee n re p orte d, t he partici pa nt will ha ve c o m plete d all st u d y 

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pr oce d ures.  All A Es will be f oll o we d t o res ol uti o n via a d diti o nal p h o ne call as re q uire d. 
Partici pa nt  sti pe n d a n d c o m pe nsati o n f or pr o d uct p urc hase will be pr o vi de d u p o n recei pt 
of ret ur ne d st u d y dr u g a n d/ or pr o d uct pac ka gi n g at C o nce ntri cs as well as c o m pleti o n of 
3 0- da y p ost use p h o ne call. 
 
8. 1  
e Di ar y 
T he e Diar y will be use d t o gat her mi ni mal data i n a n u n biasi n g ma n ner a n d is n ot use d t o 
i nstr uct t he partici pa nt o n t he pr o per use of t he dr u g. T he i nf or mati o n gat here d will i ncl u de 
d osi n g ( date/ti me a n d a m o u nt of dr u g ta ke n), A Es (c ha n ges i n healt h), a n d me dicati o n 
c ha n ges.  T he  partici pa nt  will  rec or d t he u ni q ue I D fr o m t he st u d y dr u g b ottle  t o c o nfir m 
recei pt of t he pr o d uct. 
T he e Diar y pr o vi der will pr o vi de a n otificati o n t o  t he st ud y tea m w he n t he y detect n o acti vit y 
i n t he e Diar y f or m ore  t ha n 7 da ys. T his  will  ge nerate a c o m m u nicati o n t o t he partici pa nt fr o m 
t he st u d y staff t o deter mi ne  if (a) t he partici pa nt has a n y q uesti o ns a b o ut usi n g t he e Diar y (re- 
trai ni n g ma y be necessar y) or ( b) t o u n dersta n d if t he partici pa nt is still partici pati n g i n t he 
st u d y. N o a d diti o nal i nf or mati o n will be pr o vi de d be y o n d t he ori gi nal st u d y i nstr ucti o ns f or 
t he diar y. 
At t he 6 0- da y a n d 1 2 0- da y pla n ne d tele p h o ne c o ntacts, t he e Diaries will  be re vie we d t o 
deter mi ne if “ St o p Use” criteria are prese nt a n d t o as k a b o ut a n y c ha n ges i n healt h.  If s o, t he 
C M O G  cli nicia n will  disc uss t he e ntr y wit h  t he partici pa nt  t o deter mi ne  if it meets t he  “ St o p Use” 
defi niti o n . Meeti n g  t he sec o n d c o-pri mar y  e n d p oi nt a n d t he sec o n dar y e n d p oi nt wit h  re gar d t o 
“ St o p Use” war ni n gs re q uires t hat t he partici pa nt i de ntif y t he “ St o p Use” war ni n g. T heref ore, 
s h o ul d a “ St o p Use” war ni n g be i de ntifie d d uri n g t he 6 0 or 1 2 0- da y t o uc h p oi nt, t he 
partici pa nts will  be ma na ge d as f oll o ws:  
•  
If d uri n g t he 6 0 or 1 2 0- da y t o uc h p oi nt, t he partici pa nt v ol u nteers t hat t he y ha d a st o p use 
war ni n g, t he y will  be sc he d ule d f or Virt ual  Visit  2.  Partici pa nts  w h o  self-i de ntif y a “ St o p 
Use” criteri o n will c o m plete all Virt ual Visit 2 pr oce d ures i ncl u di n g a T A S S assess me nt. 
•  
If, o n t he ot her ha n d, t he C M O G bec o mes a ware of a “ St o p Use” criteri o n d uri n g t he 
tele p h o ne call t hat t he partici pa nt  di d n ot i de ntif y, all Virt ual  Visit  2 pr oce d ures  e xce pt a 
partici pa nt  T A S S a n d  st u d y ma n date d test f or L D L-C will be perf or me d. T he  reas o n f or 
n ot re peati n g t he T A S S is t hat t he partici pa nt di d n ot self -i de ntif y t he " St o p Use" 
criteri o n. I nstea d, t he C M O G i de ntifie d t he criteri o n a n d disc usse d wit h t he partici pa nt, 
w hic h c o ul d bias t he partici pa nt’s be ha vi or w he n c o m pleti n g t he T A S S. F or e xa m ple, a 
partici pa nt w h o di d n ot realize t he y s h o ul d ha ve st o p pe d dr u g beca use of se vere m uscle 
s y m pt o ms, ma y a ns wer " yes" t o t his q uesti o n i n t he TA S S a n d be cate g orize d  as a c orrect  
select or w he n, i n realit y, t he y ma y  ha ve a ns were d " n o" t o t his q uesti o n if t he y ha d n ot 
s p o ke n t o a C M O G cli nicia n pri or t o c o m pleti n g t he T A S S. Beca use t he st u d y staff ha d t o 

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i nf or m t he partici pa nt t hat t he y met a “ St o p Use” criteri o n, t he y will be c o nsi dere d a 
fail ure w he n e val uati n g t he sec o n d c o- pri mar y e n d p oi nt relate d t o “ use”. 
•  
Partici pa nts w h o t he C M O G cli nicia ns i de ntif y as ha vi n g e x perie nce d “ St o p Use” criteria 
are c o nsi dere d “ Disc o nti n ue d fr o m St u d y I nter ve nti o n ” a n d n ot a wit h dra wal (refer t o 
Secti o n  7. 1 ). I n ge neral, t he o nl y e ve nts rec or de d i n a n e Diar y or c o m m u nicate d t o t he 
st u d y staff d uri n g a p h o ne c hec k t hat w o ul d res ult i n st u d y me dical pers o n nel i nstr ucti n g 
t he partici pa nt  t o st o p ta ki n g r os u vastati n are “ St o p Use” criteria.  If s uc h a sit uati o n 
occ urs,  t he partici pa nt  will  be classifie d as a disc o nti n uati o n fr o m st u d y i nter ve nti o n d ue 
t o “ A d verse E ve nt” or “ Pre g na nc y” a n d sc he d ule d f or a Virt ual Visit 2. 
 
If a partici pa nt rec or ds a “ D o N ot  Use”  war ni n g i n t heir e Diar y, we  will  n ot  c o ntact t he m. O ur 
i nte nt i n t he A U S is t o kee p i nteracti o ns wit h t he partici pa nts t o a mi ni m u m s o we d o n ot 
i nfl ue nce t he partici pa nt’s  be ha vi ors or bias t he o utc o me of t he st u d y. B y d oi n g t his, we  all o w 
t he real-life be ha vi or t o c o nti n ue i nt o t he ne xt re or der, at w hic h ti me, t he T A S S re or der 
assess me nt w o ul d res ult i n a “ Crest or O T C is n o l o n ger ri g ht f or y o u” messa ge al o n g wit h a 
messa ge t o st o p dr u g a n d c o ntact a d oct or. I n t he A U S, t he partici pa nt will als o be messa ge d 
t o c o ntact t he call ce nter t o sc he d ule Virt ual Visit 2. 
We a p pr oac he d t he assess me nt of t he “ St o p Use” a n d “ D o N ot Use” war ni n gs differe ntl y. I n 
t he D F L, t he “ St o p Use” war ni n gs are  relate d t o pre g na nc y, ac ute r ha b d o m y ol ysis, m y o pat h y 
a n d he patitis, c o n diti o ns f or w hic h st o p pi n g t he dr u g i m me diatel y are critical. I n c o ntrast, t he 
“ D o N ot  Use”  war ni n gs ha ve a m uc h l o wer ris k f or har m if treat me nt is c o nti n ue d f or a peri o d 
f oll o wi n g t he e ve nt. Prescri pti o n Crest or 5 m g is act uall y i n dicate d f or a n u m ber of t he “ D o 
N ot Use” criteria. W hile we wa nt t o see partici pa nts wit h a “ D o N ot Use” war ni n g st o p dr u g 
i m me diatel y, s h o ul d t he y c o nti n ue f or a peri o d of ti me pri or t o c o m pleti n g a T A S S re or der 
assess me nt, t he li keli h o o d of har m re mai ns l o w.  
8. 2  
Effic ac y  Assess me nts  
T he  efficac y of n o n prescri pti o n r os u vastati n will  be assesse d  as a c o-pri mar y  e n d p oi nt a n d i n 
 D uri n g t he use peri o d of t he  st u d y, partici pa nts will be t ol d t o 
retest t heir L D L -C.  F or  t h ose w h o d o n ot retest or ha ve u n verifie d s o urce f or t he L D L - C data 
i n p utte d i nt o t he We b  A p p,  a st u d y ma n date d test will be  re q uire d f or Virt ual  Visit 2  f or t h ose 
partici pa nts descri be d i n Secti o n  8 , Step 2 2. T he L D L -C data will be use d t o assess t he 
o verall res p o nse t o treat me nt.  
8. 3  
S afet y  Assess me nts  
Pla n ne d ti me p oi nts f or all safet y assess me nts  are pr o vi de d i n t he S o A.  
8. 3. 1  
P h ysic al  E x a mi n ati o ns  
T here  will  be  n o p h ysical e xa mi nati o ns perf or me d  as part of  t his st u d y. 
C CI

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8. 3. 2  
Vit al  Si g ns  
Bl o o d press ure meas ure me nt  will  be pr o vi de d at st u d y e ntr y a n d ma y  be perf or me d  t hr o u g h a 
l ocal testi n g site (e. g., retail-base d B P  ki os ks) if t he s u bject di d n ot pr o vi de a verifie d  s o urce. 
See Secti o n  8 , Ste p 6 f or f urt her details. 
8. 3. 3  
Electr oc ar di o gr a ms  
N o  E C Gs  will  be perf or me d as  part of  t his st u d y. 
8. 3. 4  
Cli nic al  S afet y  L a b or at or y  Assess me nts  
At Virt ual Visit 1, if t he s u bject ca n n ot pr o vi de verificati o n of t he s o urce of t heir la b orat or y 
n u m bers or if t he  s o urce is greater  t ha n 1 2 m o nt hs ( + 3-m o nt h  wi n d o w) pri or t o  c o m pleti n g t he 
We b  A p p, t he n t he s u bject will be se nt f or st u d y ma n date d  testi n g f or Tri gl yceri des,  T C,  
L D L -C, H D L - C a n d, if necessar y, hs-C R P. If s u bject is  n ot a ble t o get t o o ne of t he l ocal 
testi n g sites, t he Call Ce nter ca n direct t he m t o or der a h o me test kit. S u bjects will n ot pa y f or 
st u d y ma n date d testi n g. S u bjects als o ha ve t he o pti o n of resc he d uli n g t heir a p p oi nt me nt t o 
l ocate t heir verifie d s o urce. T here will be n o o pti o n t o o btai n C A C i ma gi n g i n t he e ve nt a 
s u bject i n p uts t his i nf or mati o n i nt o t he We b  A p p a n d d oes n ot ha ve a verifie d s o urce at t he 
virt ual site visit.  T his C A C data will be d oc u me nte d as “ u n verifie d” b ut will be c o nsi dere d 
acce pta ble f or use b y t he C M O G cli nicia n f or t heir T A S S assess me nt if necessar y.  A missi n g 
C A C sc ore w o ul d n ot e xcl u de a partici pa nt fr o m pr ocee di n g t o partici pate i n t he A U S. ( N ote 
t hat is hi g hl y u nli kel y t hat a partici pa nt w o ul d u n dersta n d a C A C sc ore a n d e nter a vali d sc ore 
i nt o t he We b  A p p wit h o ut ha vi n g ha d t he i ma gi n g test.) W o me n of c hil d beari n g p ote ntial will  
ta ke a n o ver-t he-c o u nter uri ne pre g na nc y test pr o vi de d b y t he C R O pri or t o t he virt ual visit. At  
Virt ual  Visit 2, partici pa nts will  be as ke d t o verif y t he L D L-C e ntere d i nt o t he We b  A p p. If 
t he partici pa nts di d n ot pr o vi de verificati o n or di d n ot retest, t he n t he partici pa nt will be se nt  
f or st u d y ma ndate d testi n g. See Secti o n 8,  Ste p 2 2 f or a descri pti o n re gar di n g w hic h 
partici pa nts are se nt  f or st u d y ma n date d testi n g. W o me n of c hil d beari n g p ote ntial will ta ke 
a n ot her o ver-t he-c o u nter uri ne pre g na nc y test pr o vi de d b y t he C R O.  
8. 3. 5  
Ot her  S afet y  Assess me nts  
W he n  t he partici pa nt  c o m pletes  t he We b  A p p  t o re or der, t he We b  A p p  will  as k q uesti o ns a b o ut 
certai n c ha n ges i n healt h.  C ha n ges i n healt h will als o be assesse d at eac h i nteri m p h o ne call.  
8. 4  
A d verse  E ve nts  a n d  Seri o us  A d verse  E ve nts  
T he  Pri nci pal  I n vesti gat or ( PI) is res p o nsi ble f or e ns uri n g t hat all staff i n v ol ve d i n t he st u d y 
are fa miliar wit h t he c o nte nt of t his secti o n. 
T he  defi niti o ns of a n A E or seri o us A E ( S A E) ca n be f o u n d i n A p pe n di x B.  

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If t he partici pa nt re p orts a n A E,  t he i n vesti gat or a n d a n y desi g nees  are res p o nsi ble f or 
detecti n g, d oc u me nti n g, a n d rec or di n g e ve nts t hat meet t he defi niti o n of a n  A E.  
8. 4. 1  
Ti me  Peri o d  a n d  Fre q ue nc y  f or C ollecti n g  A E  a n d  S A E  I nf or m ati o n 
A d verse E ve nts will be c ollecte d fr o m t he ti me of si g nat ure of i nf or me d c o nse nt f or m , 
t hr o u g h o ut t he use peri o d  a n d 3 0- da ys after st u d y dr u g c o m pleti o n/ disc o nti n uati o n. Al l A Es 
will be f oll o we d t o res ol uti o n.  
S A Es  will  be  rec or de d fr o m t he ti me of si g ni n g of  i nf or me d c o nse nt  f or m. 
If t he i n vesti gat or bec o mes a ware of a n S A E wit h a s us pecte d ca usal relati o ns hi p t o t he 
i n vesti gati o nal me dici nal pr o d uct t hat occ urs after t he e n d of t he cli nical st u d y i n a partici pa nt  
treate d b y hi m  or her, t he i n vesti gat or s hall, wit h o ut u n d ue dela y, re p ort t he S A E t o t he 
s p o ns or. 
8. 4. 2  
F oll o w -u p  of  A Es  a n d  S A Es  
All  A Es will be f oll o we d t o res ol uti o n.  Astra Ze neca retai ns t he ri g ht t o re q uest a d diti o nal 
i nf or mati o n f or a n y partici pa nt wit h  o n g oi n g A E(s)/ S A E(s)  at t he e n d of t he st u d y, if j u d ge d 
necessar y.  
A d verse  e ve nt  v ari a bles  
T he  f oll o wi n g varia bles  will  be c ollecte d f or  eac h A E : 
•  
A E  ( ver bati m) 
•  
T he date w he n  t he A E starte d  a n d st o p pe d 
•  
Se verit y  
•  
W het her t he A E is  seri o us or n ot  
•  
I n vesti gat or ca usalit y rati n g a gai nst t he I n vesti gati o nal Pr o d uct(s) ( yes or n o)  
•  
Acti o n ta ke n wit h  re gar d t o I n vesti gati o nal Pr o d uct(s)  
•  
A E  ca use d partici pa nt’s wit h dra wal  fr o m st u d y ( yes or n o)  
•  
O utc o me 
 
I n a d diti o n, t he f oll o wi n g varia bles  will be  c ollecte d f or S A Es:  
•  
Date  A E  met  criteria f or SA E  
•  
Date  i n vesti gat or beca me  a ware of SA E  
•  
A E  is seri o us d ue t o 
•  
Date of  h os pitalizati o n  

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•  
Date of  disc har ge  
•  
Pr o ba ble ca use of deat h  
•  
Date of  deat h  
•  
A ut o ps y perf or me d  
•  
Ca usalit y  assess me nt i n relati o n  t o St u d y pr oce d ure(s)  
•  
Ca usalit y  assess me nt  t o ot her me dicati o n  
 
8. 4. 3  
C a us alit y  C ollecti o n  
T he  i n vesti gat or s h o ul d assess ca usal relati o ns hi p bet wee n I n vesti gati o nal Pr o d uct ( b ot h dr u g 
a n d s oft ware c o nstit ue nt) a n d eac h A E, a n d a ns wer ‘ yes’ or ‘ n o’ t o t he q uesti o n ‘ A E ca use d b y 
I P?’ 
F or S A Es, i n a d diti o n t o assess me nt of ca usal relati o ns hi p wit h I n vesti gati o n pr o d uct ( b ot h 
dr u g a n d s oft ware c o nstit ue nt), ca usal relati o ns hi p s h o ul d als o be assesse d f or ot her 
me dicati o n  a n d st u d y pr oce d ures. N ote  t hat f or S A Es  t hat c o ul d be ass ociate d  wit h  a n y st u d y 
pr oce d ure t he ca usal relati o ns hi p is i m plie d as ‘ yes.’  
A g ui de t o t he i nter pretati o n of t he ca usalit y q uesti o n is f o u n d i n A p pe n di x B  t o t he Cli nical 
St u d y Pr ot oc ol ( C S P).  
8. 4. 4  
A d verse  E ve nts  B ase d  o n  Si g ns  a n d  S y m pt o ms  
All  A Es  s p o nta ne o usl y re p orte d b y t he partici pa nt or re p orte d i n res p o nse t o t he o pe n q uesti o n 
fr o m t he st u d y site staff: ‘ Ha ve y o u ha d a n y c ha n ges i n healt h si nce t he pre vi o us visit/ y o u 
were last as ke d?’, re veale d b y o bser vati o n, recei ve d b y C R O via e mail t hat is tri g gere d fr o m 
t he We b A p p d ue t o partici pa nt res p o nse d uri n g re or der t o o ne of t he T A S S q uesti o ns bel o w, 
or rec or de d i n t he e Diar y will be c ollecte d a n d rec or de d i n t he e C R F. Certai n a ns wers i n t he 
We b  A p p f or re or der assess me nt ma y als o be c ollecte d as  A Es.   T hese i ncl u de t he f oll o wi n g 
q uesti o ns:  
•  
Ha ve  y o u e ver ha d a n y of  t he f oll o wi n g: heart  attac k, str o ke,  o perati o n or pr oce d ure  o n 
y o ur heart, peri p heral arter y disease ( P A D)?  
•  
Ha ve  y o u bee n t ol d b y a d oct or t hat  y o u  ha ve ki d ne y disease  or si nce y o u starte d ta ki n g 
Crest or O T C,  ha ve y o u bee n  t ol d b y a d oct or t hat y o ur ki d ne y disease  has g otte n w orse? 
•  
Ha ve  y o u ha d a n y ne w li ver pr o ble ms ( u p per bell y  pai n, dar k uri ne, or yell o wi n g of s ki n 
or w hites of y o ur e yes)? 
•  
Ha ve  y o u ha d a n y ne w, se vere,  a n d u ne x plai ne d m uscle  pai n, te n der ness, or wea k ness?  
 

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W he n c ollecti n g A Es, t he rec or di n g of dia g n oses is preferre d ( w he n p ossi ble) t o rec or di n g a 
list of si g ns a n d s y m pt o ms. H o we ver, if a dia g n osis is k n o w n a n d t here are ot her si g ns or 
s y m pt o ms t hat are n ot ge nerall y  part  of t he dia g n osis, t he dia g n osis a n d eac h si g n or s y m pt o m 
will be rec or de d se paratel y.  
Partici pa nts  w h o  re p ort A Es  wit h  s y m pt o ms s u g gesti ve of a se vere m y o pat h y, r ha b d o m y ol ysis 
or li ver i nj ur y will be referre d t o a d oct or or a n e mer ge nc y r o o m f or i m me diate care.  
8. 4. 5  
A d verse  E ve nts  B ase d  o n  E x a mi n ati o ns  a n d  Tests  
T he  res ults fr o m t he C S P  ma n date d la b orat or y tests a n d vital  si g ns will  be s u m marize d i n t he 
Cli nical St u d y Re p ort ( C S R).  
Deteri orati o n as c o m pare d t o baseli ne i n pr ot oc ol - ma n date d la b orat or y val ues, s h o ul d o nl y be 
re p orte d as A Es if t he y f ulfill a n y of t he S A E criteria, are t he reas o n f or disc o nti n uati o n of 
treat me nt wit h  t he i n vesti gati o nal pr o d uct or are c o nsi dere d t o be cli nicall y rele va nt as j u d ge d 
b y t he i n vesti gat or ( w hic h ma y i ncl u de b ut n ot li mite d t o c o nsi derati o n as t o w het h er 
treat me nt or n o n-pla n ne d visits were re q uire d).  
If deteri orati o n  i n a la b orat or y val ue/ vital si g n is ass ociate d  wit h  cli nical si g ns a n d s y m pt o ms, 
t he si g n or s y m pt o m will be re p orte d as a n A E a n d t he ass ociate d la b orat or y res ult/ vital si g n 
will be c o nsi dere d as a d diti o nal i nf or mati o n. W here ver p ossi ble t he re p orti n g i n vesti gat or 
uses t he cli nical, rat her t ha n t he la b orat or y ter m (e. g., a ne mia vers us l o w he m o gl o bi n   val ue). 
I n t he a bse nce of cli nical si g ns or s y m pt o ms, cli nicall y rele va nt deteri orati ons i n n o n- 
ma n date d para meters s h o ul d be re p orte d as A E(s).  
A n y  ne w or a g gra vate d  cli nicall y rele va nt a b n or mal me dical  fi n di n g as c o m pare d  wit h  t he 
baseli ne assess me nt will be re p orte d as a n  A E u nless u ne q ui v ocall y relate d t o t he disease 
u n der st u d y. 
8. 4. 6  
Re p or ti n g of  Seri o us  A d verse  E ve nts  
All  S A Es  ha ve t o be re p orte d, w het her or n ot c o nsi dere d  ca usall y relate d t o t he i n vesti gati o nal 
pr o d uct, or t o t he st u d y pr oce d ure(s). All S A Es will be rec or de d i n t he e C R F.  
If a n y S A E  occ urs i n t he c o urse of t he st u d y, t he n i n vesti gat ors or ot her st u d y site pers o n nel 
i nf or m t he a p pr o priate Astra Ze neca re prese ntati ves wit hi n o ne da y  i.e., i m me diatel y b ut n o 
l ater t h a n 2 4 h o urs of w he n he or s he bec o mes a ware of it. 
T he  desi g nate d Astra Ze neca  re prese ntati ve w or ks wit h  t he i n vesti gat or t o e ns ure t hat all t he 
necessar y  i nf or mati o n is pr o vi de d t o t he Astra Ze neca  Patie nt  Safet y  data  e ntr y site wit hi n 1 
c ale n d ar d a y of i nitial recei pt f or fatal a n d life -t hreate ni n g e ve nts a n d wit hi n 5 c ale n d ar 
d a ys of i nitial recei pt f or all ot her S A Es.  

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F or fatal  or life-t hreate ni n g A Es  w here  i m p orta nt or rele va nt i nf or mati o n is missi n g, acti ve 
f oll o w- u p is u n derta ke n i m me diatel y. I n vesti gat ors or ot her st u d y site pers o n nel i nf or m 
Astra Ze neca re prese ntati ves of a n y f oll o w - u p i nf or mati o n o n a pre vi o usl y re p orte d S A E 
wit hi n o ne cale n dar da y i.e., i m me diatel y b ut n o l ater t h a n 2 4 h o urs of w he n he or s he 
bec o mes a ware of it.  
All  S A Es  will  be rec or de d i n t he E D C  s yste m.  I n vesti gat ors or ot her st u d y site pers o n nel will 
se n d rele va nt C R F m o d ules b y fa x t o t he desi g nate d Astra Ze neca re prese ntati ve.  
F or  f urt her g ui da nce o n t he  defi niti o n  of a S A E,  see A p pe n di x B  of t he C S P.  
T he  refere nce d oc u me nt f or defi niti o n  of e x pecte d ness/liste d ness  is t he U S PI  f or Crest or  
(Astra Ze neca P har mace uticals L P 2 0 2 1 ).  
8. 4. 6. 1  
Re p orti n g  of A Es/ S A Es  i n Rel ati o n  t o C O VI D -1 9  
All  A Es/ S A Es s h o ul d be re p orte d i n li ne wit h i nstr ucti o ns f or safet y re p orti n g d oc u me nte d i n 
t he C S P. F or partici pa nts e x perie nci n g si g ns a n d s y m pt o ms i n dicati n g a n i nfecti o n, a n atte m pt 
will  be ma de  t o deter mi ne  w het her t he C or o na vir us 2 0 1 9 ( C O VI D - 1 9) vir us is t he i nfecti o us 
or ga nis m, a n d t he A E will be rec or de d acc or di n gl y. If a partici pa nt prese nts wit h cli nical si g ns 
a n d s y m pt o ms s u g gesti ve of C O VI D- 1 9, a test will be re q ueste d w here p ossi ble. If  t he test is 
p ositi ve, rec or d “ C O VI D -1 9 p ositi ve” i n t he A E Fiel d.  
If a test has n ot bee n perf or me d or res ult is ne gati ve, a d diti o nal q uesti o ns will be as ke d a b o ut 
c o ntact wit h s o me o ne p ositi ve f or C O VI D - 1 9 or wit h C O VI D 1 9 s y m pt o ms a n d ti mi n g 
ar o u n d o nset of s y m pt o ms. If eit her q uesti o n is tr ue, rec or d “ C O VI D- 1 9 s us pecte d” i n t he 
A d verse E ve nt  Fiel d.  If t he cli nicia n has ot her c o nc urre nt  dia g n oses f or t he partici pa nt’s  si g ns 
a n d s y m pt o ms (e. g., p ne u m o nia), t hese will be rec or de d as se parate A Es.  
8. 4. 7  
Pre g n a nc y  
All  pre g na ncies  a n d o utc o mes of pre g na nc y s h o ul d be re p orte d t o Astra Ze neca  e xce pt f or: 
•  
If t he pre g na nc y is disc o vere d bef ore t he st u d y partici pa nt  has recei ve d a n y  st u d y dr u g  
•  
Pre g na ncies  i n t he part ner of male  partici pa nts  
 
8. 4. 7. 1  
M ater n al  E x p os ure  
If a partici pa nt  bec o mes  pre g na nt d uri n g t he c o urse of t he st u d y, i n vesti gati o nal pr o d uct s h o ul d 
be disc o nti n ue d i m me diatel y . 
Pre g na nc y itself is n ot re gar de d as a n A E u nless t here is a s us pici o n t hat t he i n vesti gati o nal 
pr o d uct u n der st u d y ma y ha ve i nterfere d wit h t he effecti ve ness of a c o ntrace pti ve me dicati o n. 
C o n ge nital a b n or malities/ birt h defects a n d s p o nta ne o us miscarria ges s h o ul d be re p orte d a n d 

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ha n dle d as S A Es. Electi ve a b orti o ns wit h o ut c o m plicati o ns s h o ul d n ot be ha n dle d as A Es. T he 
o utc o me of all pre g na ncies (s p o nta ne o us miscarria ge,  electi ve ter mi nati o n, ect o pic pre g na nc y, 
n or mal birt h,  or c o n ge nital a b n or malit y) s h o ul d be f oll o we d u p a n d d oc u me nte d e ve n if t he 
partici pa nt was disc o nti n ue d fr o m t he st u d y. 
If a n y pre g na nc y occ urs d uri n g t he c o urse of t he st u d y, t he n t he i n vesti gat or or ot her st u d y site 
pers o n nel i nf or ms t he a p pr o priate  Astra Ze neca re pre se ntati ves wit hi n 1 da y i.e., i m me diatel y 
b ut n o l ater t h a n 2 4 h o urs of w he n he or s he bec o mes a ware of it.  
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca  Patie nt Safet y  data  e ntr y site wit hi n  1 or 5 
cale n dar da ys f or S A Es (see Secti o n  8. 4. 6 ) a n d wit hi n 3 0 da ys f or all ot her pre g na ncies. 
T he  sa me ti meli nes a p pl y w he n  o utc o me i nf or mati o n is a vaila ble. 
T he  data p oi nts re q uire d t o be c ollecte d i n Astra Ze neca’s  P R E G R E P  m o d ule a n d P R E G O U T 
m o d ule will be use d t o re p ort pre g na nc y a n d pre g na nc y o utc o me via t he pre g na nc y C R F 
m o d ules or a pre g na nc y f or m.  
8. 4. 8  
Me dic ati o n  Err or 
If a me dicati o n  err or occ urs  i n t he c o urse of t he st u d y, t he n t he i n vesti gat or or ot her st u d y  site 
pers o n nel i nf or ms t he  a p pr o priate  Astra Ze neca re prese ntati ves wit hi n 1 da y i.e., i m me diatel y 
b ut n o later t ha n 2 4 h o urs of w he n he or s he bec o mes a ware of it.  
T he  desi g nate d Astra Ze neca  re prese ntati ve w or ks wit h  t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is c o m plete d wit hi n 1 (I nitial Fatal/ Life-T hreate ni n g or f oll o w -u p 
Fatal/ Life -T hreate ni n g) or 5  ( ot her seri o us i nitial a n d f oll o w-u p) cale n dar da ys if t here is a n 
S A E ass ociate d  wit h  t he me dicati o n  err or (see Secti o n 8. 4. 6 ) a n d wit hi n  3 0 da ys f or all ot her 
me dicati o n err ors.  
T he  defi niti o n of a Me dicati o n Err or  ca n be f o u n d i n A p pe n di x B .  
8. 4. 9  
S oft w are  as  a C o nstit ue nt  P art  
A n i n vesti gati o nal s oft ware as a c o nstit ue nt part of a c o m bi nati o n pr o d uct is i ncl u de d i n t his 
st u d y. A n y  A Es  a n d/ or a n y S A Es  re p orte d i n t his st u d y will  u n der g o ca usalit y assess me nt  b y 
t he i n vesti gat or f or ca usal relati o ns hi p wit h t he i n vesti gati o nal pr o d uct, i ncl usi ve of b ot h t he 
dr u g a n d s oft ware c o nstit ue nts. If a ca usal relati o ns hi p wit h t he s oft ware  is s us pecte d f or a n 
A E a n d/ or a n S A E,  it will  be d oc u me nte d wit hi n  t he A E a n d/ or S A E  re p ort. All  S A E  re p orts 
w hic h meet t he defi niti o n of a n I N D safet y re p ort will be s u b mitte d t o healt h a ut h orities 
acc or di n g t o l ocal re g ulati o ns. 

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8. 5  
O ver d ose  
Base d  o n data fr o m Crest or  cli nical pr o gra m, a n y d ose of 8 0 m g  or a b o ve i n a 2 4- h o ur peri o d 
will be c o nsi dere d a n o ver d ose. 
T here  is n o s pecific treat me nt i n t he e ve nt of o ver d ose. I n t he e ve nt of o ver d ose, t he patie nt 
s h o ul d be treate d s y m pt o maticall y, a n d s u p p orti ve meas ures i nstit ute d as re q uire d. 
He m o dial ysis  d oes n ot si g nifica ntl y e n ha nce t he cleara nce  of r os u vastati n. 
•  
A n  o ver d ose wit h  ass ociate d  A Es  is rec or de d as t he A E  dia g n osis/s y m pt o ms  o n t he 
rele va nt A E m o d ules i n t he e C R F a n d o n t he O ver d ose e C R F m o d ule. 
•  
A n  o ver d ose wit h o ut ass ociate d  s y m pt o ms is o nl y re p orte d o n t he O ver d ose e C R F m o d ule  
 
If a n o ver d ose o n a n Astra Ze neca  st u d y dr u g occ urs i n t he c o urse of  t he st u d y, t he i n vesti gat or 
or ot her st u d y site pers o n nel i nf or m a p pr o priate Astra Ze neca  re prese ntati ves i m me diatel y, b ut 
n o l ater t h a n 2 4 h o urs of w he n he or s he bec o mes a ware of it.  
T he desi g nate d Astra Ze neca re prese ntati ve w or ks wit h t he i n vesti gat or t o e ns ure t hat all 
rele va nt i nf or mati o n is pr o vi de d t o t he Astra Ze neca  Patie nt Safet y  data  e ntr y site wit hi n  1 or 5 
cale n dar da ys  f or o ver d oses ass ociate d  wit h  a n S A E (see  Secti o n 8. 4. 6 ) a n d wit hi n  3 0 da ys f or 
all ot her o ver d oses. 
8. 6  
H u m a n  Bi ol o gic al  S a m ples  
Partici pa nts  ma y  use a l ocal testi n g site or a h o me test kit f or la bs  a n d w o me n  of c hil d beari n g 
p ote ntial will ta ke a n at h o me uri ne pre g na nc y test. N o h u ma n bi ol o gical sa m ples will be 
st ore d as part  of t his st u d y. See  Secti o n  8  f or f urt her details.  
8. 6. 1  
P h ar m ac o ki netics  
P har mac o ki netic  para meters  are n ot e val uate d i n t his st u d y. 
8. 6. 2  
P h ar m ac o d y n a mics  
P har mac o d y na mics are e val uate d as part of t he L D L - C re d ucti o n efficac y e val uati o ns.  
8. 7  
H u m a n  Bi ol o gic al  S a m ple  Bi o m ar kers  
8. 7. 1  
C ollecti o n  of  M a n d at or y  Sa m ples  f or Bi o m ar ker An al ysis  
T here  will  be  n o ma n dat or y c ollecti o n of sa m ples f or bi o mar ker  a nal ysis i n t his st u d y. 
8. 7. 2  
C ollecti o n  of  Opti o n al  Bi o m ar ker Sa m ples  
T here  will  be n o c ollecti o n of o pti o nal bi o mar kers  sa m ples i n t he st u d y. 

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8. 7. 3  
Ot her  St u d y -Rel ate d  Bi o m ar ker  Rese arc h 
Bi o mar ker  researc h is n ot  a p plica ble i n t his st u d y. 
8. 8  
O pti o n al  Ge n o mics  I niti ati ve S a m ple  
O pti o nal Ge n o mics I nitiati ve researc h is n ot a p plica ble i n t his st u d y. 
8. 9  
He alt h  Ec o n o mics  O R  Me dic al  Res o urce  Utiliz ati o n  a n d  He alt h 
Ec o n o mics  
N ot a p plica ble t o t his st u d y. 
9  
S T A TI S TI C A L  C O N SI D E R A TI O N S  
9. 1  
St atistic al  H y p ot heses  
Statistical h y p ot heses  will be  teste d f or all of t he c o-pri mar y e n d p oi nts  f or t he st u d y. T hese 
e n d p oi nts are defi ne d i n detail  i n Secti o n  9. 4. 2. 1 . F or eac h  of t he use c o-pri mar y  e n d p oi nts, 
na mel y, t he O verall C orrect I nitial T A S S O utc o me a n d t he O verall C orrect Fi nal Use 
O utc o me, t he bel o w n ull h y p ot hesis will be rejecte d i n fa v or of t he alter nati ve if t he l o wer 
b o u n d of t he t w o-si de d 9 5 % e xact bi n o mial (i.e., Cl o p per-Pears o n) CI is  greater  t ha n 8 5 %. 
H 0: P ≤ 8 5 % vs. H1: P > 8 5 %  
F or t he t hir d c o - pri mar y e n d p oi nt, P C F B i n verifie d L D L- C t o Visit 2, t he bel o w n ull 
h y p ot hesis will  be rejecte d i n fa v or of t he alter nati ve  if t he u p per b o u n d of t he t w o-si de d 9 5 % 
c o nfi de nce i nter val o n t he mea n P C F B i n verifie d L D L -C t o Visit 2 is less t ha n -1 5 %.  
H 0: μ ≥ - 1 5 % vs. H1: μ  < -1 5 %  
w here  µ is  t he mea n  P C F B  i n verifie d  L D L - C t o Visit 2.  
9. 2  
S a m ple  Size  Deter mi n ati o n  
T he sa m ple size is base d o n p o weri n g t he st u d y f or t he c o - pri mar y e n d p oi nts. T he e val uati o n 
of t he first c o -pri mar y e n d p oi nt o n t he O verall C orrect I nitial T A S S O utc o me will ha ve a 
sa m ple size of a p pr o xi matel y 1 2 2 0; h o we ver, n ot all of t hese partici pa nts ma y ha ve a n 
O verall C orrect I nitial T A S S O utc o me. As part of t he pri mar y a nal ysis of t his e n d p oi nt, a n y 
partici pa nts  wit h  a missi n g  O verall  C orrect  I nitial T A S S O utc o me  will  be  i m p ute d usi n g w orst 
case i m p utati o n (i.e., as i nc orrect). As s uc h, it is u n k n o w n e xactl y h o w t he tr ue self- selecti o n 
rate will  be affecte d  base d  o n t his i m p utati o n. T heref ore, t he res ulti n g p o wer ass u mi n g vari o us 
tr ue self-selecti o n rates i n or der t o de m o nstrate t hat t he L B of t he 9 5 % e xact bi n o mial 
c o nfi de nce i nter val ( CI) is greater t ha n 8 5 % wit h a sa m ple of a p pr o xi matel y 1 2 2 0 partici pa nts 
is prese nte d i n t he ta ble bel o w: 

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Tr ue  Self -Selecti o n  
Rate  
 
P o wer  
Tr ue Self -Selecti o n  
Rate  
 
P o wer  
8 8. 2 4 %  
9 0 %  
8 8. 5 7 %  
9 5 %  
8 8. 3 0 %  
9 1 %  
8 8. 6 7 %  
9 6 %  
8 8. 3 5 %  
9 2 %  
8 8. 7 8 %  
9 7 %  
8 8. 4 2 %  
9 3 %  
8 8. 9 3 %  
9 8 %  
8 8. 4 9 %  
9 4 %  
9 0. 0 0 %  
> 9 9 %  
 
E val uati o n of t he sec o n d c o- pri mar y e n d p oi nt o n t he O verall C orrect Fi nal Use O utc o me will 
ha ve a sa m ple size of at least 5 0 0 partici pa nts.   A sa m ple size of 5 0 0 partici pa nts w o ul d 
pr o vi de at least 9 0 % p o wer  t o de m o nstrate t hat t he l o wer b o u n d of t he 9 5 %  e xact bi n o mial CI 
is greater t ha n  8 5 % f or t he fi nal use e n d p oi nt, ass u mi n g t hat t he tr ue c orrect  fi nal use o utc o me 
rate is 9 0 %. It is a ntici pate d t hat at  least 4 5 0 partici pa nts will be i ncl u de d i n t he e val uati o n of 
t he t hir d c o- pri mar y e n d p oi nt of P C F B i n verifie d L D L-C t o Visit 2. Ass u mi n g a tr ue mea n 
P C F B of - 2 5 % wit h a sta n dar d de viati o n of 2 5 %, a sa m ple size of 4 5 0 partici pa nts w o ul d 
pr o vi de greater t ha n 9 9 % p o wer t o de m o nstrate t hat t he u p per b o u n d of t he t w o-si de d 9 5 % 
c o nfi de nce i nter val o n t he mea n P C F B i n verifie d L D L -C t o Visit 2 is less t ha n -1 5 %.  
It is e x pecte d t hat a p pr o xi matel y 8 0, 0 0 0 c o ns u mers will c o ntact t he Call Ce nter f or pre- 
scree ni n g i n res p o nse t o a d vertisi n g.  Tra diti o nal (i.e., tele visi o n, pri nt) a n d di gital  a d vertisi n g 
a p pr oac hes will be utilize d f or recr uit me nt. T he ta ble bel o w s u m marizes t he esti mates a n d 
perce nta ge  dr o ps at eac h ste p fr o m t he i nitial call i nt o t he Call  Ce nter  t hr o u g h c o m pleti o n of 
t he st u d y. 
T a ble  3 
Esti m ate d N u m ber  of S u bjects/ P artici p a nts  b y  St u d y  St a ge  
Calls  i nt o Call Ce nter  
Esti mate d  8 0, 0 0 0 calls 
Se nt  t he We b  Li n k  
  Ass u mes:  
  Pre -scree n Fail rate = 2 4 %  
  Q ualifie d Ref use d  rate =  8 %  
Esti mate d  5 4, 4 0 0  s u bjects 
C o m plete  t he We b  Li n k  ( 6 6 %) 
Esti mate d  3 5, 9 0 0 s u bjects 
Q ualif y  as “ O k t o Use” ( ~  5 %)  
Esti mate d  1, 8 0 0 s u bjects 
Sc he d ule  Virt ual  Visit  1  ( 8 5 %) 
Esti mate d  1, 5 2 5  s u bjects 
E nr olle d  – C o m plete  c o nse nt  at Virt ual  Visit 1 
( 8 0 %) 
Esti mate d  1, 2 2 0 partici pa nts  
E nter  Use P hase of  t he St u d y ( 8 3 %) 
Esti mate d  1, 0 0 0 partici pa nts  
Wit h dra wals/ L ost -t o f oll o w-u p  d uri n g  use ( ~ 5 0 %) 
Esti mate d 5 0 0  partici pa nts  

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E val ua ble partici pa nts * 
Esti mate d 5 0 0  partici pa nts  
* E val ua ble f or t he sec o n d c o-pri mar y e n d p oi nt, O verall C orrect Fi nal Use O utc o me  
 
N ote : “ E nr olle d” is defi ne d as a partici pa nt’s a gree me nt t o partici pate i n a cli nical st u d y 
f oll o wi n g c o m pleti o n of t he i nf or me d c o nse nt f or m (I C F) pr ocess. S u bjects w h o are pre- 
scree ne d f or t he p ur p ose of deter mi ni n g eli gi bilit y f or t he st u d y b ut d o n ot si g n c o nse nt, are 
defi ne d as “ pre -scree n fail ures.” See Secti o n  9. 3  f or f urt her detail o n t he defi niti on of pre- 
scree n a n d scree n fail ures. 

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9. 3  
P o p ul ati o ns  f or A n al yses  
T he  f oll o wi n g p o p ulati o ns are defi ne d:  
T a ble  4 
P o p ul ati o ns  f or A n al ysis  
P o p ul ati o n/ A n al ysis  set 
Descri pti o n  
Pre -Scree ne d  
Pre -Scree ne d  are all s u bjects w h o c o m plete t he  i nitial pre -
scree ner eit her o nli ne or b y calli n g t he Call Ce nter. 
Pre -Scree n  Fail ures  
Pre -Scree n  Fail ures  are all s u bjects w h o  meet  o ne  of t he  
f oll o wi n g cate g ories: 
•  Di d n ot meet  S S  i ncl usi o n or met S S  e xcl usi o n 
•  Q ualifie d ref use d 
•  Recei ve d  We b  A p p  li n k b ut di d n ot c o m plete 
t he T A S S assess me nt 
•  Recei ve d  We b  A p p  li n k a n d recei ve d a “ D o N ot  Use”  
o utc o me  
•  Recei ve d We b A p p li n k a n d recei ve d a n  “ As k a D oct or” 
o utc o me a n d   di d  n ot g o  bac k  i nt o  t he We b  A p p   a n d 
i n dicate a d oct or sai d it was o ka y t o pr ocee d  
•  Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  
o utc o me or a n “ As k a D oct or” o utc o me a n d i n dicate d 
a d oct or sai d it was o ka y t o pr ocee d b ut ne ver create d 
a We b A p p acc o u nt 
•  Recei ve d We b A p p li n k, recei ve d a n “ O K t o Use” 
o utc o me or a n “ As k a D oct or” o utc o me a n d i n dicate d a 
d oct or sai d it was o ka y t o pr ocee d, create d a We b  A p p  
acc o u nt b ut  di d n ot ma ke  a n i nitial p urc hase of st u d y 
dr u g 
•  Recei ve d  We b  A p p  li n k, recei ve d a n “ O K t o Use”  
o utc o me or a n “ As k a D oct or” o utc o me a n d i n dicate d 
a d oct or sai d it was o ka y t o pr ocee d, create d  a We b  
A p p  acc o u nt, ma de a n i nitial p urc hase of st u d y dr u g 
b ut di d n ot sc he d ule t heir first visit 
•  Recei ve d We b A p p li n k, recei ve d a n “ O K t o Use”  
o utc o me or a n “ As k a D oct or” o utc o me a n d i n dicate d 
a d oct or sai d it was o ka y t o pr ocee d, sc he d ule d t heir 
first visit b ut di d n ot si g n I C F (eit her di d n ot s h o w f or 
t heir first visit  or s h o we d b ut deci de d  n ot t o si g n I C F) 
S S  P o p ulati o n  
Partici pa nts  w h o si g n  t he I C F. 

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A U S Scree n  Fail ures  
S S  p o p ulati o n  partici pa nts  w h o meet  A U S  e xcl usi o n criteria. 
A U S  I nte nt t o Treat  (I T T) 
P o p ulati o n  
S S  p o p ulati o n  partici pa nts  w h o  meet  all eli gi bilit y f or A U S 
a n d ha ve i n vesti gati o nal pr o d uct (I P) deli vere d t o t heir 
a d dress. 
Per Pr ot oc ol P o p ulati o n  
Partici pa nts i n t he A U S  I T T p o p ulati o n  w h o  c o m plete  
Virt ual  Visit  2 or ha ve s ufficie nt me dical a n d me dicati o n 
hist or y i nf or mati o n a n d, w he n necessar y, a verifie d L D L- C 
val ue c ollecte d pri or t o st o p pi n g t he st u d y t o deter mi ne t he 
fi nal use o utc o me. 
Safet y  
All partici pa nts i n t he A U S I T T w h o  ta kes at least o ne  d ose  
of I P as deter mi ne d b y ret ur ni n g fe wer pills t ha n dis pe nse d, 
i ncl u di n g t h ose w h o d o n ot ret ur n a n y b ottles f or pill 
c o u nti n g. As s uc h, a n y partici pa nts w h o ret ur n all pills 
deli vere d t o t he m are e xcl u de d.  
 
9. 4  
St atistic al  A n al yses  
T he  Statistical  A nal ysis Pla n ( S A P)  will be  fi nalize d pri or t o data base  l oc k ( D B L) a n d will 
i ncl u de a m ore  tec h nical a n d detaile d  descri pti o n  of t he statistical a nal yses descri be d  i n t his 
secti o n. T his secti o n is a s u m mar y of t he pla n ne d statistical a nal yses of t he m ost i m p orta nt 
e n d p oi nts i ncl u di n g pri mar y a n d ke y sec o n dar y e n d p oi nts. 
9. 4. 1  
Ge ner al  C o nsi der ati o ns  
9. 4. 1. 1  
S u b gr o u p  A n al yses  
Res ults f or all e n d p oi nts will be c o n d ucte d b y literac y gr o u p (li mite d, n or mal) as assesse d b y 
t he R E A L M  test as well as  b y se x at birt h, race, a n d a ge  gr o u p (less t ha n 5 0 years ol d, 5 0 – 6 5 
years  ol d, > 6 5 years  ol d)  gat here d  fr o m t he C M O G  cli nicia n res p o nses i n t he Tar gete d  Me dical 
a n d Me dicati o n Hist or y F or m at Visit 1. Res ults will als o be assesse d relati ve t o Or der 
Prefere nce ( base d o n t he  partici pa nt’s st u d y dr u g or der q ua ntit y, 4 5- or 9 0- da y s u p pl y) w hic h 
will be o btai ne d fr o m t he partici pa nt or der hist or y.  
9. 4. 1. 2  
We b A p p  Rec or ds  
W he ne ver t he  s u bject/ partici pa nt uses  t he We b  A p p, a rec or d of t hat i nteracti o n al o n g wit h  t he 
res p o nses t o t he q uesti o ns are create d. T here is t he p ote ntial f or m ulti ple rec or ds fr o m a 
s u bject/ partici pa nt si nce partici pa nts c o ul d e nter t he We b A p p a n d t he n e xit beca use t he y d o 
n ot ha ve t he i nf or mati o n nee de d t o c o m pl ete t he assess me nt.   T he r ule f or a d dressi n g t he iss ue 
of m ulti ple We b A p p rec or ds is t o al wa ys use t he s u bject’s/ partici pa nt’s last c o m plete d rec or d 
wit h a n o utc o me res ult f or a nal ysis.  A si milar pr ocess will be use d f or t he C M O G rec or ds  
c o m plete d  at Visit  1 a n d Visit  2. If m ulti ple C M O G  assess me nts  are rec or de d, t he last rec or d 

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will be use d f or t he e val uati o n of t he e n d p oi nts. T he reas o n f or m ulti ple C M O G assess me nts 
will be rec or de d.  
9. 4. 1. 3  
Miti g ati o n  Pl a n  
A li mite d n u m ber of miti gati n g fact ors will be acce pta ble f or partici pa nts w h o ver balize a n 
u n dersta n di n g of t he la bel war ni n gs or pr o vi de i nf or mati o n t hat w o ul d n ot be c o nsi dere d a 
me dical  ris k. Miti gati n g  fact ors ma y  be i de ntifie d d uri n g t he tar gete d me dical  a n d me dicati o n 
hist or y a n d will be a p plie d  d uri n g t he c o di n g pr ocess f or deter mi ni n g c orrect vs i nc orrect 
T A S S a n d use.  
T he miti gati o n pr ocess will be perf or me d after all partici pa nts ha ve c o m plete d t he st u d y. 
C o di n g of partici pa nt res p o nses a n d a p plicati o n of a n y miti gati o ns will be d o ne b y a n 
i nde pe n de nt tea m (i.e., fire walle d) c o m prise d of cli nicia ns a n d be ha vi oral e x perts. T he 
cli nicia ns  i n v ol ve d i n c o di n g a n d miti gati o ns  are n ot e m pl o yees of Astra Ze neca  or  Cle vela n d 
Cli nic.  T he y are e m pl o yees of C o nce ntrics Researc h.  Cli nicia ns are se parate d i nt o t w o 
disti nct gr o u ps f or t he p ur p ose of t his st u d y.  T he first gr o u p are C M O G cli nicia ns w h o are 
res p o nsi ble f or i nter vie wi n g partici pa nts d uri n g t he virt ual visits i n or der t o o btai n t heir 
me dical a n d me dicati o n hist ories a n d c o m plete t he C M O G T A S S assess me nts.  T he sec o n d 
gr o u p of cli nicia ns  are fire walle d fr o m t he C M O G  a n d are strictl y i n v ol ve d i n t he c o di n g a n d 
miti gati o n pr ocess after t he C M O G has c o m plete d t heir tas ks.   I n ot her w or ds, t his sec o n d 
gr o u p will n ot be cli nicia ns o perati n g i n t he C M O G.   T w o trai ne d c o ders will i n de pe n de ntl y 
c o de t he res ults a n d t he n c o m pare t he m. I n t he e ve nt of a disa gree me nt, a 3r d part y 
a dj u dicat or (a differe nt trai ne d c o der) will c o de t he res ults t o deter mi ne t he fi nal c o di n g 
assess me nt.  T he 3 r d part y a dj u dicat or is a n e m pl o yee of C o nce ntrics Researc h. C o ders will 
a p pl y b ot h t he cli nicall y pre-a p pr o ve d a pri ori miti gati o ns a n d t he p ost -st u d y miti gati o ns. 
F oll o wi n g t he miti gati o n  c o di n g pr ocess  c o n d ucte d b y C o nce ntrics Researc h,  t he Cle vela n d 
Cli nic me dical tea m i n c o nj u ncti o n wit h  t he Astra Ze neca me dical tea m ( w he n re q ueste d b y 
Cle vela n d Cli nic) will re vie w a n d a p pr o ve t he f oll o wi n g miti gati o ns: 
•  
all p ost-st u d y miti gati o ns  rec o m me n de d b y t he fire walle d c o di n g a n d miti gati o n tea m, 
•  
all re mai ni n g i nc orrect o utc omes  t o c o nfir m t hat n o a d diti o nal p ost-st u d y miti gati o ns are 
a p plica ble a n d 
•  
a n y iss ue relate d t o t he a p plicati o n of  t he a pri ori  miti gati o ns  
 
T he Cle vela n d Cli nic a n d Astra Ze neca me dical tea ms will be bli n de d t o t he i m pact t hat p ost -
st u d y miti gati o ns will ha ve o n t he st u d y res ults.  
A p pr o ve d miti gati o ns  will  be e ntere d i nt o t he st u d y data base  b y t he fire walle d c o ders a n d data 
ma na ge me nt staff.  

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T he  miti gat i o ns t hat were  a p plie d t o t he sec o n d c o-pri mar y  e n d p oi nt will  be utilize d  w he n 
assessi n g t he a p plica ble sec o n dar y a n d 
 
•  
A Pri ori  miti gati o ns:  T hese  are a ntici pate d res p o nses t hat w o ul d be c o nsi dere d  c orrect, 
after a pri ori miti gati o ns, us uall y si nce  t here is n o  safet y ris k. See Ta ble  5 a n d Ta ble  6 f or 
list of a pri ori miti gati o ns.  
•  
P ost -st u d y miti gati o ns: W hile e ver y eff ort is ma de t o a ntici pate a n d d oc u me nt miti gati o ns 
a pri ori , t here is c o m m o nl y s o me i nf or mati o n t hat c o ul d c o me t o li g ht i n c o nte xt of 
re vie wi n g all t he data o btai ne d via t he We b A p p a n d t he Tar gete d Me dical a n d 
Me dicati o n Hist or y fr o m t he C M O G cli nicia n. T heref ore, a n a d diti o nal re vie w will be 
c o m plete d p ost- st u d y t o assess w het her a n y a d diti o nal res p o nses c o ul d be miti gate d base d 
o n t he fact t hat t he res p o nses are a reas o ne d a n d acce pta ble a ns wer t o t he q uesti o n a n d 
p ose n o me dical ris k.  
 
T a ble  5 
I niti al Self -Selecti o n  Miti g ati o ns  
L a bel  Refere nce  
R ati o n ale  f or Miti g ati o n  
Pre g na nc y alert: D o  n ot use if y o u are pre g na nt 
or breastfee di n g. If y o u bec o me pre g na nt, st o p 
ta ki n g a n d call y o ur d oct or. 
 
 
Partici pa nt e nters “ n o” i n t he We b A p p b ut 
lear ns at a later date  t hat t he y were  pre g na nt. 
Partici pa nt di d n ot k n o w t he y were 
pre g na nt at t he ti me t he y use d t he We b 
A p p.  Partici pa nts w h o de m o nstrate t he y 
ha d k n o wle d ge of a pre g na nc y are n ot 
miti gate d.  
C CI
C CI

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D o n ot use if y o u are ta ki n g: 
− 
a n y c h olester ol-l o weri n g a n d/ or 
tri gl yceri de l o weri n g prescri pti o n 
me dici ne  
− 
c ycl os p ori ne (a me dici ne f or y o ur 
i m m u ne s yste m) 
− 
warfari n/ C O U M A DI N ® (a bl o o d 
t hi n ner) 
 
As k a D oct or bef ore use if y o u are ta ki n g: 
c olc hici ne (a me dici ne t o treat g o ut) 
HI V/ AI D S or he patitis me dici nes (s uc h as 
l o pi na vir, rit o na vir or ataza na vir) 
 
 
Partici pa nt e nters “ n o” i n t he We b A p p.  
Partici pa nt was n ot o n a me dici ne at t he 
ti me t he y t o o k t he T A S S assess me nt b ut 
starte d a me dici ne s u bse q ue ntl y, or t he 
partici pa nt was prescri be d a me dici ne b ut 
ha d n o i nte nti o n of ta ki n g t he me dici ne. 
D o n ot use if y o u are ta ki n g c ycl os p ori ne (a 
me dici ne f or y o u r i m m u ne s yste m). 
 
T he partici pa nt e nters “ n o” i nt o t he We b A p p.  
I n t he i nsta nce w here t he partici pa nt d oes 
n ot realize t hat a n e ye dr o p me dici ne t he y 
are usi n g has c ycl os p ori ne, t he y ma y e nter 
“ n o” i nt o t he We b A p p. A “ n o” res p o nse 
will be miti gate d t o c or rect beca use t he l o w 
c o nce ntrati o n a n d ver y l o w s yste mic 
a bs or pti o n of c ycl os p ori ne fr o m a n e ye dr o p 
f or m ulati o n will n ot si g nifica ntl y i m pact 
r os u vastati n e x p os ure, a n d t heref ore n ot 
p ose a ris k t o t he partici pa nt. 
As k a d oct or bef ore use if y o u ta ke: 
− 
c olc hici ne (a me dici ne t o treat g o ut) 
Partici pa nt a ns wers ‘ yes’ i n T A S S t o ta ki n g 
c olc hici ne b ut C M O G Cli nicia n deter mi nes 
t he y are n ot c urre ntl y ta ki n g b ut ha d ta ke n 
wit hi n 7 da ys of c o m pleti n g t he T A S S. 
Male 2 0 - 7 5 – Ta ke 1 ta blet e ver y da y  
Fe male  5 0-7 5 – Ta ke 1 ta blet e ver y da y  
 
 
Partici pa nt e nters a n a ge wit hi n 1 2 m o nt hs of 
t heir c orrect a ge. 
A Partici pa nt w h o e nters a n a ge wit hi n 1 2  
m o nt hs of t heir c orrect a ge will be 
miti gate d t o a c orrect res p o nse si nce t he 
be nefit ris k pr ofile of r os u vastati n will n ot 
be i m pacte d. 

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We b A p p  
R ati o n ale  f or Miti g ati o n  
Are y o u c urre ntl y ta ki n g a prescri pti o n me dici ne 
f or hi g h bl o o d press ure (als o k n o w n as 
“ h y perte nsi o n”)? 
 
Partici pa nt e nters “ n o” i nt o t he We b A p p.  
Partici pa nt was n ot o n a B P me dici ne at t he 
ti me t he y t o o k t he T A S S assess me nt b ut 
starte d a B P me dici ne s u bse q ue ntl y, or t he 
partici pa nt was prescri be d a B P me dici ne 
b ut ha d n o i nte nti o n of ta ki n g t he me dici ne.  
D o y o u s m o ke ci garettes?  
 
Partici pa nt e nters “ yes” i nt o t he We b A p p.  
Pa rtici pa nt sa ys “ yes” i n t he We b A p p t o 
s m o ki n g ci garettes, b ut C M O G Cli nicia n 
deter mi nes t hat partici pa nt o nl y s m o kes e-
ci garettes. 
 
T a ble  6 
Use Peri o d  Miti g ati o ns  
L a bel  Refere nce  
R ati o n ale  f or Miti g ati o n  
Pre g na nc y alert: D o n ot use if y o u are pre g na nt 
or breastfee di n g. If y o u bec o me pre g na nt, st o p 
ta ki n g a n d call y o ur d oct or. 
 
 
Partici pa nt bec o mes pre g na nt d uri n g t he st u d y 
b ut d oes n ot st o p ta ki n g t he dr u g a n d/ or d oes n ot 
call d oct or. 
Partici pa nt di d n ot k n o w t he y were 
pre g na nt w hile usi n g t he pr o d uct. 
Pre g na nc y alert: D o n ot use if y o u are pre g na nt 
or breastfee di n g. If y o u bec o me pre g na nt, st o p 
ta ki n g a n d call y o ur d oct or. 
 
 
Partici pa nt e nters “ n o” i n t he We b A p p b ut 
lear ns d uri n g t he fi nal visit t hat t he y were 
pre g na nt. 
Par tici pa nt di d n ot k n o w t he y were 
pre g na nt at t he ti me t he y use d t he We b 
A p p. 

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D o n ot use if y o u ha d a heart attac k, str o ke, 
peri p heral arter y disease ( P A D) or a n o perati o n 
or pr oce d ure o n y o ur heart. 
 
 
Partici pa nt e nters “ yes” i n t he We b A p p.  
W hile t he part ici pa nt belie ves, base d o n 
t heir hist or y, t hat t he y ha d o ne of t hese 
e ve nts, t he C M O G p h ysicia n deter mi nes 
t hat it was n ot a tr ue e ve nt. T he “ yes” 
res p o nse will be miti gate d t o c orrect 
beca use t he partici pa nt belie ve d t he y were 
gi vi n g a c orrect res p o nse a n d t heir res p o nse 
was a c o nser vati ve res p o nse, w hic h res ults 
i n t he m n ot q ualif yi n g f or Crest or O T C. I n 
t his case, n o me dical har m ca n c o me t o t he 
partici pa nt base d o n t his res p o nse.  
D o n ot use if y o u are ta ki n g: 
− 
a n y c h olester ol-l o weri n g a n d/ or 
tri gl yceri de l o weri n g prescri pti o n 
me dici ne  
− 
c ycl os p ori ne (a me dici ne f or y o ur 
i m m u ne 
− 
s yste m)  
− 
warfari n/ C O U M A DI N ® (a bl o o d 
t hi n ner) 
 
As k a D oct or bef ore use if y o u are ta ki n g: 
c olc hici ne (a me dici ne t o treat g o ut) 
HI V/ AI D S or he patitis me dici nes (s uc h as 
l o pi na vir, rit o na vir or ataza na vir) 
 
 
Partici pa nt e nters “ n o” i n t he We b A p p.  
Partici pa nt was n ot o n a me dici ne at t he 
ti me t he y t o o k t he T A S S assess me nt b ut 
starte d a me dici ne s u bse q ue ntl y, or t he 
partici pa nt was prescri be d a me dici ne b ut 
ha d n o i nte nti o n of ta ki n g t he me dici ne. 
D o n ot use if y o u are ta ki n g c ycl os p ori ne (a 
me dici ne f or y o ur i m m u ne s yste m).  
 
T he partici pa nt e nters “ n o” i nt o t he We b A p p.  
I n t he i nsta nce w here t he partici pa nt d oes 
n ot realize t hat a n e ye dr o p me dici ne t he y 
are usi n g has c ycl os p ori ne, t he y ma y e nter 
“ n o” i nt o t he We b A p p. A “ n o” res p o nse 
will be miti gate d t o c orrect beca use t he l o w 
c o nce ntrati o n a n d ver y l o w s yste mic 
a bs or pti o n of c ycl os p ori ne fr o m a n e ye dr o p 
f or m ulati o n will n ot si g nifica ntl y im pact 
r os u vastati n e x p os ure, a n d t heref ore n ot 
p ose a ris k t o t he partici pa nt. 

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St o p Use a n d As k a D oct or if y o u: 
get se vere a n d u ne x plai ne d m uscle pai n, 
te n der ness or wea k ness 
get s y m pt o ms of li ver pr o ble ms ( u p per bell y 
pai n, dar k uri ne, yell o wi n g of s ki n or w hites of 
e yes) 
W hile t he partici pa nt belie ves, base d o n 
t heir hist or y, t hat t he y ha d o ne of t hese 
e ve nts, t he C M O G p h ysicia n deter mi nes 
t hat it was n ot a tr ue e ve nt. T he “st o p use” 
will be miti gate d t o c orrect beca use t he 
partici pa nt belie ve d t he y wer e ta ki n g t he 
c orrect acti o n a n d it was a c o nser vati ve 
acti o n, w hic h res ults i n t he m n ot c o nti n ui n g 
t o ta ke Crest or O T C. I n t his case, n o 
me dical har m ca n c o me t o t he partici pa nt 
base d o n t his acti o n. 
Ot her  
R ati o n ale  f or Miti g ati o n  
L ost O p p ort u nit y  
C M O G Cli nicia n deter mi nes it was o k f or 
s o me o ne t o ta ke t he dr u g b ut base d o n 
res p o nses i n t he We b A p p, partici pa nt g ot a 
“ D o N ot Use” ( D N U) or “ As k a D oct or” 
( A A D). 
 
Partici pa nt deci des t o st o p ta ki n g st u d y 
me dicati o n a n d disc o nti n ues fr o m t he 
st u d y, b ut C M O G cli nicia n deter mi nes t hat 
t he y were “ O K t o Use.” 

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Missi n g L D L -C Retests  
− 
Gi ve n c o ns u mers ca n o nl y p urc hase n o n-
presc ri pti o n r os u vastati n t hr o u g h t he 
We b A p p, we ca n st o p s hi p pi n g 
me dicati o n t o i n di vi d uals w h o fail t o 
retest after a peri o d of ti me 
 
T h us, f or partici pa nts w h o q ualif y 
f or treat me nt (i.e., ha ve a n “ O K t o Use” 
o utc o me or a n “ As k a D oct or” o utc o me 
a n d i n dicates t he d oct or ga ve t he m 
per missi o n t o use t he dr u g) b ut fail t o 
o btai n t he necessar y verifie d retest(s) 
( w het her it is a n i nitial retest or a sec o n d 
retest i n t h ose wit h a n i na de q uate 
res p o nse), a n a pri ori miti gati o n all o wi n g 
t hese i n di vi d uals t o be miti gate d t o a 
“c orrect” res p o nse is a p pr o priate. T his 
miti gati o n ca n o nl y be a p plie d i n 
sit uati o ns w here t he C M O G’s o utc o me 
was “c o de d” as “ missi n g” beca use of a 
missi n g L D L - C val ue, a n d t he C M O G’s 
T A S S o utc o me w o ul d ha ve matc he d t he 
Partici pa nt O utc o me if n ot f or t he 
missi n g L D L -C retest.  
C M O G fi nal T A S S assess me nt is “ O K t o 
Use” or “ As k a D oct or”, b ut is c o de d as 
“ Missi n g” beca use t he partici pa nt faile d t o 
o btai n a verifie d L D L -C retest or a n S M T.  
C M O G fi nal T A S S assess me nt is “ O K t o 
Use” b ut c o de d as “ Missi n g” beca use t he 
partici pa nt faile d t o retest a n d t he S M T was 
a n I na de q uate Res p o nse, o r t he partici pa nt 
self-teste d wit h a verifie d i na de q uate 
res p o nse res ult t hat was use d f or t heir 
Visit  2 reassess me nt.  
Partici pa nt e nters a n i nitial I na de q uate 
Res p o nse L D L -C retest i nt o t he We b A p p 
( verifie d or u n verifie d), has a n “ O K t o 
Use” o utc o me or “ As k a D oct or” o utc o me, 
i n dicates t he d oct or ga ve t he m per missi o n 
t o use t he dr u g a n d ma kes a p urc hase. 
C M O G fi nal T A S S assess me nt is c o de d as 
“ Missi n g” beca use o nl y o ne or n o verifie d 
L D L -C retest val ue was a vaila ble f or use, 
b ut ot her wise w o ul d ha ve matc h e d t he 
partici pa nt o utc o me.  
 
9. 4. 1. 4  
M a n a gi n g V ari a bilit y  of L a b or at or y, Bl o o d Press ure a n d W aist 
Circ u mfere nce  D at a  fr o m Differe nt  S o urces  
I n t his st u d y, s u bjects are re q uire d t o ha ve B P a n d c h olester ol testi n g perf or me d at a l ocal 
testi n g site if t he y ca n n ot pr o vi de verificati o n f or t he data t he y e ntere d i nt o t he T A S S t o ol. If 
a s u bject/ partici pa nt is u na ble t o get t o  o ne of t he  l ocal testi n g sites, t he st u d y staff ca n direct 
t he m t o or der a h o me test kit. If a s u bject has a n F D A a p pr o ve d B P de vice at h o me, t he y will 
be all o we d t o use t heir de vice.  Ge neral i nstr ucti o ns o n tec h ni q ues t o meas ure B P will be 
pr o vi de d. See Secti o n  8  f or f urt her details. Si nce t he data o btai ne d fr o m t he l ocal testi n g site 
or t he h o me test kit i n al m ost all i nsta nces will n ot matc h e xactl y t he data e ntere d b y t he 
s u bject/ partici pa nt i n t he T A S S  t o ol, r ules are esta blis he d t o deter mi ne w het her t he data 
e ntere d b y t he s u bject/ partici pa nt s h o ul d be c o nsi dere d a tr ue reflecti o n of t heir la b orat or y a n d 
B P  data.   N u mer o us fact ors ca n c o ntri b ute t o varia bilit y  i n t hese meas ure me nts o ver ti me. 
E xa m ples i ncl u de c ha n ges i n diet, t he ti me of da y t he sa m ple was ta ke n, w het her t he  
i n di vi d ual was  fasti n g or n o n-fasti n g, t he la b orat or y or pers o n perf or mi n g  t he a nal ysis, a n d i n 
t he case of B P, w hite c oat i ncreases i n press ure or circa dia n varia bilit y. Beca use of t hese 
C CI

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fact ors, setti n g a le vel of varia bilit y t hat w o ul d be  dee me d acce pta ble f or eac h la b test or f or a 
B P meas ure me nt is e xtre mel y diffic ult.  
Base d o n t he fi n di n gs fr o m t he pi v otal Self- Selecti o n St u d y, t he vast maj orit y of partici pa nts 
e ntere d la b orat or y a n d B P  data t hat were  a n a p pr o priate re prese ntati o n of t heir  tr ue data. Of 
t he 5 0 0 partici pa nts i n t he per pr ot oc ol p o p ulati o n, 7 of t he 1 7 i nc orrect reject ors a n d 1 of t he 
3 i nc orrect select ors were d ue t o la b or B P data err ors. I n all ot her sit uati o ns, t he la b orat or y 
a n d B P data di d n ot i m pact t he pri mar y T A S S o utc o me assess me nt. Beca use partici pa nts i n 
t he A U S will nee d a n “ O K t o Use” o utc o me ( or per missi o n fr o m a d oct or if t he y get a n “ As k 
a D oct or” o utc o me) t o pr ocee d i nt o t he use peri o d, t he y will nee d t o e nter precise la b orat or y 
a n d B P data t o meet t he treat me nt eli gi bilit y re q uire me nts. As de m o nstrate d i n t he Self-
Selecti o n St u d y, e nteri n g fa ke n u m bers is hi g hl y li kel y t o res ult i n a “ N ot Ri g ht f or Y o u” (i.e., 
“ D o N ot  Use”) o utc o me, a n d if s u bjects tr y t o g uess n u m bers t o get access t o dr u g, t he y will 
get l oc ke d o ut of t he We b A p p after 3 faile d atte m pts a n d will ha ve t o wait f or at least o ne 
h o ur bef ore t he y ca n reta ke t he assess me nt.  
I n t his st u d y, varia bilit y criteria will o nl y be use d f or t he assess me nt of t he first c o-pri mar y 
e n d p oi nt a n d will o nl y be a p plie d w he n t he partici pa nt a n d C M O G cli nicia n T A S S o utc o mes 
at Visit 1 differ beca use of t hese val ues. I n ot her w or ds, if t he T A S S o utc o mes f or t he 
partici pa nt  a n d C M O G  cli nicia n a gree, t he la b orat or y a n d B P  val ues e ntere d b y t he partici pa nt 
will be c o nsi dere d acce pta ble.  Beca use partici pa nts m ust q ualif y f or treat me nt t o e nter t he 
st u d y, all of t he m, e xce pt y o u n g males, are re q uire d t o ha ve a 1 0 -yr A S C V D ris k sc ore wit hi n 
t he a p pr o priate ra n ge. Dia betic users are re q uire d t o ha ve a n A S C V D ris k sc ore of 0 % t o 
< 2 0 %, a n d n o n- dia betic users are re q uire d t o ha ve a n A S C V D ris k sc ore of 5 % t o < 2 0 %.  
Si nce T C, H D L a n d s yst olic B P are use d i n t he ris k sc ore calc ulati o n, t hese val ues will be 
c o nsi dere d acce pta ble if t he C M O G cli nicia n T A S S o utc o me is > 4 % f or n o n -dia betic users. 
T his c ha n ge fr o m t he criteria a p plie d i n t he Self -Selecti o n st u d y is beca use all partici pa nts 
wit h a ris k > 5 % are p ote ntial ca n di dates f or stati n t hera p y. T he o nl y partici pa nts w h o s h o ul d 
n ot be treate d are t h ose f or w h o m t he C M O G cli nicia ns’ assess me nts i n dicate t he y are l o w 
ris k. Dia betics are e xcl u de d fr o m t his varia bilit y assess me nt as 0 % t o < 5 % A S C V D ris k sc ore 
is acce pta ble. 
W hile t he n u mer o us fact ors descri be d earlier ca n c o ntri b ute t o varia bilit y i n la b orat or y 
meas ure me nts,  esta blis hi n g  acce pta ble le vels of  varia bilit y  t hat ta ke i nt o acc o u nt b ot h bi ol o gic 
a n d a nal ytic s o urces of varia bilit y w o ul d  re q uire setti n g ar bitrar y a n d, i n s o me i nsta nces, (e. g., 
T G le vels) ver y lar ge acce pta bilit y criteria.  T heref ore, f or t his st u d y, t he acce pta ble le vel of 
la b orat or y varia bilit y is base d o n T he Nati o nal C h olester ol E d ucati o n Pr o gra m ( N C E P) 
a nal ytical perf or ma nce g oals as s h o w n bel o w  (C o nt ois et al 2 0 1 1 ).  
T otal C h olester ol:   
< 9 %  
Tri gl yceri des:   
< 1 5 %  

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L D L -C:  
< 1 2 %  
H D L -C:  
< 1 3 %  
N o  varia bilit y  criteria will  be a p plie d t o t he L D L - C retest val ue  f or Visit  2 t o acc o u nt f or 
differe nces i n partici pa nt a n d C M O G T A S S o utc o mes d ue t o t he retest L D L- C.  
T he acce pta ble varia bilit y f or B P meas ure me nts is m ore diffic ult t o ascertai n  base d o n a 
re vie w of t he literat ure. I m p orta nt fact ors t hat c o ul d i m pact varia bilit y i ncl u de t he ti mi n g of 
t he B P  meas ure me nt  beca use  of t he circa dia n varia bilit y  i n B P,  t he use of a differe nt de vice  
f or t he partici pa nt’s  i n p utte d B P  vers us t he testi n g site i n p utte d B P,  o perat or varia bilit y w he n 
usi n g ma n ual de vices, a n d w hite c oat B P effects.   I n li g ht of t hese fact ors a n d ta ki n g i nt o 
acc o u nt t hat a  n or mal circa dia n c ha n ge  is B P  o ver t he c o urse of 2 4 h o urs c o ul d be 1 0 %  t o 
2 0 %, we set t he acce pta ble varia bilit y f or s yst olic a n d diast olic B P at 1 5 %.  
W he n  a p pl yi n g t he varia bilit y  criteria, t he acce pta ble  le vel of varia bilit y  will  be a p plie d t o t he 
C M O G la b orat or y or B P res ult t o deter mi ne if it o verla p pe d wit h t he partici pa nt’s data. F urt her 
details o n t he pr ocess f or a p pl yi n g t he varia bilit y criteria will be f o u n d i n t he S A P. 
T he  acce pta ble  le vel of varia bilit y  criteria f or t he la b orat or y a n d B P  data will  be use d t o 
ma na ge t he f oll o wi n g sit uati o ns:  
1  
T he differe nce bet wee n t he la b orat or y a n d/ or B P data e ntere d b y t he partici pa nt a n d t he 
o ne o btai ne d b y t he testi n g site was s mall b ut was e n o u g h t o c ha n ge t he assi g n me nt  of a 
Ris k  E n ha nci n g Fact or  ( R E F) t hat was  use d  t o deter mi ne  eli gi bilit y f or treat me nt. T his 
will o nl y  a p pl y f or partici pa nts wit h a 1 0- yr A S C V D ris k sc ore of 5 % t o < 7. 5 % si nce 
t h ose at hi g her ris k d o n ot re q uire a R E F. 
2  
T he differe nce bet wee n t he la b orat or y a n d/ or B P data e ntere d b y t he partici pa nt a n d t he 
o ne o btai ne d b y t he testi n g site was  s mall b ut was  e n o u g h t o ta ke t he val ue  o utsi de t he 
treat me nt ra n ge. 
 
W hile t he We b A p p pr o vi des i nstr ucti o ns t o i n di vi d uals re gar di n g h o w t o perf or m a waist 
circ u mfere nce meas ure me nt, s o me varia bilit y is li kel y t o be o bser ve d bet wee n t he 
meas ure me nt ta ke n b y t he partici pa nt a n d t he meas ure me nt ta ke n d uri n g t he Virt ual Visit 1. 
Pell o we, et. al. re p orte d t hat waist circ u mfere nce meas ure me nts ca n var y si g nifica nt l y 
de pe n di n g o n w he n d uri n g t he res pirat or y c ycle t he meas ure me nt is ta ke n or t hr o u g h 
v oliti o nal alterati o n i n a b d o mi nal diste nsi o n. A d diti o nall y, t he y o bser ve d si g nifica nt 
alterati o ns i n waist circ u mfere nce u p t o 6. 5 % w he n meas ure me nts are ta ke n d uri n g differe nt 
ti mes of t he da y (Pell o we et al 2 0 1 0 ). T he iss ue of varia bilit y i n waist circ u mfere nce 
meas ure me nts has als o bee n re p orte d b y ot hers (Ma s o n et al 2 0 1 8). F or t he p ur p ose of t his 
st u d y, a waist circ u mfere nce meas ure me nt e ntere d i nt o t he T A S S t o ol b y t he partici pa nt will 
be c o nsi dere d verifie d if b ot h t he partici pa nt a n d C M O G meas ure me nts meet, or d o n ot meet, 

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t he criteri o n f or t he meta b olic s y n dr o me (i.e., waist circ u mfere nce > 3 5 i nc hes f or fe males a n d 
> 4 0 i nc hes f or males), or if waist circ u mfere nce meas ure me nts are dis parate f or meeti n g t he 
meta b olic s y n dr o me criteri o n, t he partici pa nt val ue is wit hi n 6. 5 % of t he C M O G val ue.  
9. 4. 2  
St u d y  E n d p oi nts  
9. 4. 2. 1  
Pri m ar y  E n d p oi nt(s)  
T he first c o -pri mar y a nal ysis will e val uate t he perce nta ge of partici pa nts w h o ac hie ve d a n 
O verall C orrect I nitial T A S S O utc o me at t he i nitial self -selecti o n. T he Se lf-Selecti o n ( S S) 
p o p ulati o n will be  t he pri mar y p o p ulati o n use d f or t his a nal ysis; h o we ver, a sec o n d e val uati o n 
usi n g t he A U S I T T p o p ulati o n a n d P P p o p ulati o n will als o be perf or me d. T he sec o n d c o -
pri mar y a nal ysis will e val uate  t he perce nta ge  of partici pa nts  w h o  ac hie ve d a n O verall  C orrect  
Fi nal  Use  O utc o me at t he fi nal use assess me nt.   T he Per Pr ot oc ol ( P P) p o p ulati o n will be t he 
pri mar y p o p ulati o n use d f or t his e n d p oi nt a nal ysis (see Secti o n  9. 3  f or defi niti o ns of a nal ysis 
p o p ulati o ns).   F or t hese e val uati o ns, t he o utc o mes o btai ne d b y t he partici pa nt will be 
c o m pare d t o t he o utc o mes o btai ne d b y t he C M O G cli nicia n f oll o wi n g verificati o n of t he 
partici pa nt’s me dical a n d la b orat or y data. T he t hir d c o - pri mar y a nal ysis will e val uate perce nt 
c ha n ge fr o m baseli ne ( P C F B) i n verifie d L D L- C val ues t o Visit 2 i n partici pa nts i n t he A U S 
I T T p o p ulati o n re gar dless of t heir fi nal use o utc o me. 
T he  t hree c o-pri mar y  e n d p oi nts are e val uate d  as f oll o ws: 
1  
Perce nta ge of partici pa nts wit h a n O verall C orrect  (c orrect + miti gate d) I nitial T A S S 
O utc o me at t he i nitial self -selecti o n, defi ne d as t he n u m ber of partici pa nts wit h a c orrect 
i niti al T A S S o utc o me di vi de d b y t he n u m ber of partici pa nts i n t he a nal ysis p o p ulati o n  
( T hres h ol d:  8 5 % L B).  T h ose partici pa nts wit h  a missi n g  C M O G  cli nicia n i nitial T A S S 
o utc o me will be c o u nte d as I nc orrect f or t he e n d p oi nt. T his will be calc ulate d as f oll o ws: 
O verall  C orrect I nitial T A S S O utc o me ( %) =                      
C S +  C A A D +  M R
A P +  M R
P S  
#  of  partici pa nts  i n t he a nal ysis 
p o p ulati o n  
 
A 9 5 % c o nfi de nce i nter val will  be c o m p ute d usi n g  e xact bi n o mial  met h o ds (i.e., Cl o p per- 
Pears o n) f or t he pr o p orti o n of eac h c orrect o utc o me a m o n g t he e ntire S S P o p ulati o n.  
Fi g ure 2  bel o w pr o vi des a matri x  of C orrect  a n d I nc orrect Select ors  or As k  a D oct or base d  o n 
t he partici pa nt a n d C M O G cli nicia n T A S S o utc o mes f or t he i nitial T A S S assess me nt.  

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Fi g ure  2 
T w o -b y -F o ur  T a ble  Ill ustr ati n g P ossi ble  Self -Selecti o n  O utc o mes  f or 
I niti al T A S S Assess me nt 
 
 
C M O G  Cli nici a n  Verifie d  I niti al T A S S  O utc o me  
 
 
O k t o Use  
A A D  
D o N ot Use  
Missi n g  
 
 
P artici p a nt 
I niti al T A S S  
O utc o me  
 
O k t o Use  
C orrect  
Selecti o n  
( CS  + M C S ) 
I nc orrect  
Selecti o n  
I nc orrect 
Selecti o n  
I nc orrect 
Missi n g  
 
A A D  
I nc orrect 
A A D  
C orrect A A D  
( CA A D  + M C A A D ) 
I nc orrect 
A A D  
I nc orrect 
Missi n g  
 
T he  pri mar y  a nal ysis f or t he O verall  C orrect  I nitial T A S S  O utc o me will  re p orte d as f oll o ws: 
 
A nal ysis  P o p ulati o n  
( N = X X X) 
N  
%  
9 5 %  CI  
O verall  C orrect  I nitial T A S S O utc o me  
X X  
X X %  
( L B %, U B %)  
C orrect  Select ors  
X X  
X X %  
( L B %, U B %)  
C orrect  A A D  
X X  
X X %  
( L B %, U B %)  
M R
a p 
X X  
X X %  
( L B %, U B %)  
M R
ps 
X X  
X X %  
( L B %, U B %)  
 
w here,  
•  
C orrect Select ors ( C S ) = O btai n a c orrect T A S S o utc o me t hat t he y q ualif y f or Crest or 
O T C  b y recei vi n g a n ‘ O K t o Use’ scree n i n t he T A S S (c o m pare d t o t he C M O G cli nicia n 
e val uati o n) 
•  
C orrect A A D  ( CA A D ) = O btai n a c orrect  T A S S  o utc o me t hat t he y m ust as k a d oct or bef ore 
q ualif yi n g f or Crest or O T C b y recei vi n g a n ‘ As k a D oct or’ scree n i n t he T A S S (c o m pare d 
t o t he C M O G cli nicia n e val uati o n) 
•  
M R
a p = Miti gate d  res ults a pri ori  
•  
M R
ps  = Miti gate d  res ults p ost-st u d y (s h o ul d t here be a n y p ost-st u d y miti gati o ns).  
 

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T he pri mar y a nal ysis of t he first c o -pri mar y e n d p oi nt will be base d o n a w orst case sce nari o 
missi n g data i m p utati o n w here all partici pa nts i n t he res pecti ve a nal ysis p o p ulati o n wit h a 
missi n g C M O G cli nicia n i nitial T A S S  o utc o me will be c o u nte d as I nc orrect f or t he e n d p oi nt. 
A n a d diti o nal sec o n dar y a nal ysis of t his e n d p oi nt will be c o n d ucte d base d o n t he A U S I T T 
p o p ulati o n. I n a d diti o n t o t he w orst case sce nari o a nal ysis f or t he first c o- pri mar y e n d p oi nt, 
se nsiti vit y a nal yses will be perf or me d o n t he partici pa nts i n t he S S p o p ulati o n wit h a n o n- 
missi n g i nitial T A S S o utc o me  f or t he C M O G  cli nicia n (i.e., c o m plete  case a nal ysis) a n d wit h 
missi n g O verall C orrect I nitial  T A S S O utc o me  data  i m p ute d usi n g best case i m p utati o n a n d a 
ti p pi n g p oi nt a nal ysis. F urt her details f or t h ose partici pa nts ( or C M O G cli nicia n) wit h missi n g 
i nitial T A S S o utc o mes a n d t he se nsiti vit y a nal yses will be descri be d i n t he st u d y S A P.  
2  
Perce nta ge of partici pa nts wit h a n O verall C orrect (c orrect + miti gate d) Fi nal Use 
O utc o me at t he fi nal use assess me nt, defi ne d as t he n u m ber of partici pa nts wit h a c orrect 
fi n al use o utc o me di vi de d b y t he n u m ber of partici pa nts i n t he a nal ysis p o p ulati o n wit h  a 
n o n- missi n g  fi nal use o utc o me f or b ot h t he partici pa nt a n d C M O G cli nicia n ( T hres h ol d: 
8 5 % L B). T his will be calc ulate d as f oll o ws:  
O verall C orrect Fi nal  Use  O utc o me ( %) = 
C S +  C A A D +  C R +  M R
A P +  M R
P S  
# of partici pa nts i n t he  a nal ysis p o p ulati o n 
wit h a  n o n-missi n g fi nal  use o utc o me f or 
b ot h  t he partici pa nt  a n d C M O G  cli nicia n 
 
A 9 5 % c o nfi de nce i nter val will  be c o m p ute d usi n g  e xact bi n o mial  met h o ds (i.e., Cl o p per- 
Pears o n) f or t he pr o p orti o n of eac h c orrect o utc o me a m o n g t he e ntire P P P o p ulati o n. 
Fi g ure 3  bel o w pr o vi des a matri x  of C orrect  a n d I nc orrect Select ors,  As k  a D oct or, or 
Reject ors base d o n t he partici pa nt a n d C M O G cli nicia n e val uati o ns f or t he fi nal use 
assess me nt. 

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Fi g ure  3 
T hree -b y -T hree  T a ble  Ill ustr ati n g P ossi ble  Self -Selecti o n  O utc o mes  f or 
Fi n al Use Assess me nt  
 
 
C M O G  Cli nici a n  Verifie d  Fi n al  Use  O utc o me  
 
 
O k t o Use  
A A D  
D o N ot Use  
 
 
 
 
P artici p a nt Fi n al 
Use O utc o me  
 
O k t o Use  
C orrect  
Selecti o n  
( Cs +M C s) 
I nc orrect 
Selecti o n  
I nc orrect 
Selecti o n  
 
A A D  
I nc orrect 
A A D  
C orrect A A D  
( CA A D + M C A A D ) 
I nc orrect 
A A D  
 
D o N ot Use  
I nc orrect 
Rejecti o n  
I nc orrect 
Rejecti o n  
C orrect  
Rejecti o n  
( CR + M C R ) 
 
Si nce partici pa nts are gi ve n a li mite d s u p pl y (i.e., 4 5 or 9 0 da y) of r os u vastati n wit h eac h 
or der, t he y are li kel y t o ha ve m ulti ple re or der assess me nts o ver t he d urati o n of t he trial. W hile 
t his will occ ur, t he critical re or der assess me nt f or t he sec o n d c o- pri mar y e n d p oi nt will al wa ys 
be t he last o ne ta ke n b y t he partici pa nt beca use it re prese nts t heir fi nal use o utc o me. F or t he 
p ur p oses of t his  st u d y, a partici pa nt’s  fi n al use assess me nt will  refer t o t he last re or der 
assess me nt t he y recei ve d d uri n g t he st u d y, i ncl u di n g t he fi nal use assess me nt ta ke n at Virt ual 
Visit 2.  T he fi nal use assess me nts will be deter mi ne d base d o n t he f oll o wi n g criteria.  
1  
F or t h ose partici pa nts  w h o  get a n “ O K t o Use”  o utc o me wit h  eac h re or der, t heir fi nal use 
assess me nt  will  be perf or me d  at t he e n d of t he 6- m o nt h use peri o d  d uri n g Virt ual Visit 2.  
2  
F or partici pa nts  w h o  get a “ D o N ot  Use”  o utc o me as t heir last re or der assess me nt  pri or t o 
t he e n d of t he 6-m o nt h use peri o d, t heir Virt ual  Visit 2 will occ ur earlier.  T he last re or der 
assess me nt w hic h res ulte d i n t he “ D o N ot Use” o utc o me will be use d as t heir fi nal use 
assess me nt. 
(a) N ote t hat a “ D o N ot Use” o utc o me occ urs w he n e ver a partici pa nt meets D F L or 
L D L - C l o weri n g criteria t hat w o ul d re q uire t he partici pa nt  t o st o p treat me nt. T his 
mea ns t hat a partici pa nt w h o meets a St o p Use or D o N ot Use criteri o n fr o m t he D F L 
will recei ve t he sa me “ D o N ot Use” o utc o me a n d be e val uate d as “ D o N ot Use” f or 
t he p ur p ose of t he sec o n d c o- pri mar y e n d p oi nt.  F or t he p ur p ose of e val uati o n of t he 
sec o n dar y e n d p oi nts, t he reas o ns f or t he “ D o N ot Use” o utc o mes will be assesse d i n 
or der t o place t he m i n t he a p pr o priate cate g or y f or e val uat i o n. I n ot her w or ds, 
partici pa nts w h o recei ve d a “ D o N ot Use” o utc o me d ue t o a St o p Use criteri o n i n t he 
D F L will be assi g ne d t o t he St o p Use cate g or y f or e val uati o n. 
3  
F or partici pa nts w h o get a n “ As k a D oct or” o utc o me d uri n g t he use peri o d, t he y will be 
gi ve n u ntil t he e n d of t he 6- m o nt h use peri o d t o s pea k t o a d oct or. Si nce partici pa nts 

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ca n n ot re or der dr u g u ntil t he y s pea k t o t he d oct or, t he ris k of c o nti n ui n g t he m i n t he st u d y 
is l o w. I m p orta ntl y, all o wi n g t he m t o c o nti n ue f or t he f ull 6 m o nt hs gi ves us t he 
o p p ort u nit y t o assess w het her t he y will c o ntact a d oct or at s o me p oi nt. 
(a) If a d oct or gi ves t he m per missi o n t o c o nti n ue t hera p y, t he y will ta ke t he re or der 
assess me nt a n d i n dicate  t hat t he y ha d per missi o n t o c o nti n ue t hera p y. T he y will  be 
a ble t o re or der me dicati o n  a n d c o nti n ue i n t he st u d y. T heir  fi nal use assess me nt will 
be perf or me d  at t he e n d of t he 6- m o nt h use peri o d d uri n g t heir Virt ual Visit 2.  
( b) If t he y d o n ot  ta ke a n ot her re or der assess me nt, t he y  will  be see n at t he e n d of t he 
6- m o nt h use peri o d a n d t heir “ As k a D oct or” assess me nt will be use d as t heir T A S S 
fi nal use assess me nt. 
4  
F or  partici pa nts  w h o  disc o nti n ue fr o m st u d y i nter ve nti o n pri or t o st u d y c o m pleti o n a n d 
t heir last T A S S assess me nt was eit her “ O k t o Use” or “ As k a D oct or” a n d i n dicate d t he 
d oct or ga ve t he m per missi o n t o c o nti n ue treat me nt, t he st u d y staff will atte m pt t o 
c o m plete t he Virt ual Visit 2 pr oce d ures i n or der t o  ha ve a fi nal use assess me nt f or t he 
partici pa nt a n d t he C M O G cli nicia n.  If t he partici pa nt is u n willi n g t o pr o vide s ufficie nt 
me dical a n d me dicati o n hist or y f or t he C M O G t o ma ke a fi nal use deter mi nati o n, t he 
C M O G cli nicia n e val uati o n will be c o nsi dere d missi n g, a n d t he partici pa nt dee me d a 
wit h dra wal. T he i m pact of t he missi n g data will be assesse d i n t he se nsiti vi t y a nal ysis. 
See t he Statistical A nal ysis  Pla n  f or f urt her detail.  All  fi nal use  o utc o mes o btai ne d b y t he 
partici pa nt  will be c o m pare d t o t he use o utc o mes o btai ne d b y t he C M O G cli nicia n 
f oll o wi n g verificati o n of t he partici pa nt’s me dical a n d me dicati o n hist or y i nter vie w at 
Virt ual Visit 2.  
 
T he  pri mar y a nal ysis  f or t he O verall  C orrect  Fi nal  Use  O utc o me  will  be re p orte d as f oll o ws: 
 
A nal ysis  P o p ulati o n  
( N = X X X) 
n  
%  
9 5 %  CI  
O verall  C orrect  Fi nal  Use O utc o me  
X X  
X X %  
( L B %, U B %)  
C orrect  Select ors  
X X  
X X %  
( L B %, U B %)  
C orrect  A A D  
X X  
X X %  
( L B %, U B %)  
C orrect  Reject ors  
X X  
X X %  
( L B %, U B %)  
M R
a p 
X X  
X X %  
( L B %, U B %)  
M R
ps  
X X  
X X %  
( L B %, U B %)  

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w here,  
•  
C orrect Select ors  ( CS ) = O btai n  a c orrect o utc o me  t hat t he y q ualif y f or Crest or O T C 
(c o m pare d t o t he C M O G cli nicia n e val uati o n) 
•  
C orrect A A D  ( CA A D ) = O btai n a c orrect o utc o me  t hat t he y m ust as k a d oct or bef ore 
q ualif yi n g f or Crest or O T C (c o m pare d t o t he C M O G cli nicia n e val uati o n)  
•  
C orrect  Reject ors  ( CR ) = O btai n a c orrect  o utc o me t hat t he y d o  n ot q ualif y f or Crest or 
O T C (c o m pare d t o t he C M O G cli nicia n e val uati o n) 
•  
M R
a p = Miti gate d  res ults a pri ori 
•  
M R
ps  = Miti gate d  res ults p ost-st u d y (s h o ul d t here be a n y p ost-st u d y miti gati o ns). 
 
A se nsiti vit y a nal ysis f or t h ose partici pa nts  wit h missi n g data  f or t he sec o n d c o-pri mar y 
e n d p oi nt (i.e., t h ose partici pa nts i n t he A U S I T T p o p ulati o n b ut n ot t he P P p o p ulati o n) will be 
c o n d ucte d. T he missi n g data i m p utati o n met h o ds f or t he O verall C orrect Fi nal Use O utc o me 
will i ncl u de best case a n d w orst case i m p utati o n a n d a ti p pi n g p oi nt a nal ysis. F urt her details 
f or t h ose partici pa nts ( or C M O G cli nicia n) wit h missi n g fi nal use o utc o mes a n d t he se nsiti vit y 
a nal yses will be descri be d i n t he st u d y S A P. 
3  
T he  P C F B  i n verifie d  L D L - C val ues f or partici pa nts re gar dless of fi nal  use  o utc o me at 
Visit 2. T his e n d p oi nt is calc ulate d as f oll o ws:  
 
P C F B  =  
1 0 0 *( Verifie d  L D L -C  val ue  at Visit 2  –  Verifie d  L D L -C  val ue  at 
Baseli ne)  
 
Verifie d  L D L -C  val ue  at Baseli ne  
 
w here  t he verifie d L D L - C val ue at i nitial selecti o n will ser ve as Baseli ne. Ne gati ve 
val ues i n P C F B re prese nt a decrease i n L D L -C.  
T he P C F B f or verifie d L D L - C val ues will be s u m marize d b y s u b gr o u p a n d o verall usi n g 
descri pti ve statistics ( n, mea n, sta n dar d de viati o n, me dia n, mi ni m u m, ma xi m u m, a n d 
Q uartiles 1 a n d 3 [ Q 1 a n d Q 3]) f or t h ose partici pa nts i n t he A U S I T T p o p ulati o n. T he tar get 
t hres h ol d f or t his e n d p oi nt is t hat t he u p per b o u n d of t he 9 5 % c o nfi de nce  i nter val o n t he mea n 
P C F B  i n t he o verall a nal ysis nee ds t o be less t ha n -1 5 %, wit h a  P E  less t ha n or e q ual t o - 2 0 %. 
T here will be n o h y p ot hesis testi n g of t his e n d p oi nt i n t he s u b gr o u ps. 
T o test t he  r o b ust ness of t he t hir d c o -pri mar y  e n d p oi nt o n L D L- C efficac y, se veral se nsiti vit y 
a nal yses  will be perf or me d  t o deter mi ne t he effect t hat vari o us s o urces of L D L - C val ues ha ve 
o n t he L D L - C pri mar y  e n d p oi nt. Se nsiti vit y  a nal yses  of L D L - C efficac y will  be c o n d ucte d o n 
all partici pa nts wit h a verifie d baseli ne a n d retest L D L -C w h o are eli gi ble f or c o nti n u o us 
treat me nt, o n t he pri mar y L D L-C efficac y p o p ulati o n usi n g vari o us missi n g data i m p utati o n 
met h o ds f or missi n g verifie d o n -treat me nt L D L-C val ues,  o n all partici pa nts wit h a baseli ne 

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a n d retest L D L - C re gar dless of verificati o n stat us a n d Fi nal Use O utc o me, a n d fi nall y, o n all 
partici pa nts  w h o  e ntere d a baseli ne  a n d retest L D L - C i nt o t he We b  A p p  re gar dless of w het her 
t he test was verifie d. T hese se nsiti vit y a nal yses will be f urt her descri be d i n t he S A P. 

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9. 4. 2. 2  
Sec o n d ar y E n d p oi nt(s)  
C h olester ol  Retesti n g  
1  
Perce nta ge  of partici pa nts  w h o  are eli gi ble f or c o nti n u o us treat me nt, a n d ha ve a 
c h olester ol retest wit hi n 6  m o nt hs of starti n g me dicati o n t hat was verifie d  at Visit 2 will 
be calc ulate d as f oll o ws:  
 
 
Perce nta ge  =  
1 0 0 * ( N u m ber  of  partici pa nts  w h o  are eli gi ble f or c o nti n u o us 
treat me nt a n d ha d a c h olester ol  retest wit hi n  6 m o nt hs after 
starti n g me dicati o n t hat was verifie d at Visit 2) 
 
T otal n u m ber  of  partici pa nts  w h o  are eli gi ble  f or c o nti n u o us 
treat me nt 
 
T he n u m ber a n d perce nta ge of partici pa nts w h o are eli gi ble f or c o nti n u o us treat me nt a n d 
ha ve a c h olester ol retest wit hi n 6 m o nt hs of starti n g me dicati o n t hat was verifie d  at Visit 
2 will be s u m marize d b y s u b gr o u p a n d o verall. T h ose partici pa nts wit h a n u n verifie d 
c h olester ol  retest val ue at Visit 2, a n d t h us re q uire d st u d y ma n date d testi n g, will n ot be 
i ncl u de d i n t he n u merat or f or t his e n d p oi nt. T he t otal n u m ber of partici pa nts w h o  are 
eli gi ble f or c o nti n u o us treat me nt will  ser ve as t he de n o mi nat or f or t he perce nta ges. 
T he  tar get t hres h ol d f or t his e n d p oi nt is t hat t he o bser ve d  p oi nt esti mate nee ds  t o be at 
least 6 0 % o verall. 
C o m pli a nce  wit h St o p Use  W ar ni n g  
2  
Perce nta ge  of partici pa nts  w h o  c orrectl y self-i de ntif y as ha vi n g a “ St o p Use” war ni n g a n d 
st o p me dicati o n, calc ulate d as f oll o ws: 
 
Perce nta ge  = 
1 0 0 *  ( N u m ber of  partici pa nts  w h o  c orrectl y self-i de ntif y as 
ha vi n g a “ St o p Use” war ni n g  a n d st o p me dicati o n)  
T otal n u m ber  of  partici pa nts  w h o t he  C M O G  cli nicia n i de ntif y 
as ha vi n g a “ St o p Use” war ni n g  
 
T he n u m ber a n d perce nta ge of partici pa nts w h o c orrectl y self-i de ntif y as ha vi n g a “ St o p 
Use”  war ni n g a n d st o p me dicati o n  will  be s u m marize d b y s u b gr o u p a n d o verall. 
C o m pli a nce  wit h D o  N ot  Use  W ar ni n g  
3  
Perce nta ge  of partici pa nts  w h o  c orrectl y self-i de ntif y as ha vi n g a “ D o N ot  Use” war ni n g 
at t he fi nal use assess me nt, calc ulate d as f oll o ws:  
 
Perce nta ge  = 
1 0 0 *  ( N u m ber of  partici pa nts  w h o  c orrectl y self-i de ntif y as 
ha vi n g a “ D o N ot Use”  war ni n g at t he fi nal use assess me nt) 
T otal n u m ber  of  partici pa nts  w h o t he  C M O G  cli nicia n i de ntif y 
as ha vi n g a  “ D o N ot Use” war ni n g  
 

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T he  n u m ber a n d perce nta ge of partici pa nts w h o  c orrectl y self-i de ntif y as ha vi n g a “ D o 
N ot Use” war ni n g at fi nal use assess me nt will be s u m marize d b y s u b gr o u p a n d o verall.  
C o m pli a nce  wit h As k  a D oct or Bef ore  Use  W ar ni n g  
4  
Perce nta ge  of partici pa nts  w h o  c orrectl y self-i de ntif y as ha vi n g a n “ As k A D oct or Bef ore 
Use” war ni n g at t he fi nal use assess me nt calc ulate d as f oll o ws:  
 
 
Perce nta ge  = 
1 0 0 * ( N u m ber of partici pa nts w h o c orrectl y self -i de ntif y as 
ha vi n g a n “ As k a D oct or Bef ore  Use”  war ni n g at t he fi nal use 
assess me nt) 
 
T otal n u m ber  of  partici pa nts  w h o t he  C M O G  cli nicia n i de ntif y 
as ha vi n g a “ As k a D oct or Bef ore  Use”  war ni n g  
  
T he n u m ber a n d perce nta ge of partici pa nts w h o c orrectl y self- i de ntif y as ha vi n g a “ As k a 
D oct or Bef ore  Use”  war ni n g at t he fi nal use assess me nt  will  be  s u m marize d b y s u b gr o u p 
a n d o verall. 
C o m pli a nce  wit h  C o nti n u o us  D osi n g  
5  
Perce nta ge  of partici pa nts  wit h  o verall c o m plia nce  bet wee n  5 0 % a n d 1 2 0 % as deter mi ne d 
b y pill c o u nt. O verall C o m plia nce will be calc ulate d as f oll o ws:  
O verall C o m plia nce    = 
1 0 0 * ( T otal N u m ber of Pills  Ta ke n  ) 
I nte n de d D urati o n (i n da ys) of  Treat me nt  
 
w here  t he i nte n de d d urati o n of treat me nt is calc ulate d as  f oll o ws: 
I nte n de d D urati o n of 
Treat me nt =   
(I nte n de d Treat me nt St o p Date –  Date Partici pa nt 
Recei ve d First S u p pl y of St u d y Dr u g) + 1 Da y 
Beca use t here ma y be i nsta nces i n w hic h a partici pa nt c o nti n ues st u d y me dicati o n w he n  t he y 
s h o ul d n ot ha ve (i.e., partici pa nt e x perie nces  “ St o p Use,”, “ D o  N ot  Use,” or “ As k a D oct or” 
war ni n g) b ut d oes n ot st o p me dicati o n, i n or der t o pr o perl y assess c o m plia nce wit h c o nti n u o us 
d osi n g, t he i nte n de d d urati o n of treat me nt will be use d rat her t ha n t he act ual d urati o n of 
treat me nt. 
6  
Perce nta ge  of partici pa nts  wit h  l o n git u di nal c o m plia nce wit h  c o nti n u o us d osi n g acr oss 
eac h st u d y dr u g re or der s u p pl y peri o d as deter mi ne d usi n g e Diar y data, w here s u p pl y 
peri o d c o m plia nce  is calc ulate d f or eac h s u p pl y peri o d f or eac h partici pa nt as f oll o ws: 
S u p pl y  Peri o d 
C o m plia nce  = 
1 0 0 *  ( T otal N u m ber  of  Pills  Ta ke n  d uri n g  t he S u p pl y Peri o d  i 
base d  o n e Diar y) 
I nte n de d D urati o n  (i n da ys)  of  Treat me nt  i n S u p pl y  Peri o d  i 
 

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T he  L o n git u di nal C o m plia nce Rate,  or t he perce nta ge of partici pa nts  wit h  s u p pl y peri o d 
c o m plia nce bet wee n 5 0- 1 2 0 % acr oss eac h st u d y dr u g s u p pl y peri o d, is calc ulate d as 
f oll o ws: 
L o n git u di nal 
C o m plia nce  
Rate ( %)  = 
1 0 0 *( N u m ber of partici pa nts wit h 5 0 -1 2 0 % S u p pl y Peri o d 
C o m plia nce acr oss all s u p pl y peri o ds)  
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
_ T otal  n u m ber  of partici pa nts i n P P  p o p ulati o n  f or w h o m s u p pl y 
peri o d c o m plia nce was assesse d acr oss all s u p pl y peri o ds  
 
L o n git u di nal C o m plia nce Rate,  al o n g wit h  t he n u m ber of partici pa nts  wit h  5 0- 1 2 0 % 
s u p pl y peri o d  c o m plia nce  acr oss all s u p pl y peri o ds will  be s u m marize d b y  s u b gr o u p a n d 
o verall o n t he P P p o p ulati o n. 
7  
Perce nta ge of  partici pa nts w h o were persiste nt as deter mi ne d b y re or der data fr o m t he 
We b A p p will be calc ulate d as f oll o ws:  
 
Perce nta ge  =  
1 0 0 * ( N u m ber of partici pa nts w h o  were  persiste nt ) 
 
T otal n u m ber  of  partici pa nts  eli gi ble f or c o nti n u o us  treat me nt 
 
Persiste nce is defi ne d as partici pa nts eli gi ble f or c o nti n u o us treat me nt a n d deli vere d t he 
f ull 1 8 0 da ys or m ore of treat me nt. T he n u m ber a n d perce nta ge of partici pa nts w h o  were  
persiste nt  will  be s u m marize d b y s u b gr o u p a n d o verall o n t he P P p o p ulati o n a n d t he A U S 
I T T p o p ulati o n. 
9. 4. 2. 3  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI

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9. 4. 3  
S afet y  
All safet y a nal yses will be c o n d ucte d o n t he safet y p o p ulati o n (i.e., all partici pa nts i n t he A U S 
I T T P o p ulati o n e xce pt t h ose w h o ret ur n all pills deli vere d). 
A d verse  E ve nts  
A d verse e ve nts will be  c o de d usi n g t he m ost rece nt versi o n of t he Me dical Dicti o nar y  f or 
Re g ulat or y Acti vities ( Me d D R A) t hat will ha ve bee n release d f or e xec uti o n at 
Astra Ze neca/ desi g nee.  
Safet y  data  will  be prese nte d usi n g descri pti ve statistics  u nless ot her wise s pecifie d.  
A Es  will  be prese nte d  b y S O C  ( S yste m Or ga n  Class) a n d  P T  ( Preferre d Ter m) c o veri n g 
n u m ber a n d perce nta ge of partici pa nts re p orti n g at least o ne e ve nt a n d n u m ber of e ve nts 
w here a p pr o priate.  
A Es  will be  prese nte d as  fre q ue nc y c o u nt s u m maries b y st u d y peri o d (treat me nt peri o d a n d 
f oll o w- u p peri o d). 
A n  o ver vie w of A Es  will  prese nt t he  n u m ber a n d perce nta ge of partici pa nts  wit h  a n y A E,  A Es 
wit h o utc o me of deat h, seri o us A Es, a n d  A Es lea di n g t o disc o nti n uati o n of I P, as well as A Es 
lea di n g t o wit h dra wal fr o m st u d y . 
Se parate  A E ta bles  will  be  pr o vi de d ta ki n g i nt o c o nsi derati o n relati o ns hip as  assesse d b y t he 
i n vesti gat or, seri o us ness, deat h a n d e ve nts lea di n g t o disc o nti n uati o n of I P. 
A n  a d diti o nal ta ble will  prese nt  n u m ber a n d perce nta ge of  partici pa nts  wit h  m ost c o m m o n 
A Es.  M ost c o m m o n (e. g., fre q ue nc y of > x %, ≥x %) will be defi ne d i n t he S A P. 
 
 
Ke y partici pa nt i nf or mati o n will be  prese nte d f or  partici pa nts  wit h  A Es  wit h  o utc o me of deat h, 
seri o us A Es, a n d A Es lea di n g t o disc o nti n uati o n of I P. 
A n  A E listi n g  f or t he safet y a nal ysis set will  c o ver details  f or eac h i n di vi d ual A E.  
C CI
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F ull details  of A E  a nal yses  will be  pr o vi de d i n t he S A P.  
Treat me nt  Peri o d  
T he  f oll o wi n g e ve nts are c o nsi dere d treat me nt peri o d relate d:  
•  
A d verse e ve nts wit h a n  o nset date  o n or after dr u g  deli ver y date  t hr o u g h Visit 2 or, if Visit 
2 is n ot a vaila ble, date of last c o ntact  
•  
W orse ni n g of  pre-e xisti n g e ve nts o n or after dr u g  deli ver y  date  
•  
A d verse e ve nts start i n g d uri n g treat me nt peri o d a n d e xte n di n g i nt o 3 0- da y f oll o w- u p 
peri o d.  
 
F oll o w- U p  Peri o d  
T he 3 0- da y F oll o w -u p Peri o d be gi ns after Visit 2.  
9. 4. 4  
E v al u ati o n  of  SI L S 2  Liter ac y  T hres h ol d  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
9. 5  
I nteri m A n al yses  
N o  i nteri m a nal yses  are pla n ne d  f or t his st u d y. 
9. 6  
D at a  M o nit ori n g  C o m mittee  
T here  is n o Data M o nit ori n g C o m mittee  f or t his st u d y. 
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1 0  
S U P P O R TI N G  D O C U M E N T A TI O N  A N D  O P E R A TI O N A L 
C O N SI D E R A TI O N S  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 1  
A P P E N DI C E S  
A p pe n di x A.  
Re g ulat or y,  Et hical,  a n d St u d y  O versi g ht  C o nsi derati o ns  
A p pe n di x B.  
A d verse  E ve nts:  Defi niti o ns  a n d Pr oce d ures  f or Rec or di n g, E val uati n g, 
F oll o w -u p, a n d Re p orti n g   
A p pe n di x C.  
C utter  E val uati o n  of  Dr u g  Acc o u nta bilit y  C o m plia nce  
 
 
 
A p pe n di x E.  
A b bre viati o ns  & Defi niti o ns  
A p pe n di x F.  
Pr ot oc ol A me n d me nt Hist or y  
A p pe n di x G.  
Refere nces  
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A p pe n di x  A Re g ul at or y,  Et hic al,  a n d  St u d y  O versi g ht  C o nsi der ati o ns  
A 1  
Re g ul at or y  a n d  Et hic al  C o nsi der ati o ns  
•  
T his  st u d y will  be c o n d ucte d i n acc or da nce wit h  t he pr ot oc ol a n d wit h  t he f oll o wi n g: 
− 
C o nse ns us et hical pri nci ples  deri ve d fr o m i nter nati o nal g ui deli nes i ncl u di n g t he 
Declarati o n of Helsi n ki a n d  C o u ncil f or I nter nati o nal Or ga nizati o ns of Me dical 
Scie nces ( CI O M S) I nter nati o nal Et hical G ui deli nes  (W orl d Me dical Or ga nizati o n 
1 9 9 6 )  
− 
A p plica ble I C H G o o d Cli nical  Practice  ( G C P) G ui deli nes  (I nter nati o nal C o nfere nce 
o n Har m o nizati o n of Tec h nical Re q uire me nts of P har mace uticals f or H u ma n Use 
1 9 9 6 )  
− 
A p plica ble la ws a n d re g ulati o ns 
•  
T he pr ot oc ol, pr ot oc ol a me n d me nts, I C F, I n vesti gat or Br oc h ure, a n d ot her rele va nt 
d oc u me nts (e. g., a d vertise me nts) m ust be s u b mitte d t o a n I R B b y t he i n vesti gat or a n d 
re vie we d a n d a p pr o ve d b y t he I R B bef ore t he st u d y is i nitiate d. 
•  
A n y a me n d me nts t o t he pr ot oc ol will re q uire I R B a n d a p plica ble Re g ulat or y A ut h orit y 
a p pr o val bef ore i m ple me ntati o n of c ha n ges  ma de  t o t he st u d y desi g n, e xce pt f or c ha n ges 
necessar y t o eli mi nate a n i m me diate hazar d t o st u d y partici pa nts.  
•  
Astra Ze neca will be res p o nsi ble f or o btai ni n g t he re q uire d a ut h orizati o ns t o c o n d uct t he 
st u d y fr o m t he c o ncer ne d Re g ulat or y A ut h orit y. T his res p o nsi bilit y ma y  be dele gate d  t o a 
C R O b ut t he acc o u nta bilit y re mai ns wit h Astra Ze neca.  
 
Re g ul at or y Re p orti n g  Re q uire me nts  f or S A Es  
•  
Pr o m pt n otificati o n b y t he i n vesti gat or t o t he s p o ns or of a S A E is esse ntial s o t hat le gal 
o bli gati o ns a n d et hical res p o nsi bilities t o war ds t he safet y of partici pa nts  a n d t he safet y of 
a st u d y i nter ve nti o n u n der cli nical i n vesti gati o n are met.  
•  
T he s p o ns or has a le gal res p o nsi bilit y t o n otif y b ot h t he l ocal re g ulat or y a ut h orit y a n d 
ot her re g ulat or y a ge ncies a b o ut t he safet y of a st u d y i nter ve nti o n u n der cli nical 
i n vesti gati o n. T he s p o ns or will c o m pl y wit h c o u ntr y-s pecific re g ulat or y re q uire me nts 
relati n g t o safet y re p orti n g t o t he re g ulat or y a ut h orit y, I nstit uti o nal Re vie w  B oar ds (I R Bs) 
a n d i n vesti gat ors. 
•  
F or all st u dies e xce pt t h ose utilizi n g me dical de vices i n vesti gat or safet y re p orts m ust be 
pre pare d  f or s us pecte d u ne x pecte d  seri o us a d verse reacti o ns  ( S U S A R) acc or di n g t o l ocal 
re g ulat or y re q uire me nts a n d s p o ns or p olic y a n d f or war de d t o i n vesti gat ors as necessar y.  
•  
A n  i n vesti gat or w h o  recei ves a n i n vesti gat or safet y re p ort descri bi n g  a S A E  or ot her 
s pecific safet y i nf or mati o n (e. g., s u m mar y or listi n g of S A Es)  fr o m t he s p o ns or will 
re vie w a n d t he n file it al o n g wit h t he U S PI a n d will n otif y t he I R B, if a p pr o priate 
acc or di n g t o l ocal re q uire me nts.  

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A 2  
Fi n a nci al  Discl os ure  
I n vesti gat ors a n d s u b-i n vesti gat ors will  pr o vi de t he s p o ns or wit h  s ufficie nt, acc urate  fi na ncial 
i nf or mati o n as re q ueste d t o all o w t he s p o ns or t o s u b mit c o m plete a n d acc urate fi na ncial 
certificati o n or discl os ure state me nts t o t he a p pr o priate re g ulat or y a ut h orities. I n vesti gat ors 
are res p o nsi ble f or pr o vi di n g i nf or mati o n o n fi na ncial i nterests d uri n g t he c o urse of  t he st u d y 
a n d f or 1 year after c o m pleti o n of t he st u d y. 
A 3  
I nf or me d C o nse nt  Pr ocess  
•  
T he  i n vesti gat or or his/ her re prese ntati ve will  e x plai n t he nat ure  of t he st u d y t o t he s u bject 
a n d a ns wer all q uesti o ns re gar di n g t he st u d y. 
•  
S u bjects m ust be i nf or me d t hat  t heir partici pati o n is v ol u ntar y, a n d t he y are free t o ref use 
t o partici pate a n d ma y wit h dra w t heir c o nse nt at a n y ti me a n d f or a n y reas o n d uri n g t he 
st u d y. Partici pa nts will  be  re q uire d t o si g n a state me nt of i nf or me d c o nse nt t hat meets  t he 
re q uire me nts of 2 1 C F R 5 0 (U S F o o d a n d Dr u g A d mi nistrati o n 2 0 1 8 ), l ocal re g ulati o ns, 
I C H g ui deli nes (I nter nati o nal C o nfere nce o n Har m o nizati o n of Tec h nical Re q uire me nts 
of P har mace uticals f or H u ma n Use 1 9 9 6 ), Healt h I ns ura nce P orta bilit y  a n d 
Acc o u nta bilit y Act  ( HI P A A) re q uire me nts, w here  a p plica ble, a n d t he I R B or st u d y ce nter. 
•  
T he  s o urce m ust i ncl u de a state me nt t hat writte n  i nf or me d c o nse nt  was  o btai ne d bef ore 
t he partici pa nt was e nr olle d i n t he st u d y a n d t he date t he writte n  c o nse nt was o btai ne d. 
T he a ut h orize d pers o n o btai ni n g t he i nf or me d c o nse nt m ust als o si g n t he I C F. 
•  
Partici pa nts  m ust be re-c o nse nte d t o t he m ost  c urre nt  versi o n of t he I C F(s) d uri n g t heir 
partici pati o n i n t he st u d y.  
•  
A c o p y of t he I C F(s) m ust  be pr o vi de d  t o t he partici pa nt.  
A 4  
D at a  Pr otecti o n  
•  
S u bjects will be assi g ne d a u ni q ue i de ntifier b y t he s p o ns or. A n y s u bject/ partici pa nt 
rec or ds or datasets t hat are tra nsferre d t o t he s p o ns or will c o ntai n t he i de ntifier o nl y; 
s u bject/ partici pa nt na mes  or a n y i nf or mati o n w hic h  w o ul d ma ke  t he s u bject/ partici pa nt 
i de ntifia ble will n ot be tra nsferre d. 
•  
T he s u bject/ partici pa nt m ust be  i nf or me d t hat his/ her pers o nal st u d y-relate d data will be 
use d  b y t he s p o ns or i n acc or da nce wit h  l ocal data  pr otecti o n  la w. T he  le vel of discl os ure 
a n d use of t heir data m ust als o be e x plai ne d t o t he partici pa nt i n t he i nf or me d c o nse nt  
•  
T he partici pa nt m ust be i nf or me d t hat his/ her st u d y d oc u me n ts i ncl u di n g t he Tar gete d 
Me dical  a n d Me dicati o n  Hist or y  f or m ma y  be e xa mi ne d b y Cli nical  Q ualit y  Ass ura nce 
a u dit ors or ot her a ut h orize d pers o n nel a p p oi nte d b y t he s p o ns or, b y a p pr o priate I R B 
me m bers, a n d b y i ns pect ors fr o m re g ulat or y a ut h orities.  

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A 5  
Disse mi n ati o n  of  Cli nic al  St u d y  D at a  
A descri pti o n  of t his cli nical st u d y  will  be a vaila ble o n htt ps://astraze necacli nicaltrials.c o m  a n d 
htt ps:// w w w.cli nicaltrials. g o v  as will t he s u m mar y of t he st u d y res ults w he n t he y are 
a vaila ble. T he  cli nical st u d y a n d/ or s u m mar y of st u d y res ults ma y  als o be a vaila ble o n ot her 
we bsites acc or di n g t o t he re g ulati o ns of t he c o u ntries i n w hic h t he st u d y is c o n d ucte d. 
A 6  
D at a  Q u alit y  Ass ur a nce  
•  
All  partici pa nt  data relati n g t o t he st u d y will  be rec or de d o n e C R F u nless  tra ns mitte d t o 
t he s p o ns or or desi g nee electr o nicall y (e. g., la b orat or y data). T he i n vesti gat or is 
res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y p h ysicall y or 
electr o nicall y si g ni n g t he e C R F. 
•  
T he  i n vesti gat or m ust  mai ntai n  acc urate d oc u me ntati o n (s ource  data)  t hat s u p p orts t he 
i nf or mati o n e ntere d i n t he e C R F. 
•  
T he  i n vesti gat or m ust  per mit  st u d y-relate d m o nit ori n g, a u dits, I R B re vie w, a n d re g ulat or y 
a ge nc y i ns pecti o ns a n d pr o vi de direct access t o s o urce data d oc u me nts.  
•  
M o nit ori n g details descri bi n g strate g y (e. g., ris k- base d i nitiati ves i n o perati o ns a n d 
q ualit y s uc h as Ris k Ma na ge me nt a n d Miti gati o n Strate gies a n d A nal ytical Ris k -Base d 
M o nit ori n g), met h o ds, res p o nsi bilities, a n d re q uire me nts, i ncl u di n g ha n dli n g of 
n o nc o m plia nce iss ues a n d m o nit ori n g  tec h ni q ues (ce ntral, re m ote, or o n-site m o nit ori n g) 
are pr o vi de d i n t he M o nit ori n g Pla n. 
•  
T he  s p o ns or or desi g nee  is res p o nsi ble f or t he data  ma na ge me nt of t his st u d y i ncl u di n g 
q ualit y c hec ki n g of t he data. 
•  
T he  s p o ns or ass u mes  acc o u nta bilit y f or acti o ns dele gate d  t o ot her i n di vi d uals (e. g., 
C o ntract Researc h Or ga nizati o ns).  
•  
St u d y m o nit ors will  perf or m  o n g oi n g s o urce data  verificati o n  t o c o nfir m t hat data  e ntere d 
i nt o t he e C R F b y a ut h orize d site pers o n nel are acc urate, c o m plete, a n d verifia ble fr o m 
s o urce d oc u me nts; t hat t he safet y a n d ri g hts of partici pa nts are bei n g pr otecte d; a n d t hat 
t he st u d y is bei n g c o n d ucte d i n acc or da nce wit h t he c urre ntl y a p pr o ve d pr ot oc ol a n d a n y 
ot her st u d y a gree me nts, I C H G C P  (I nter nati o nal C o nfere nce o n Har m o nizati o n of 
Tec h nical Re q uire me nts of P har mace uticals f or H u ma n Use 1 9 9 6 ), a n d all a p plica ble 
re g ulat or y re q uire me nts. 
•  
Rec or ds a n d d oc u me nts, i ncl u di n g e-si g ne d I C Fs, pertai ni n g t o t he c o n d uct of t his st u d y 
m ust be retai ne d b y t he i n vesti gat or f or 1 5 years after st u d y c o m pleti o n u nless l ocal 
re g ulati o ns or i nstit uti o nal p olicies re q uire a l o n ger rete nti o n peri o d. N o rec or ds ma y be 
destr o ye d d uri n g t he rete nti o n peri o d wit h o ut t he writte n a p pr o val of t he s p o ns or. N o 
rec or ds ma y  be tra nsferre d t o a n ot her l ocati o n or  part y  wit h o ut writte n  n otificati o n  t o t he 
s p o ns or. 

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A 7  
S o urce  D oc u me nts  
•  
S o urce d oc u me nts pr o vi de e vi de nce f or t he e xiste nce  of t he partici pa nt  a n d s u bsta ntiate 
t he i nte grit y of t he data c ollecte d. S o urce d oc u me nts are file d wit h t he C M O G. 
Data  re p orte d o n t he e C R F or  e ntere d i n t he e C R F t hat are tra nscri be d fr o m s o urce d oc u me nts 
m ust be c o nsiste nt wit h t he s o urce d oc u me nts or t he discre pa ncies m ust be e x plai ne d.  
A 8  
St u d y  a n d  St u d y  Site  St art  a n d  Cl os ure  
T he  st u d y start date  is t he date o n w hic h  t he cli nical st u d y will  be o pe n f or recr uit me nt of 
s u bjects. 
T he  first act of recr uit me nt is t he date  t he a d vertisi n g is place d  w hic h  is t he first da y a s u bject 
ca n call f or pre -scree ni n g a n d will be t he st u d y start date. 
T he  s p o ns or desi g nee reser ves t he ri g ht t o ter mi nate t he st u d y at a n y ti me f or a n y reas o n at t he 
s ole discreti o n  of t he s p o ns or. St u d y sites will  be cl ose d u p o n st u d y c o m pleti o n. A st u d y site is 
c o nsi dere d cl ose d w he n all re q uire d d oc u me nts a n d st u d y s u p plies ha ve bee n c ollecte d a n d a 
st u d y site cl os ure visit has bee n perf or me d. 
Reas o ns  f or t he earl y cl os ure  of a st u d y site b y t he s p o ns or or i n vesti gat or ma y i ncl u de b ut are 
n ot li mite d t o: 
•  
Fail ure  of t he i n vesti gat or t o c o m pl y wit h  t he pr ot oc ol, t he re q uire me nts of t he I R B/I E C 
or l ocal healt h a ut h orities, t he s p o ns or’s pr oce d ures, or G C P g ui deli nes 
•  
I na de q uate recr uit me nt of  partici pa nts  b y t he i n vesti gat or 
•  
Disc o nti n uati o n of f urt her st u d y i nter ve nti o n de vel o p me nt  
 
If t he st u d y is pre mat urel y ter mi nate d or s us pe n de d, t he s p o ns or s hall pr o m ptl y i nf or m t he 
i n vesti gat ors, t he I R B, t he re g ulat or y a ut h orities, a n d a n y c o ntract researc h or ga nizati o n(s) 
use d  i n t he st u d y of t he reas o n f or ter mi nati o n or s us pe nsi o n, as s pecifie d b y t he a p plica ble 
re g ulat or y re q uire me nts. T he i n vesti gat or s hall pr o m ptl y i nf or m t he partici pa nt a n d s h o ul d 
ass ure a p pr o priate partici pa nt t hera p y a n d/ or f oll o w - u p. 
A 9  
P u blic ati o n  P olic y  
•  
T he  res ults of t his st u d y ma y  be p u blis he d or  prese nte d  at scie ntific meeti n gs.  If t his is 
f oresee n, t he i n vesti gat or a grees t o s u b mit all ma n uscri pts or a bstracts t o t he s p o ns or 
bef ore s u b missi o n. T his all o ws t he s p o ns or t o pr otect pr o prietar y i nf or mati o n a n d t o 
pr o vi de c o m me nts. 
•  
T he s p o ns or will c o m pl y wit h t he re q uire me nts f or p u blicati o n of st u d y res ults. I n 
acc or da nce  wit h  sta n dar d e dit orial a n d et hical practice,  t he s p o ns or will  ge nerall y  s u p p ort 

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p u blicati o n of m ultice nter st u dies o nl y i n t heir e ntiret y a n d n ot as i n di vi d ual site data. I n 
t his case, a c o or di nati n g i n vesti gat or will be desi g nate d b y m ut ual a gree me nt. 
•  
A ut h ors hi p will  be deter mi ne d  b y m ut ual a gree me nt  a n d i n li ne wit h  I nter nati o nal 
C o m mittee of Me dical J o ur nal E dit ors  
 

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A p pe n di x  B A d verse  E ve nts:  Defi niti o ns  a n d  Pr oce d ures  f or Rec or di n g, 
E v al u ati n g, F oll o w -u p, a n d Re p orti n g  
B 1  
Defi niti o n  of  a d verse  e ve nts 
A n  a d verse  e ve nt is t he de vel o p me nt of a n y u nt o war d me dical  occ urre nce i n a partici pa nt or 
cli nical st u d y partici pa nt a d mi nistere d a me dici nal pr o d uct a n d w hic h d oes n ot necessaril y 
ha ve a ca usal relati o ns hi p wit h t his treat me nt. A n  A E ca n t heref ore be a n y  u nfa v ora ble a n d 
u ni nte n de d si g n (e. g., a n a b n or mal la b orat or y fi n di n g), s y m pt o m (f or e xa m ple na usea, c hest 
pai n), or disease te m p orall y ass ociate d wit h t he use of a me dici nal pr o d uct, w het her or n ot 
c o nsi dere d relate d t o t he me dici nal pr o d uct. 
T he ter m  A E is use d t o i ncl u de b ot h seri o us a n d n o n-seri o us A Es a n d ca n i ncl u de a 
deteri orati o n  of a pre-e xisti n g me dical  occ urrence.  A n  A E ma y  occ ur at a n y ti me, i ncl u di n g 
r u n-i n or was h o ut peri o ds, e ve n if n o St u d y treat me nt has bee n a d mi nistere d. 
B 2  
Defi niti o ns  of  seri o us a d verse  e ve nt 
A seri o us a d verse  e ve nt is a n A E occ urri n g d uri n g a n y st u d y p hase (i.e., r u n-i n, treat me nt, 
was h o ut, f oll o w- u p), t hat f ulfils o ne or m ore of t he f oll o wi n g criteria:  
•  
Res ults  i n deat h  
•  
Is i m me diatel y life-t hreate ni n g 
•  
Re q uires i n-partici pa nt  h os pitalizati o n  or pr ol o n gati o n of e xisti n g  h os pitalizati o n  
•  
Res ults  i n persiste nt  or si g nifica nt disa bilit y  or  i nca pacit y. 
•  
Is a c o n ge nital a b n or malit y or birt h  defect  
•  
Is a n i m p orta nt me dical  e ve nt t hat ma y  je o par dize t he partici pa nt or ma y  re q uire me dical 
treat me nt t o pre ve nt o ne of t he o utc o mes liste d a b o ve. 
 
Life -t hre ate ni n g 
‘ Life-t hreate ni n g’ mea ns t hat t he partici pa nt was at i m me diate ris k of deat h fr o m t he  A E as it 
occ urre d, or it is s us pecte d t hat use or c o nti n ue d use of t he pr o d uct w o ul d res ult i n t he 
partici pa nt’s  deat h. ‘ Life-t hreate ni n g’ d oes n ot  mea n  t hat ha d a n A E  occ urre d  i n a m ore  se vere 
f or m it mi g ht ha ve ca use d deat h (e. g., he patitis t hat res ol ve d wit h o ut he patic fail ure). 
H os pit aliz ati o n  
O ut patie nt  treat me nt i n a n e mer ge nc y  r o o m is n ot  i n itself a seri o us A E, alt h o u g h t he reas o ns 
f or it ma y be (e. g., br o nc h os pas m, lar y n geal e de ma). H os pital a d missi o ns a n d/ or s ur gical 
o perati o ns pla n ne d bef ore or d uri n g a st u d y are n ot c o nsi dere d A Es if t he ill ness or disease 
e xiste d bef ore  t he partici pa nt was e nr olle d i n t he st u d y, pr o vi de d t hat it di d n ot deter i orate i n 
a n u ne x pecte d wa y d uri n g t he st u d y. 

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I m p ort a nt me dic al  e ve nt  or me dic al  tre at me nt 
Me dical a n d scie ntific j u d ge me nt s h o ul d be e xercise d i n deci di n g w het her a  case is seri o us i n 
sit uati o ns w here  i m p orta nt me dical  e ve nts ma y  n ot  be i m me diatel y life-t hreate ni n g or res ult i n 
deat h, h os pitalizati o n, disa bilit y, or i nca pacit y b ut ma y je o par dize t he partici pa nt or ma y 
re q uire me dical treat me nt t o pre ve nt o ne or m ore o utc o mes liste d i n t he defi niti o n of seri o us. 
T hese s h o ul d us uall y be c o n si dere d as seri o us. 
Si m pl y  st o p pi n g t he s us pect dr u g d oes  n ot mea n  t hat it is a n i m p orta nt me dical  e ve nt; me dical 
j u d ge me nt m ust be use d. 
•  
A n gi oe de ma n ot se vere e n o u g h t o re q uire i nt u bati o n b ut re q uiri n g i v h y dr oc ortis o ne 
treat me nt 
•  
He pat ot o xicit y ca use d b y  paraceta m ol  (aceta mi n o p he n) o ver d ose re q uiri n g treat me nt wit h 
N- acet ylc ystei ne 
•  
I nte nsi ve treat me nt i n a n e mer ge nc y  r o o m or at h o me f or  aller gic br o nc h os pas m  
•  
Bl o o d d yscrasias  (e. g., ne utr o pe nia or  a ne mia re q uiri n g bl o o d tra nsf usi o n, etc.) or 
c o n v ulsi o ns t hat d o n ot res ult i n h os pitalizati o n 
•  
De vel o p me nt of dr u g de pe n de nc y or dr u g a b use 
 
I nte nsit y r ati n g sc ale: 
•  
mil d  (a ware ness of si g n or s y m pt o m, b ut easil y t olerate d) 
•  
m o derate  ( disc o mf ort s ufficie nt t o ca use i nterfere nce wit h  n or mal  acti vities)  
•  
se vere (i nca pacitati n g, wit h i na bilit y t o perf or m n or mal acti vities) 
 
It is i m p orta nt t o disti n g uis h bet wee n seri o us a n d se vere A Es. Se verit y is a meas ure of 
i nte nsit y w hereas seri o us ness is defi ne d b y t he criteria i n A p pe n di x  B 2.  A n  A E of se vere 
i nte nsit y nee d n ot necessaril y be c o nsi dere d seri o us. F or e xa m ple, na usea t hat persists f or 
se veral h o urs ma y be c o nsi dere d se vere na usea, b ut n ot a S A E u nless it meets t he criteria 
s h o w n i n A p pe n di x  B 2.  O n t he ot her ha n d, a str o ke t hat res ults i n o nl y a li mite d de gree of 
disa bilit y  ma y  be c o nsi dere d a mil d  str o ke b ut w o ul d  be a S A E w he n  it satisfies t he criteria 
s h o w n i n A p pe n di x  B 2.  
B 3  
A G ui de  t o I nter preti n g t he C a us alit y  Q uesti o n  
W he n  ma ki n g a n assess me nt  of ca usalit y  c o nsi der t he f oll o wi n g fact ors w he n  deci di n g if t here 
is a ‘reas o na ble p ossi bilit y’ t hat a n A E ma y ha ve bee n ca use d b y t he dr u g. 
•  
Ti me C o urse. E x p os ure t o s us pect dr u g. Has t he partici pa nt a ct uall y recei ve d t he  s us pect 
dr u g? Di d  t he A E  occ ur i n a reas o na ble te m p oral relati o ns hi p t o t he a d mi nistrati o n  of t he 
s us pect dr u g? 

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C o nsiste nc y wit h k n o w n dr u g pr ofile. Was t he A E c o nsiste nt wit h t he pre vi o us 
k n o wle d ge of t he s us pect dr u g ( p har mac ol o g y a n d t o xic ol o g y) or dr u gs of t he  sa me 
p har mac ol o gical class? Or c o ul d t he A E be a ntici pate d fr o m its p har mac ol o gical 
pr o pe rties? 
•  
De -c halle n ge  e x perie nce. Di d  t he A E  res ol ve or i m pr o ve o n st o p pi n g or re d uci n g t he d ose 
of t he s us pect dr u g? 
•  
N o  alter nati ve  ca use. T he  A E  ca n n ot be reas o na bl y e x plai ne d b y a n ot her eti ol o g y s uc h as 
t he u n derl yi n g disease, ot her dr u gs, ot her h ost or e n vir o n me ntal fact ors.  
•  
Re -c halle n ge  e x perie nce. Di d  t he A E  re occ ur if t he s us pecte d dr u g was  rei ntr o d uce d after 
ha vi n g bee n st o p pe d? Astra Ze neca w o ul d n ot n or mall y rec o m me n d or s u p p ort a re- 
c halle n ge. 
•  
La b orat or y  tests. A s pecific la b orat or y i n vesti gati o n (if perf or me d) has c o nfir me d  t he 
relati o ns hi p. 
 
I n diffic ult  cases, ot her  fact ors c o ul d be c o nsi dere d s uc h as: 
•  
Is t his a rec o g nize d feat ure of o ver d ose of t he dr u g?  
•  
Is t here a k n o w n mec ha nis m?  
 
Ca usalit y  of ‘relate d’  is ma de if f oll o wi n g a re vie w of t he rele va nt data, t here is e vi de nce f or a 
‘reas o na ble p ossi bilit y’ of a ca usal relati o ns hi p f or t he i n di vi d ual case. T he e x pressi o n 
‘reas o na ble p ossi bilit y’ of a ca usal relati o ns hi p is mea nt t o c o n ve y, i n ge neral, t hat t here are 
facts (e vi de nce) or ar g u me nts t o s u g gest a ca usal relati o ns hi p. 
T he ca usalit y assess me nt is perf or me d base d o n t he a vaila ble data i ncl u di n g e n o u g h 
i nf or mati o n t o ma ke a n i nf or me d j u d g me nt. Wit h  n o a vaila ble facts or  ar g u me nts t o s u g gest a 
ca usal relati o ns hi p, t he e ve nt(s) will be assesse d as ‘ n ot relate d’.  
Ca usal  relati o ns hi p i n cases w here  t he disease u n der st u d y has  deteri orate d  d ue t o lac k of 
effect s h o ul d be classifie d as n o reas o na ble p ossi bilit y. 
B 4  
Me dic ati o n  Err or  
F or t he p ur p oses of t his cli nical st u d y a me dicati o n  err or is a n u ni nte n de d fail ure or mista ke  i n 
t he treat me nt pr ocess f or a n Astra Ze neca st u d y dr u g t hat eit her ca uses har m t o t he  partici pa nt 
or has t he p ote ntial t o ca use har m t o t he partici pa nt.  
A me dicati o n  err or  is n ot  lac k of efficac y of t he dr u g, b ut rat her a h u ma n or pr ocess relate d 
fail ure w hile t he dr u g is i n c o ntr ol of t he st u d y site staff or partici pa nt.  
Me dicati o n  err or i ncl u des sit uati o ns w here  a n err or. 

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occ urre d  
•  
was  i de ntifie d a n d i nterce pte d bef ore t he partici pa nt recei ve d t he dr u g  
•  
di d n ot occ ur, b ut circ u msta nces  were  rec o g nize d t hat c o ul d ha ve le d t o a n err or 
 
E xa m ples of e ve nts t o be re p orte d i n cli nical st u dies  as me dicati o n err ors: 
•  
Dr u g  n ot ta ke n as i n dicate d e. g., ta blet diss ol ve d  i n water w he n  it s h o ul d be ta ke n as a 
s oli d ta blet 
 
E xa m ples of  e ve nts t hat d o  n ot  re q uire re p orti n g as me dicati o n  err ors i n cli nical st u dies: 
•  
Partici pa nt  acci de ntall y  misse d  dr u g  d ose(s)  e. g., f or g ot t o ta ke me dicati o n  
•  
Acci de ntal  o ver d ose ( will be ca pt ure d as a n o ver d ose)  
•  
Partici pa nt  faile d t o ret ur n u n use d me dicati o n or  e m pt y pac ka gi n g  
•  
Err ors  relate d t o bac k gr o u n d a n d resc ue me dicati o n, or sta n dar d of care me dicati o n  i n 
o pe n- la bel st u dies, e ve n if a n Astra Ze neca pr o d uct 
 

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A p pe n di x  C C utter  E v al u ati o n  of  Dr u g  Acc o u nt a bilit y  C o m pli a nce  
T o better i m pr o ve p u blic healt h, Astra Ze neca is de vel o pi n g a n i n n o vati ve a p pr oac h i n 
healt hcare t hr o u g h use of a Tec h n ol o g y Assiste d Self- Selecti o n t o ol ( T A S S).  T his all o ws 
q ualifie d stati n -eli gi ble c o ns u mers w h o are n ot R x-treati n g t heir hi g h c h olester ol t o self-treat 
a n d i m pr o ve t heir healt h.  O ur a p pr oac h re q uires a sta n dar d e -c o m merce s ol uti o n t o dr u g 
deli ver y. T heref ore,  i n o ur Act ual Use St u d y ( A U S), we  will  f oll o w a real-w orl d  e-c o m merce 
a p pr oac h f or access a n d deli ver y of dr u g.  
T he Tec h n ol o g y- Assiste d C h olester ol Trial i n C o ns u mers ( T A C TI C) is a self -selecti o n ( S S) 
a n d A U S t hat will be c o n d ucte d as part of t he R x- t o-O T C S witc h pr o gra m f or r os u vastati n 5 
m g t o l o wer c h olester ol, o ne of t he ke y ris k fact ors t hat ca n lea d t o heart disease.  T his st u d y 
f ull y le vera ges i n n o vati ve a p pr oac hes t hat i ncl u de tec h n ol o g y-assiste d self-selecti o n a n d 
reselecti o n usi n g a We b A p p access t hat will bl oc k t he p urc hase of dr u g if “ D o n ot use” 
criteria are i n p utte d b y t he c o ns u mer. T he g oal of Astra Ze neca is t o desi g n t he A U S t o 
mi mic, t o  t he best  of o ur a bilit y i n a cli nical trial, t he “real-life” c o ns u mer e x perie nce  or deri n g 
a n d usi n g n o n- prescri pti o n r os u vastati n. 
N o n prescri pti o n r os u vastati n will O N L Y be a vaila ble t hr o u g h a n o nli ne p urc hase. It will n ot 
be a vaila ble o n s hel ves at retail st ores. Beca use t he p urc hase of t he d r u g will be d o ne o utsi de 
of a retail setti n g, Astra Ze neca pr o p oses t hat self -selecti o n, p urc hase, a n d ac q uisiti o n of t he 
pr o d uct be c o n d ucte d i n a si milar ma n ner i n t he A U S.  T his mea ns t hat c o ns u mers w o ul d use 
t he We b  A p p  t o a ns wer self-selecti o n q uesti o ns, a n d if eli gi ble t o recei ve t he pr o d uct, t he y are 
per mitte d t o c o m plete a n o nli ne p urc hase a n d ha ve t he dr u g deli vere d t o t he a d dress t he y 
pr o vi de d u p o n p urc hase. 
O ur pr o p ose d a p pr oac h t o pr o d uct deli ver y re q uires a t h or o u g h e val uati o n of t he ste ps we 
w o u l d nee d t o ta ke t o e ns ure t he i nte grit y of t he pr o d uct acc o u nta bilit y pr ocess w hile at t he 
sa me ti me e ns uri n g mi ni mal i m pact t o t he nat uralistic as pect of t he st u d y. As s u m marize d 
bel o w, d uri n g t he A U S, Astra Ze neca will ha ve a caref ull y desi g ne d a n d e xec ute d pr ocess f or 
ma na gi n g pr o d uct acc o u nta bilit y.  H o we ver, o ne ste p d uri n g t he o nli ne deli ver y pr ocess t hat 
we will n ot i nc or p orate i nt o o ur pr ocess is t he re q uire me nt f or a si g nat ure fr o m t he c o ns u mer 
u p o n deli ver y of dr u g.  Gi ve n t hat s hi p pers r o uti nel y deli ver pr o d ucts d uri n g t he da y, pe o ple 
ma y n ot be i ntereste d i n partici pati n g i n t he st u d y d ue t o t he a d de d b ur de n of nee di n g t o be 
h o me at t he ti me of deli ver y  f or si g nat ure. I n a d diti o n, if t he y d o partici pate, t he y ma y e n d u p 
missi n g da ys of t hera p y if t he y are n ot h o me t o si g n f or t heir deli ver y. Si nce s u bjects are 
re q uire d t o re- or der dr u g e ver y 4 5 or 9 0 da ys d uri n g t he c o urse of t he st u d y, t his iss ue is a real 
p ossi bilit y. W hile  a si g nat ure is n ot re q uire d, deli ver y of me dicati o n will  be  c o nfir me d b y  t he 
deli ver y c o m pa n y as o utli ne d bel o w.  N ote t hat i n o ur c urre nt e- c o m merce e n vir o n me nt, 
c o ns u mers are n ot re q uire d t o si g n f or me dicati o ns t hat c o me fr o m a n o nli ne p har mac y. 

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As pre vi o usl y state d, Astra Ze neca is c o m mitte d t o mai ntai ni n g t he i n te grit y of pr o d uct 
acc o u nta bilit y, a n d t he f oll o wi n g safe g uar ds a n d acc o m pa n yi n g d oc u me ntati o n de m o nstrate 
c o ntr ol of i n vesti gati o nal pr o d uct t hr o u g h t he e ntire pr ocess: 
•  
T he Astra Ze neca Ne war k pac ka gi n g site will be res p o nsi ble f or pac ka gi n g t he b ottles of  
dr u g w hic h will be s hi p pe d t o a pac ka gi n g a n d distri b uti o n ve n d or, Hi b bert. Hi b bert acts 
as a Ce ntral De p ot t o pre pare t he dr u g a n d   acc o m pa n yi n g d oc u me ntati o n ( Dr u g Facts 
La bel ( D F L), C o ns u mer I nf or mati o n Leaflet ( CI L), i n v oice/ pac ki n g sli p) f or s hi p me nt via 
a deli ver y ser vice.  T his ser vice, f or e xa m ple Fe d E x or U S P S, will pr o vi de a n a u dit trail 
via a trac ki n g n u m ber w hic h will  c o nfir m  t he l ocati o n of  t he dr u g d uri n g tra nsit a n d 
arri val at t he deli ver y a d dress pr o vi de d b y t he partici pa nt at t he ti me of p urc hase.  
I n ve nt or y will be c o nfi g ure d as a re g ulate d pr o d uct i n Hi b bert’s I n ve nt or y Ma na ge me nt 
S yste m.  Re g ulate d is defi ne d as e nc o m passi n g  pr o d uct t hat is  l ot c o ntr olle d, a n d/ or has 
a n Nati o nal Dr u g C o de  ( N D C), a n d/ or is g o ver ne d b y Prescri pti o n  Dr u g Mar keti n g  Act  
g ui deli nes. T his  c o nfi g urati o n tri g gers a d de d q ualit y c o ntr ol c hec ks i n t he Hi b bert 
i n ve nt or y s yste m a n d pr ocesses.  
•  
U p o n c o m pleti o n of a n o nli ne p urc hase b y t he s u bject, t he We b A p p has a c o ntr ol usi n g 
S hi p  E n gi ne ® tec h n ol o g y t o e ns ure t he s u bject is i n p utti n g a vali d maili n g a d dress.  
•  
I n t he A U S, t he i nitial s hi p me nt will be hel d b y t he We b A p p u ntil t he partici pa nt 
c o m pletes virt ual Visit 1 o nli ne wit h t he st u d y staff, t o c o nse nt a n d verif y t hat t he y are 
n ot pre g na nt/ breastfee di n g a n d/ or has se vere aller g y t o t he me dicati o n. O nce Visit 1 is 
c o m plete d, t he ce ntral i n vesti gat or or s u b - i n vesti gat or will a ut h orize a release of t he 
i nitial or der c o nfir mati o n fr o m t he We b A p p t hat is se nt t o t he Ce ntral De p ot.  Pr o vi de d 
t he partici pa nt has n o c ha n ges i n healt h as a d mi nistere d via t he We b A p p, s u bse q ue nt re-
or ders will a ut o maticall y tri g ger s hi p me nt t hr o u g h t he We b A p p t o t he Hi b bert Ce ntral 
De p ot i m me diatel y u p o n o nli ne p urc hase b y t he partici pa nt. E mails will als o   be use d t o 
i nf or m s u bjects w he n t he y ca n re or der. T he y will recei ve a re or der e mail at da y 2 5 f or a 
4 5- da y s u p pl y or der a n d at da y 4 5 f or a 9 0 da y s u p pl y or der. Partici pa nts  will  be t ol d at 
Visit  1 a n d at t he ti me Visit  2 is sc he d ule d, t o ret ur n all u n use d dr u g pr o d uct as well as 
e m pt y, use d b ottles after Visit 2 f or dr u g acc o u nta bilit y. D uri n g t he virt ual Visit 2, t he 
partici pa nt will pr o vi de a vis ual c o nfir mati o n of t he pac ka gi n g of st u d y material t o t he 
st u d y staff a n d c o nfir m it is rea d y f or ret ur ns s hi p me nt. T h ose partici pa nts w h o ref use t o 
se n d bac k t heir pill b ottles f or a fi nal pill c o u nt will be gi ve n t he o pti o n t o c o u nt t he pills 
wit h t he st u d y  pers o n nel via vi de o c o nfere nce at Virt ual  Visit 2.   T his will be rec or de d o n 
s o urce d oc u me ntati o n a n d t he e C R F. 
•  
T he  Hi b bert s yste m i nte grates wit h  t he We b  A p p.  
− 
T he Or der S hi p pe d n otificati o n will i ncl u de t he f oll o wi n g s hi p me nt data c o m prise d  
of i nf or mati o n  fr o m b ot h t he We b  A p p  a n d Hi b bert: 
o  
F ull partici pa nt  na me a n d  a d dress 

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Partici pa nt I D 
o  
Carrier a n d  S hi p pi n g Met h o d use d  f or S hi p pi n g  
o  
Q ua ntit y of Crest or  5 m g B ottle  s hi p pe d 
o  
L ot  N u m ber 
o  
Date  S hi p pe d 
o  
Date  Cli nicia n  Release d  (i nitial or der o nl y)  
o  
Date  Or der  Ca ncelle d (if  a p plica ble) 
o  
Trac ki n g N u m ber  
− 
T he  Or der  Deli vere d  n otificati o n  will  u p date s hi p me nt data  wit h  t he f oll o wi n g details: 
o  
Partici pa nt I D 
o  
Date  Deli vere d  
o  
Trac ki n g N u m ber  
•  
I n a d diti o n t o t he af ore me nti o ne d pr o d uct c o ntr ols, Astra Ze neca will se n d tra nsacti o nal 
e mails t o partici pa nts n otif yi n g t he m t hat t heir dr u g is bei n g s hi p pe d a n d t hat it is has 
bee n deli vere d t o t he a d dress t he y pr o vi de d at t he ti me t he y place d t he or der.  T he 
deli ver y e mail will als o c o ntai n a tele p h o ne n u m ber t o call if t he y di d n ot recei ve t heir 
or der. T hese e mails will s u p p ort i de ntificati o n  of  a n iss ue wit h  pr o d uct acc o u nta bilit y. If 
t he partici pa nt  di d n ot recei ve t heir dr u g s u p pl y, Hi b bert will i nitiate t he ma n ual o verri de 
pr ocess descri be d bel o w. 
•  
U p o n n otificati o n of a n y missi n g s hi p me nts or pr o d uct da ma ge, Hi b bert will ma n uall y 
i nitiate a re place me nt or der t o s hi p t o partici pa nt. A ma n ual or der place me nt c hec k is i n 
place f or ma xi m u m of t w o ( 2) per partici pa nt base d o n t he partici pa nt I D.  If t he 
partici pa nt re q uests a t hir d re place me nt or der, t he re q uest  will  be ele vate d t o Astra Ze neca  
a n d C o nce ntrics f or f urt her e val uati o n a n d a decisi o n o n ne xt ste ps. A n y a p pr o ve d 
re place me nt or der will be trac ke d via Hi b bert’s  s yste ms a n d t he ne w deli ver y  date  will be  
e ntere d i nt o t he St u d y A d mi n P ortal o nce recei ve d fr o m Hi b bert. W hile  missi n g 
s hi p me nts will be  a rare occ urre nc e, t he re place me nt or der pr ocess was p ut i n place t o 
e ns ure c o nti n uit y of treat me nt, a n d t o pre ve nt p ote ntial a b use of t he o nli ne or deri n g 
pr ocess.  
 
D oc u me ntati o n a n d a p pr o priate a u dit trails will be i n place t o e ns ure tracea bilit y of pr o d uct 
fr o m S p o ns or t o Ce ntral  De p ot, We b  A p p  t o Ce ntral  De p ot, a n d Ce ntral  De p ot t o t he deli ver y  
a d dress  pr o vi de d  b y c o ns u mer. See  attac he d Fl o wc hart f or Ma na ge me nt  of I n vesti gati o nal 
Pr o d uct i n t he A U S ( Fi g ure 1). 
 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 0 7  of 1 5 5  
 
Astra Ze neca  is re q uesti n g fee d bac k fr o m t he A ge nc y a b o ut t he i nter pretati o n a n d a p plicati o n 
of 2 1 C F R  3 1 2. 4 0 a n d 2 1 C F R  3 1 2. 5 7, 3 1 2. 5 9, 3 1 2. 6 1 a n d t hr o u g h 3 1 2. 6 2 as it relates t o t his 
n o vel A U S desi g n a n d n o re q uire me nt f or a si g nat ure f or t his pr o d uct u p o n arri val at t he 
deli ver y a d dress.  
FI G U R E  1: M a n a ge me nt  of I n vesti g ati o n al Pr o d uct  i n t he A U S  
 
Astra Ze neca  Ne war k L ocati o n ( m a n uf act urer) 
[ Pac ka ges dr u g a n d la bels b ottles “ Ca uti o n: Ne w  Dr u g — Li mite d  b y Fe deral ( or U nite d States) la w t o 
i n vesti gati o nal use.”] 
 
Astra Ze neca  Ne war k  L ocati o n  s hi ps dr u g b ottles  t o Ce ntral  De p ot  
[ A u dit Trail D oc u me ntati o n:  Pa per S hi p pi n g L o g wit h  s hi p me nt] 
 
St u d y s u bject places  a n o nli ne or der  fr o m t he We b  A p p  (We b  A p p)  
[ A u dit Trail D oc u me ntati o n: Or der Trac ki n g Re p ort]  
 
Or der  is place d  o n “ h ol d”  b y t he We b  A p p u ntil release d at Visit  1 f or  i nitial or der o nl y (We b A p p )  
[ A u dit Trail D oc u me ntati o n: Or der Trac ki n g Re p ort]  
 
St u d y partici pa nt me dical  hist or y  ta ke n b y t he C o nce ntrics Tele me dici ne Gr o u p  at Visit  1 (C M O G  cli nici a n ) 
[ A u dit Trail D oc u me ntati o n:  E D C s yste m or s o urce d oc u me ntati o n]  
 
If n o e xcl usi o ns f or  use are i de ntifie d, t he Ce ntr al  I n vesti gat or or  S u b-I a ut h orizes  t he dr u g t o be dis pe nse d t o 
t he partici pa nt (Ce ntr al PI – C M O G or S u b -I -C M O G ) 
[ A u dit Trail  D oc u me ntati o n:   Pr o d uct Dis pe nsi n g A ut h orizati o n  F or m] 1 
 
A Cli nicia n  will  t he n release t he dr u g “ h ol d” i n t he We b  A p p  (Cli nici a n  Le a d )  
[ A u dit Trail D oc u me ntati o n: Pr o d uct Release F or m]  
 
T he We b  A p p  will  release t he or der t o t he Ce ntral  De p ot  (We b  A p p)  
[ A u dit Trail D oc u me ntati o n: Or der Trac ki n g Re p ort]  
 
 
 
 
 
 
 
 
 
 
 
 
1 If e xcl usi o ns are i de ntifie d, t he Ce ntral I n vesti gat or or  S u b-I d oes  N O T a ut h orize t he dr u g  t o be  dis pe nse d [ A u dit 
Trail  D oc u me ntati o n: Pr o d uct Dis pe nsi n g A ut h orizati o n F or m, D oc u me nt ati o n of Deacti vati o n of  Acc o u nts, 
D oc u me ntati o n of Ca ncelle d Or ders] – n o dr u g  dis pe nse d  

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 0 8  of 1 5 5  
 
Ce ntral  De p ot s hi ps dr u g t o t he partici pa nt’s  a d dress  (Ce ntr al De p ot )2 
[ A u dit Trail D oc u me ntati o n:  Or der  Detail  a n d Usa ge  Re p ort]  
 
Tra nsacti o nal  e mails  se nt t o partici pa nt  w he n  dr u g is s hi p pe d a n d w he n  deli ver e d  wit h  details o n w hat 
t o d o if s hi p me nt is n ot recei ve d. 
[ A u dit Trail  D oc u me ntati o n:  Partici pa nt  C R M  Re p ort]  
 
Dr u g is trac ke d d uri n g s hi p me nt ( S hi p pi n g c o m p a ny )  
[ A u dit Trail  D oc u me ntati o n:  Or der  Detail  a n d Usa ge  Re p ort] 
 
Dr u g  is deli vere d  t o partici pa nt’s  a d dress ( S hi p pi n g c o m p a ny)3 
[ A u dit Trail D oc u me ntati o n:  Or der Detail  a n d Usa ge  Re p ort]  
 
Dr u g  b ottle  n u m ber is verifie d  b y partici pa nt  u p o n recei pt t hr o u g h defi ne d  met h o d (P artici p a nt )  
[ A u dit Trail D oc u me ntati o n:  Electr o nic c o nfir mati o n d oc u me ntati o n]  
 
Dr u g  i n ve nt or y is disc usse d  wit h partici pa nt  at V 2  (St u dy site st aff)4 
[ A u dit Trail  D oc u me ntati o n:   Dr u g Acc o u nta bilit y L o g mai ntai ne d  b y st u d y site staff] 
 
Dr u g  is s hi p pe d bac k  fr o m partici pa nt  t o st u d y site staff t o c o nfir m dr u g acc o u nta bilit y  (St u dy site) 
[ A u dit Trail D oc u me ntati o n: Dr u g Acc o u nta bilit y L o g mai ntai ne d b y st u d y site staff]  
 
Dr u g is  s hi p pe d bac k fr o m  st u d y site staff t o a q ualifie d t hir d-part y ve n d or  f or pr o d uct destr ucti o n. 
[ A u dit Trail D oc u me ntati o n: Pa per Dr u g S hi p pi n g L o g, Certificate of Destr ucti o n]  
 
 
 
 
 
 
 
 
 
 
 
 
2 Ce ntral De p ot S yste m will i nte grate  wit h t he We b A p p.  T he  Or der S hi p pe d  n otificati o n will i ncl u de  t he f oll o wi n g 
s hi p me nt data c o m prise d of i nf or mati o n fr o m b ot h t he We b A p p a n d Ce ntral De p ot: F ull partici pa nt na me a n d a d dress, 
Partici pa nt I D, Carrier a n d S hi p pi n g Met h o d  use d f or S hi p pi n g, Q ua ntit y of Crest or 5 m g B ottle s hi p pe d, L ot N u m ber, 
Date S hi p pe d, Dat e Cli nicia n Releas e d (i nitial or der o nl y), Date  Or der C a ncelle d (if a p plica ble), Trac ki n g N u m ber.  
T he Or der Deli vere d n otificati o n will u p date s hi p me nt data wit h t he f oll o wi n g details:  Partici pa nt I D, Date Deli vere d, 
Trac ki n g N u m ber  
 
3 If a s hi p me nt is missi n g or  pr o d uct  is da ma ge d, Ce ntral De p ot will ma n u all y i nitiate a re place me nt or der  t o s hi p t o 
t he partici pa nt. T his  will o nl y be per mitte d X 2  
 
4 T h ose  partici pa nts w h o ref use t o se n d bac k t heir pill b ottles f or a fi nal pill c o u nt  will be  gi ve n t he o pti o n  t o c o u nt t he pills wit h t he  
st u d y pers o n nel via vi de o c o nfere nce at Virt ual Visit 2.  T his will be rec or de d o n s o urce d oc u me ntati o n a n d t he e C R F  
 
 
 
 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 0  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n w it h a We b A p p ( C o m bi nati o n Pr o d uct) - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 1  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 2  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 3  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 4  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 5  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 6  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 7  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 8  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 1 9  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2 0  of 1 5 5  
 
A p pe n di x  E A b bre vi ati o ns  & Defi niti o ns  
A b bre vi ati o n  or  s peci al 
ter m 
E x pl a n ati o n  
A A D  
As k  a D oct or  
A A D B U  
As k  a D oct or  Bef ore  Use  
A C C  
A merica n  C olle ge  of  Car di ol o g y  
A E  
A d verse  E ve nt  
A H A  
A merica n  Heart  Ass ociati o n  
AI D S  
Ac q uire d  I m m u ne Deficie nc y  S y n dr o me  
A S C V D  
At her oscler otic  Car di o vasc ular  Disease  
A U S  
Act ual  Use St u d y  
B P  
Bl o o d  Press ure  
C A C  
C or o nar y  Arter y  Calci u m  
C A N -S P A M  
C o ntr olli n g  t he Assa ult  of  N o n -S olicite d  P or n o gra p h y  a n d Mar keti n g  
C F R  
C o de  of  Fe deral  Re g ulati o ns  
CI  
C o nfi de nce  I nter val 
CI L  
C o ns u mer  I nf or mati o n Leaflet  
C M O G  
Ce ntral  Me dical  O perati o ns  Gr o u p  
C O N S O R T  
C o ns oli date d  Sta n dar ds  of  Re p orti n g  Trials  
C R O  
C o ntract  Researc h  Or ga nizati o n  
C S A  
Cli nical  St u d y  A gree me nt  
C S P  
Cli nical  St u d y  Pr ot oc ol  
C S R  
Cli nical  St u d y  Re p ort  
C V  
Car di o vasc ular  
C V D  
Car di o vasc ular  Disease  
D B L  
Data  Base  L oc k  
D F L  
Dr u g  Facts  La bel  
D N U  
D o  N ot  Use  
e C R F 
Electr o nic  Case  Re p ort  F or m  
e Diar y 
Electr o nic  Diar y  
F D A  
U. S.  F o o d  a n d Dr u g  A d mi nistrati o n  
G C P  
G o o d  Cli nical  Practice  
H D L -C  
Hi g h -De nsit y  Li p o pr otei n  - C h olester ol  
HI P A A  
Healt h  I ns ura nce P orta bilit y  a n d Acc o u nta bilit y  Act  
HI V  
H u ma n  I m m u n o deficie nc y Vir us  
H R  
Hazar d  Rati o  
Hs -C R P  
Hi g h -se nsiti vit y C-reacti ve Pr otei n  
I C F 
I nf or me d C o nse nt  F or m  
I C H 
I nter nati o nal C o nfere nce  o n  Har m o nizati o n  

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2 1  of 1 5 5  
 
A b bre vi ati o n  or  s peci al 
ter m 
E x pl a n ati o n  
I M S 
I nterc o nti ne ntal Me dical  Statistics  
i P R 
i P R P har mace uticals  (a ma n ufact uri n g  site f or Astra Ze neca)  
I R B 
I nstit uti o nal Re vie w  B oar d  
I T T 
I nte nt t o Treat  
L B  
L o wer  B o u n d  
L C  
La bel  C o m pre he nsi o n  
L D L- C 
L o w -De nsit y  Li p o pr otei n  - C h olester ol  
me d D R A  
Me dical  Dicti o nar y  f or Re g ulat or y  Acti vities  
m g  
Milli gra ms  
MI  
M y ocar dial  I nfarcti o n 
N C E P  
Nati o nal  C h olester ol  E d ucati o n  Pr o gra m  
O T C  
O ver -t he-C o u nter  
P A D  
Peri p heral  Arter y  Disease  
Partici pa nt  
A n y s u bject w h o e nr olls i n t he st u d y 
P C E  
P o ole d  C o h ort  E q uati o n  
PI  
Pri nci pal  I n vesti gat or 
P O  
P ost Office  
P T  
Preferre d  Ter m  
R E A L M  
Ra pi d  Esti mate  of  A d ult  Literac y  i n Me dici ne  
R E F  
Ris k  E n ha nci n g  Fact or  
R x  
Prescri pti o n  
S A E  
Seri o us  A d verse  E ve nt  
Sa M D  
S oft ware  as a Me dical  De vice  
S A P  
Statistical  A nal ysis  Pla n  
S M T  
St u d y  Ma n date d  Testi n g  
S o A  
Sc he d ule  of  Acti vities  
S O C  
S yste m  Or ga n  Class  
S S  
Self -Selecti o n  
S u bject  
All s u bjects w h o c o m pletes t he o nli ne pre -scree ni n g eit her o nli ne or b y calli n g t he 
Call Ce nter  
S U S A R  
S us pecte d  U ne x pecte d  Seri o us  A d verse  Reacti o n  
T A S S  
Tec h n ol o g y -Assiste d  Self -Selecti o n  
T C  
T otal  C h olester ol  
T G  
Tri gl yceri des  
T O C  
Ta ble  of  C o nte nts  
U P T  
Uri ne  Pre g na nc y  Test  
U S PI  
U nite d  States  Prescri bi n g  I nf or mati o n 
We b A p p  
We b  A p plicati o n  

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2 3  of 1 5 5  
 
A p pe n di x  F Pr ot oc ol A me n d me nt Hist or y  
Pr ot oc ol A me n d me nt  S u m m ar y  of C h a n ges  T a ble  
 
D O C U M E N T  HI S T O R Y  
D oc u me nt  
D ate  
A me n d me nt 7  
1 4 Dec 2 0 2 2  
A me n d me nt  6 
0 1 Se p 2 0 2 2  
A me n d me nt  5 
1 1 A pr 2 0 2 2  
A me n d me nt  4 
1 4 -Oct -2 0 2 1  
A me n d me nt  3 
2 2 -J ul-2 0 2 1  ( never i m ple m 5e nte d) 
A me n d me nt  2 
1 6 -J u n-2 0 2 1  
A me n d me nt  1 
1 1 -M ar -2 0 2 1  
Ori gi n al  Pr ot oc ol  
1 7 -J uly-2 0 2 0  
 
A me n d me nt  7 (1 4 Dec 2 0 2 2 ) 
O ver all R ati o n ale f or t he A me n d me nt:  
Secti o n # a n d 
N a me  
Descri pti o n of 
C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -
s u bst a nti al 
Secti o n 1. 1 a n d 
Secti o n 3 
 
S y n o psis a n d 
O bjecti ves a n d 
E n d p oi nts 
A d de d “c orrectl y 
self-i de ntif y” t o t he 
e n d p oi nt descri pti o n 
Pr o vi de clarit y  
N o n -s u bsta ntial 
Secti o n 1. 1 a n d 
Secti o n 3 
 
S y n o psis a n d 
O bjecti ves a n d 
E n d p oi nts 
A d de d “(i.e. 
partici pa nt w h o are 
l o n git u di nall y 
c o m plia nt)” 
Pr o vi de clarit y  
N o n -s u bsta ntial 

Cli nical St u d y Pr ot oc ol  – v 8. 0  
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Secti o n # a n d 
N a me  
Descri pti o n of 
C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -
s u bst a nti al 
Secti o n 1. 1, 
Secti o n 5, a n d 
Secti o n 5. 2 
 
S y n o psis, St u d y 
P o p ulati o n, 
I ncl usi o n Criteria 
 
 
Clarifie d I ncl usi o n 
Criteria # 2 – 
re m o ve d refere nce t o 
“e nr olle d” t o ac hie ve 
o ur q u ota o n fe males 
u n der 5 0 years of a ge  
I n or der t o ac hie ve t he 
q u ota of n = 5 0 of 
fe males u n der 5 0 years 
of a ge, s u bjects ha d t o 
c o m plete t he i nitial 
T A S S assess me nt 
w hic h occ u rs bef ore 
e nr oll me nt. As s uc h, 
t o ac hie ve t he q u ota, it 
was n ot necessar y t o 
e nr oll t he partici pa nt 
w hic h mea ns si g ni n g 
t he I C F. 
S u bsta ntial  
Secti o n 1. 1 a n d 
Secti o n 5. 3 
 
S y n o psis a n d 
E xcl usi o n Criteria  
A d de d t he f ull SI L S 2 
q uesti o n bei n g as ke d 
Pr o vi de clarit y  
N o n -s u bsta ntial 
Secti o n 1. 1 a n d 
Secti o n 9. 1 
 
S y n o psis a n d 
Statistical 
H y p ot heses 
N ull h y p ot heses 
e q uati o ns u p date d 
fr o m “ =” t o “ ≤” a n d 
“ ≥” res pecti vel y 
Pr o vi de clarit y. T he 
u p dati n g of t he 
e q uati o n d oes n’t 
c ha n ge t he testi n g of 
t he statistical 
h y p ot heses.   
N o n -s u bsta ntial 
Secti o n 1. 1 a n d 
Secti o n 9. 4. 2. 1 
 
S y n o psis a n d 
Pri mar y 
E n d p oi nt(s) 
U p date d “ w here t he 
L D L - C val ue e ntere d 
b y t he partici pa nt at 
i nitial selecti o n a n d 
verifie d b y t he 
C M O G will ser ve as 
Baseli ne” t o “ w here 
t he verifie d L D L-C 
val ue at i nitial 
selecti o n will ser ve 
as Baseli ne” 
Pr o vi de clarit y  
N o n -s u bsta ntial 

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1 2 5  of 1 5 5  
 
Secti o n # a n d 
N a me  
Descri pti o n of 
C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -
s u bst a nti al 
Secti o n 3. 1  
 
E n d p oi nt Rati o nale  
 
 
U p date d fr o m “ uses 
t he pill c o u nt” t o 
“ uses t he pill c o u nt 
or e Diar y” f or 
o verall c o m plia nce 
wit h d osi n g 
Partici pa nt ma y n ot 
ret ur n pills b ut ha ve 
bee n hi g hl y c o m plia nt 
wit h c o m pleti n g t he 
e Diar y or a partici pa nt 
ma y n ot ha ve bee n as 
c o m plia nt wit h e Diar y 
b ut ret ur ne d all pills.  
T his will all o w us t o 
use w hic he ver has t he 
m ost data f or t he 
c o m plia nce calc ulati o n  
N o n -s u bsta ntial 
Secti o n 4. 4  
 
E n d of St u d y 
Defi niti o n  
U p date d defi niti o n of 
“c o m pleti n g t he 
st u d y” 
T o pr o vi de clarit y t hat 
partici pa nts w h o 
disc o nti n ue wit h 
s ufficie nt me dical a n d 
me dicati o n hist or y t o 
deter mi ne a fi nal use 
o utc o me (a n d d o n ot 
wit h dra w) are 
c o nsi dere d t o ha ve 
c o m plete d t he st u d y 
N o n -s u bsta ntial 
Secti o n 7. 2  
 
Partici pa nt 
Wit h dra wal fr o m 
t he St u d y 
Cate g orize d 
wit h dra wals as S S 
wit h dra wals or A U S 
I T T wit h dra wals 
Pr o vi de f urt her clarit y  
N o n -s u bsta ntial 
Secti o n 8. 4. 3  
 
Ca usalit y 
C ollecti o n  
U p date d q uesti o n 
as ke d o n ca usalit y t o 
reflect h o w it is 
as ke d o n s o urce 
Pr o vi de clarit y  
N o n -s u bsta ntial 
Secti o n 8. 6. 2  
 
P har mac o d y na mics  
U p date d fr o m 
“ P har mac o d y na mics 
are n ot e val uate d i n 
t his st u d y” t o 
“ P har mac o d y na mics 
are e val uate d as part 
of t he L D L- C 
Pr o vi de clarit y  
N o n -s u bsta ntial 

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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2 6  of 1 5 5  
 
Secti o n # a n d 
N a me  
Descri pti o n of 
C h a n ge  
Brief R ati o n ale  
S u bst a nti al/ N o n -
s u bst a nti al 
re d ucti o n efficac y 
e val uati o n” 
Secti o n 9. 3  
 
P o p ulati o ns f or 
A nal yses  
U p date d defi niti o n of 
pre- scree ne d 
p o p ulati o n 
Pr o vi de f urt her clarit y  
N o n -s u bsta ntial 
Secti o n 9. 3 a n d 
Secti o n 9. 4. 3 
 
P o p ulati o ns f or 
A nal yses, 
Statistical A nal yses  
U p date d defi niti o n of 
safet y p o p ulati o n 
Pr o vi de f urt her clarit y 
as it is u n k n o w n as t o 
w he n a partici pa nt t o o k 
a first d ose s o we 
defi ne d t hat first d ose 
t o be t he date dr u g was 
deli vere d  
N o n -s u bsta ntial 
Secti o n 9. 4. 1. 3  
 
Miti gati o n Pla n  
A d de d w or di n g t o 
c o nfir m t hat A Z a n d 
Cle vela n d Cli nic are 
bli n de d t o t he i m pact 
t hat p ost-st u d y 
miti gati o ns will ha ve 
o n t he st u d y res ults 
 
 
N o n -s u bsta ntial 
Secti o n 9. 4. 1. 3  
 
Miti gati o n Pla n  
A d de d miti gati o n o n 
missi n g L D L -C 
retests t o Ta ble 9- 4 
t hat was a d de d t o 
S A P  
E ns ure t he a pri ori 
miti gati o n o n missi n g 
L D L -C retest was 
ca pt ure d i n t he C S P 
after bei n g i de ntifie d i n 
t he S A P v 4. 0 
S u bsta ntial  
Secti o n 9. 4. 1. 4  
 
Ma na gi n g 
Varia bilit y of La b, 
Bl o o d Press ure, 
a n d Waist 
Circ u mfere nce 
fr o m Differe nt 
S o urces  
A d de d h o w waist 
circ u mfere nce 
varia bilit y w o ul d be 
ha n dle d 
Pr o vi de clarit y  
N o n -s u bsta ntial 
C CI

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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 2 9  of 1 5 5  
 
A p pe n di x  G Refere nces  
Astr a Ze nec a P h ar m ace utic als L P 2 0 2 1 
Astra Ze neca P har mace uticals L P. C R E S T O R (r os u vasti n calci u m) [ Prescri bi n g I nf or mati o n]. 
U. S. F o o d a n d Dr u g A d mi nistrati o n we bsite. 
htt ps:// w w w.access data.f da. g o v/s pl/ data/ 0 8 0 3 9 4 0 2- 2a 6 0- 4 5 9 9- 8 3 b 5-
1c 6 3 b 8 5ea d 7 0/ 0 8 0 3 9 4 0 2- 2a 6 0- 4 5 9 9- 8 3 b 5- 1c 6 3 b 8 5ea d 7 0. x ml  
B ull a n o et al 2 0 0 6 
B ulla n o M F, Wertz D A, Ya n g G W, Ka mat S, B or o k G M, Ga n d hi S, et al. Effect of 
r os u vastati n c o m pare d wit h ot her stati ns o n li pi d le vels a n d Nati o nal C h olester ol E d ucati o n 
Pr o gra m g oal attai n me nt f or l o w‐ de nsit y li p o pr otei n c h olester ol i n a us ual care setti n g. 
P har mac ot hera p y. 2 0 0 6; 2 6( 4): 4 6 9- 4 7 8. 
C he w et al 2 0 0 8 
C he w L D, Griffi n J M, Parti n M R, N o or bal o oc hi S, Grill J P, S n y der A, et al. Vali dati o n of 
scree ni n g q uesti o ns f or li mite d healt h literac y i n a lar ge V A o ut patie nt p o p ulati o n. J Ge n 
I nter n Me d. 2 0 0 8; 2 3: 5 6 1- 6.  
C o nt ois et al 2 0 1 1 
C o nt ois J H, War nic k G R, S ni der ma n A D. Relia bilit y of l o w -de nsit y li p o pr otei n c h olester ol, 
n o n- hi g h- de nsit y li p o pr otei n c h olester ol, a n d a p oli p o pr otei n B meas ure me nt. J Cli n Li pi d ol. 
2 0 1 1 J ul- A u g; 5( 4): 2 6 4- 7 2.  
D a vis et al 1 9 9 3 
Da vis T C, L o n g S W, Jac ks o n R H, Ma yea u x EJ, Ge or ge R B, M ur p h y P W, et al. Ra pi d 
esti mate of a d ult literac y i n me dici ne: a s h orte ne d scree ni n g i nstr u me nt. Fa mil y Me dici ne. 
1 9 9 3; 2 5( 6): 3 9 1- 3 9 5. 
F a b bri a n d M a g gi o ni 2 0 0 9 
Fa b bri G a n d Ma g gi o ni A P. Car di o vasc ular ris k re d ucti o n: w hat d o rece nt trials wit h 
r os u vastati n tell us? A d v T hera p y. 2 0 0 9; 2 6( 5): 4 6 9- 4 8 7.  
F o x et al 2 0 0 7 
F o x K M, Ga n d hi S K, O hsfel dt R L, Blasett o J W, Ba ys, H E. Effecti ve ness of r os u vastati n i n 
l o w-de nsit y l i p o pr otei n c h olester ol l o weri n g a n d Nati o nal C h olester ol E d ucati o n Pr o gra m 
A d ult Treat me nt Pa nel g ui deli ne III L D L‑ C g oal attai n me nt c o m pare d t o ot her stati ns a m o n g 
dia betes mellit us patie nts: a retr os pecti ve st u d y usi n g a n electr o nic me dical rec or ds datas et i n 
t he U nite d States. C urr Me d Res O pi n. 2 0 0 7; 2 3( 9): 2 1 2 5- 2 1 3 3. 
Gr u n d y et al 2 0 1 8 
Gr u n d y S M, St o ne NJ, Baile y A L, Bea m C, Birtc her K K, Bl u me nt hal R S, et al. 2 0 1 8 
A H A/ A C C/ A A C V P R/ A A P A/ A B C/ A C P M/ A D A/ A G S/ A P h A/ A S P C/ N L A/ P C N A g ui deli ne 
o n t he ma na ge me nt of bl o o d c h olester ol: a re p ort o n t he A merica n C olle ge of 

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Car di ol o g y/ A merica n Heart Ass ociati o n Tas k F orce o n Cli nical Practice G ui deli nes. 
Circ ulati o n. 2 0 1 8; 1 3 9( 2 5):e 1 0 8 2 -e 1 1 4 3. 
I nter n ati o n al C o nfere nce o n H ar m o niz ati o n of Tec h nic al Re q uire me nts of 
P h ar m ace utic a ls f or H u m a n Use 1 9 9 6 
I nter nati o nal C o nfere nce o n Har m o nizati o n of Tec h nical Re q uire me nts of P har mace uticals f or 
H u ma n Use. T o pic E 6 N ote f or G ui da nce o n G o o d Cli nical Practice: C o ns oli date d G ui deli ne, 
C P M P/I C H/ 1 3 5/ 9 5. 1 9 9 6. A vaila ble fr o m: 
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I Q VI A  
I Q VI A l o n git u di nal patie nt prescri pti o n data base ( L R x). 
M as o n et al 2 0 1 8 
Mas o n C, Katz marz y k P T. Varia bilit y i n waist circ u mfere nce meas ure me nts acc or di n g t o 
a nat o mic meas ure me nt site. O besit y ( Sil ve r S pri n g). 2 0 0 9 Se p; 1 7( 9): 1 7 8 9- 9 5. E p u b 2 0 0 9 A pr 
2. Errat u m i n: O besit y ( Sil ver S pri n g). 2 0 1 8 N o v; 2 6( 1 1): 1 8 1 5. 
Meli n et al 2 0 0 4 
Meli n J M, Str u ble W E, Ti p pi n g R T, Re y n ol ds J M, Vassil T C, Le v y SJ, et al. A c o ns u mer use 
st u d y of o ver-t he-c o u nter l o vastati n ( C U S T O M). A m J Car di ol. 2 0 0 4; 9 4: 1 2 4 3- 8.  
Merc a d o et al 2 0 1 5 
Merca d o C, De Si m o ne A K, O d o m E, Gilles pie C, A yala C, L o ustal ot F. Pre vale nce of 
c h olester ol treat me nt eli gi bilit y a n d me dicati o n use a m o n g a d ults – U nite d States, 2 0 0 5- 2 0 1 2. 
M or b M ortal W kl y Re p ort. 2 0 1 5; 6 4( 4 7): 1 3 0 5- 1 3 1 1. 
Olss o n et al 2 0 0 1 
Olss o n A G, Pears J, Mc Kellar J, Miza n J, Raza A. Effect of r os u vastati n o n l o w - de nsit y 
li p o pr otei n c h olester ol i n patie nts wit h h y perc h olester ole mia. A m J Car di ol. 2 0 0 1; 8 8: 5 0 4- 8. 
Pell o we et al 2 0 1 0 
Pell o we E, Sala k o K, S nelli n g S, Ur dai ba y C, West o n C. Dail y varia bilit y i n waist 
circ u mfere nce. Heart. 2 0 1 0 A pr; 9 6( 7): 5 5 0.  
Pfizer I nc 2 0 1 6  
Pfizer I nc. Act ual Use Trial of At or vastati n Calci u m 1 0 m g. 2 0 1 6. A vaila ble fr o m: 
htt ps://cli nicaltrials. g o v/ct 2/s h o w/res ults/ N C T 0 1 9 6 4 3 2 6. 
Ri d ker et al 2 0 0 8 
Ri d ker P M, Da niels o n E, F o nseca F A H, Ge nest J, G ott o A M, Kastelei n JJ P, et al f or t he 
J U PI T E R St u d y Gr o u p. R os u vastati n t o pre ve nt vasc ular e ve nts i n me n a n d w o me n wit h 
ele vate d C-reacti ve pr otei n. N E n gl J Me d. 2 0 0 8; 3 5 9: 2 1 9 5- 2 2 0 7.  

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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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Sc h ulz K F, Alt ma n D G, M o her D, f or t he C O N S O R T Gr o u p. C O N S O R T 2 0 1 0 State me nt: 
u p date d g ui deli nes f or re p orti n g parallel gr o u p ra n d o mise d trials. B MJ. 2 0 1 0; 3 4 0:c 3 3 2. 
U S F o o d a n d Dr u g A d mi nistr ati o n 1 9 9 0  
U S F o o d a n d Dr u g A d mi nistrati o n, Di visi o n of Meta b olic a n d E n d ocri ne Dr u g Pr o d ucts. 
G ui deli nes f or t he cli nical e val uati o n of li pi d -alteri n g a ge nts i n a d ults a n d c hil dre n. 1 9 9 0. 
A vaila ble fr o m: htt ps:// w w w.f da. g o v/ me dia/ 7 1 1 6 5/ d o w nl oa d ( Wit h dra w n). 
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U S F o o d a n d Dr u g A d mi nistrati o n, Ce nter f or Dr u g E val uati o n a n d Researc h. G ui da nce f or 
I n d ustr y – Self -Selecti o n St u dies f or N o n prescri pti o n Dr u g Pr o d ucts. 2 0 1 3. A vaila ble fr o m: 
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W orl d Me dic al Or g a niz ati o n 1 9 9 6  
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Y us uf et al 2 0 1 6 
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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C O N FI D E N TI A L A N D P R O P RI E T A R Y  
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Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 0  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 1  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 2  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 3  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 4  of 1 5 5  
 
C CI

Cli nical St u d y Pr ot oc ol  – v 8. 0  
Astra Ze neca  
5 m g R os u vastati n wit h a We b A p p ( C o m bi nati o n Pr o d uct)  - D 3 5 6 P L 0 0 0 1 5  
 
C O N FI D E N TI A L A N D P R O P RI E T A R Y  
1 5 5  of 1 5 5  
 
 
 
 
 
C CI