PUBD Training

8/17/2019 PUBD Training

1/57

Potentially Unblinding Data

(PUBD)

October/November, 2013


2/57

For Internal Use Only. Amgen Confiential. 2

PUBD - Overview

! Intro"ction! #o$ to recogni%e &U'(

! )t"y (oc"ments t*at ientify &U'(

! )O&s, +ANs an FO+s

! &rocesses

! oles

! &otentially Unblining events

- scalation an Notification

- Net )tes

- Conse"ences

! Aitional Information on &rocesses


3/57


PUBD – Introduction

In recent mont*s t*ere *ave been several otentially"nblining events, incl"ing

- &U'( files in "nrestricte folers folers not roerly restricte

or files lace on stanar folers4

- &otentially "nblining information in email to bline staff 5(+4

- )cramble ataset $it* otentially "nblining information

("e to t*e criticality of maintaining a blin for a st"y an

t*e negative imacts affecting everyone, t*is

resentation *as been constr"cte to reinforce roer

roce"res to revent eos"re to &U'(.


4/57


Consequences of unblinding - Data

integrity in question

! ose bline st"y team member may *ave to beremove from t*e trial

! An etreme case co"l be reg"latory a"t*orities

re7ecting ata "e to erceive bias "ring trial con"ct

! 8*ere is a %ero tolerance 9&I/)5A in lace $it* F)&venors

- +onetary conse"ences/enalty may be alie er signe :O


5/57

For Internal Use Only. Amgen Confiential. ;

!ow to "ecogni#e PUBD! &otentially Unblining (ata &U'(4 is any information or ata t*at is collecte "ring

t*e con"ct of an Amgen clinical trial an rior to initial loc< of t*e atabase $*ic*may

- Inicate or infer treatment assignment

- Create bias in t*e con"ct of a st"y

- Imact t*e integrity of t*e clinical trial or ata

! amles of "nblining ata incl"e

- 8reatment assignments

- Antiboy A'4 res"lts

- &*armaco


6/57

For Internal Use Only. Amgen Confiential. >

$tudy Docu%ents t&at Identify PUBD

! 8*e rotocol is t*e rimary so"rce for efining &U'( an timing fort*e "nblining of t*e ata an treatment assignments. 8*e follo$ing

oc"ments $ill ientify &U'( base on t*e rotocol

- ')+ &lan

- =):/(8&

- )O:/C*arter - ()8: - )): (ata Ac"isition tab

- C*ange Control :or


7/57For Internal Use Only. Amgen Confiential. @

$OPs' *s and +O"s! )O&?01B@B6 Foler Access &rovisioning &rocess

! )O&?01>1 Access to estricte (ata

! )O&?000>B6 (isclosing 8reatment Assignments for anomi%e Clinical 8rials

! +AN?001;@ evie$ of &otentially Unblining (ata

! +AN?001>1B Creation, Aroval D +aintenance of t*e 8rial Integrity (oc"ment

8I(4

! +AN?001>1 Accessing an (istrib"ting estricte (ata for Amgen Clinical 8rials

! FO+?0@2366 estricte or &otentially Unblining (ata &lan

! U+AN?0002@; an CE eternal file *anling4

! FO+?00B23> signoff form for "nblining of res"lt ata4

! +AN?000@2 an CE reorting, scrambling an )A) Cs4

! +AN?0010B0 CE lacement of signoff form for "nblining of res"lt ata4

! +AN?0010B2 an CE estriction set " in ave for &U'(4

! +AN?0010B6 an CE E"iance on &U'(, restrictions4


8/57For Internal Use Only. Amgen Confiential. B

$yste%s Processes ,&at ay !andle

PUBD! eort generation re"ests

- )crambling

- CA

- 55

- Any C( st"y reort re"est

- 8reatment assignments! ternal (ata

- 8ransfer to eternal gro"

- 5oas to C8('

- 8ransfer to C8)#A( for Non?C8(' or for "nbline gro" revie$

! it C*ec


9/57For Internal Use Only. Amgen Confiential.

$yste%s "ole aut&ori#ed for PUBD

&andling

! As a r"le, "ntil t*e atabase is formally "nbline, t*e follo$ing systems

roles may access treatment assignments limite to t*at re"ire to erform

t*eir role4

- 5ea &rogrammer

- C)I or 8ec*nical )ecialist

- (A/(I &rogrammer

- )A) &rogrammer

- C( &rogrammer

- )t"y (esigner


10/57For Internal Use Only. Amgen Confiential. 10

&en Potential Unblinding "is. Is

Identified – /scalation and *otification! Any E)O (+ 8A an )ystems incl"ing F)&s4 s*o"l notify t*e follo$ing oversig*t

roles immeiately $*en a otential "nblining ris< is ientifie

- )t"yGs Amgen &5, F)& Os 5ea, Amgen Os 5ea

! refer to the DM Systems ECS Portal for FSP and Amgen Ops Lead contacts

! refer to GMAT for Amgen PL of the impacted study

! Amgen Os lea, F)& Os 5ea an Amgen &5 $ill engage t*e reorter to establis*

initial ris< assessment confirming t*e reorte ris< is not a false alarm

! If it is not a false alarm, Amgen &5 $ill notify t*e follo$ing istrib"tion list immeiatelyan $it*in t*e same b"siness ay of ientifie incient $it* s"mmary etails an

rovie aily "ates "ntil t*e iss"e is close

$u%%ary details to be included Distribution 0ist

1. (escribe *o$ $as t*e ris< ientifie

2. (escribe t*e establis*e start time of eos"reof ris<3. Incl"e root ca"se if available6. Incl"e "nblining eos"re analysis if available;. Incl"e corrective actions an stat"s>. (escribe lanne net stes see net slie4

5ea (ata +anager

Amgen )r +anager5ea &rogrammer/C)I)ystems Oerations +anager 9im :a* 5o$4F)& Eovernance D Oversig*t 8ab #oa4(+ 58 ob 8arney/8ina #arris, 8aras Cariac4&U'( 58 sonsor 8ina #arris4&U'( )r. +anager )+ (avi +cErat*4Cc F)& Os 5ea, Amgen Os 5ea

F)& an Amgen Os 5eas contact information

https://collaboration.amgenpartners.com/sites/CDMSys-513171/default.aspxhttps://collaboration.amgenpartners.com/sites/CDMSys-513171/default.aspxhttps://collaboration.amgenpartners.com/sites/CDMSys-513171/default.aspxhttps://collaboration.amgenpartners.com/sites/CDMSys-513171/default.aspxhttps://collaboration.amgenpartners.com/sites/CDMSys-513171/default.aspx



&en Potential Unblinding "is. Is

Identified – *e1t $te2s! +$P3%gen O2s 0ead is res2onsible to ensure

- emove ata/o"t"ts immeiately ost acB6 - &er confirmation from Comliance, for confirme non?eose event, o not nee N8F



Overall Points to "e%e%ber3+ollow

&en !andling PUBD! IPO",*, lt&oug& users are able to create folders in C,$!"/D' only

%gen +$, Business Owners are allowed to create PUBD folders wit&a22ro2riate restrictions

! Al$ays verify t*e correct foler "ner t*e correct st"y rior to lacing &U'(.

! Al$ays c*ec< restrictions on t*e foler rior to lacing &U'(.

! Immeiately notify manager of any otentially "nblining event

! (atasets $it* &U'( ata incl"e t*e $ors HrsltG or Hres"ltG

! estricte foler names incl"e t*e $ors HblineG or HrestricteG

! Never "se ro"ction &U'( as test ata

- Uate $it* "mmy s"b7ects or "se entirely "mmy ata

! Never sen any atasets via email. Al$ays lace on cts*are an sen t*e cts*arefile lin< to t*e re"ester

! Never reference any etails on &U'( recors via email

! Al$ays revie$ email boy to ens"re t*ere in no &U' ata before for$aring or

resoning


13/57


14/57


$$ /dit C&ec.s

against C,DB or non-C,DB data

! Any testing s*o"l "se non &U'( ata eit*er "mmy or nonbline ro"ction ata4

! Confirm o"t"t location is acc"rate an t*e foler is restricte aroriately by man"ally

revie$ing t*e foler roerties

! &rogrammer to confirm restrictions rior to r"nning any c*ec


15/57

For Internal Use Only. Amgen Confiential. 1;

/1ternal Data! )O:/C*arter/etc

- =enor oc"ment secification s*o"l incl"e bline information

- Covance (+ $ill contact F)& (A Os 5ea if any ne$ )O:s rafts contain

bline information for revie$.

! 8*is revie$ is to verify t*at *anling of t*e bline ata is ac*ievable

! amle is for reeat or "nsc*e"le visits - as &U'( c*ec< r"n by (A cannot

iscriminate by certain "nsc*e"le or reeat visits, it is best to *ave all

"nsc*e"le/reeats as bline.

! (ata *anling - any aitional *anling of res"lts s*o"l be

incl"e in (8&/=):

- As is original bline file sent to reciient or lace in foler

- +as


16/57

For Internal Use Only. Amgen Confiential. 1>

/1ternal Data

! (A to eec"te "bc*< for all *eaer ata rior to loa into C8(' an non?ctb

ata files

- &"bc*< o"t"t $ill nee to be revie$e by (A an F)& Os lea to verify

&U'(

- (o not loa ata if any &U' ata fo"n in *eaer file

- (o not lace non?ctb ata files if any &U' ata fo"n in *eaer file

! 5oaing of &U'( ata to C8(' only after signe "nblining form i.e. FO+?

00B23>4 is receive an confirmation from 5(+ to loa &U'( ata. 8*is is tyically

$it*in 3 ays from Initial 5oc<

! Any lacement of &U'( ata on cts*are

- =erify ermissions of foler by man"ally revie$ing t*e foler roerties

- If foler oes not eist, re"est t*e Amgen FA)8 '"siness O$ners +ic


17/57

For Internal Use Only. Amgen Confiential. 1@

PUBD C&ec.er Pur2ose

! &"rose C*ec< if t*ere are any val"es in t*e any of t*ebline fiels in *eaer files receive from eternal

venor. 'line Fiels s*o"l be emty in *eaer tet

file

! Fre"ency "n &"b( C*ec


18/57

For Internal Use Only. Amgen Confiential. 1B

PUBD C&ec.er "equests

! (A eresentative $ill re"est &"b( c*ec< rogrambe set " for a st"y

! 8*e email incl"es )t"y J, =enor, Fiels $*ic* are to

be bline, =isits t*at s*o"l be bline

! mail also s*o"l *ave =): attac*e


19/57


PUBD C&ec.er Process

!Navigate to t*e at* /cm/ro"ct/st"yJ/lab

! =erify if "bc*ec< irectory eists. If not t*an create it.

- .g. /cm/amg16;/20001;B/lab/"bc*ec<

! C*ec< for rogram arams.sas in t*e foler

- If it oes not eist, coy it from /cts*are/cm/sas/general/scrits/an moify it accoring to t*e re"irements

! C*ec< for rogram for any artic"lar lab in t*e foler

- If it oesnGt eist, e.g. covancea@B;200>[email protected] coy from

/cts*are/cm/sas/general/scrits/

- &rogram Name laba an moify it accoring to t*enees of t*e c"rrent st"y. Name of t*e rogram s*o"l be

la!name aNNN studynum!er .sas, a samle coe belo$


20/57


PUBD C&ec.er Para%s4sas

! Contents of t*is coe1.(ata (irectory $*ere t*e =enor files are

locate

2.=enor Files!. 'asically, efining macro variables t*at *ol t*e val"es

of venor ata irectory an t*e filenames e.g. belo$


21/57


22/57


PUBD C&ec.er $et U2 Caller 2rogra%

contd4


23/57



contd4

! (atafilename C*emlab2 is ta


24/57



contd4

! (ata ste t*at creates err ataset, "se t*e setnameassigne in earlier ste $*ic* is cl2. 5ist all t*e fiels

"se in fiel list an criteria2, e.g. fieldnameMK K

! 8*e macro call "dump#err call s*o"l list atafilename

e.g. C*emlab24, )"b7i Cevent field_list


25/57


PUBD C&ec.er 5C $te2s

! Anot*er )A) &rogrammer $ill be assigne to =aliate t*e rogram

! =aliator navigates to t*e venorGs foler "ner

/cm/amg$$$ /study#num!er /lab/%endor

- .g. /cm/amg16;/20110233/lab/covance

! =aliator creates a rogram name Hvaliation initialsG, e.g.

HvaliationmsG


26/57


PUBD C&ec.er 5C $te2s Contd4

! =aliator coies files from lab ata foler to valiation foler t*at

$as create in earlier ste

! =aliator t*en in t*e valiation foler renames t*e files insie, e.g.

t*e c*aracters &O( or UA8 $ill be relace by &U'(=A5

! .g.

- a1>200@0;>1?&O(?CO=ANCIN('5UNI8?C#+5A'3?

FU55?2011AUE0;12602;.tt

would be c&anged toa1>200@0;>1?&U'(=A5?CO=ANCIN('5UNI8?C#+5A'3?

FU55?2011AUE0;12602;.tt

- C*anging t*e filename as mentione $ill eliminate

any ossibility of t*e file inavertently being loae


27/57


PUBD C&ec.er 5C ste2s contd4

! =aliator Oens files in valiation foler eit*er in celor any tet eitor

! nters ata into t*e fiels t*at are eecte to be

bline

! efer to =): for fiel attrib"tes s"c* asc*aracter/n"meric etc.

! If some visits are to be bline, ata s*o"l be entere

in a ro$ for at least one of t*ose tyes of visits

! )ave an close t*e files an "bc*ec


28/57


PUBD C&ec.er 5C $te2s Contd4

! On t*e UNI romt, enter comman &U'(C#C9! )ystem $ill romt for st"y n"mber an in"t file

location

! For valiation, in"t file location $ill be t*e valiation

foler

! &"b(c*ec


29/57


30/57


PubDC&ec.er Progra% to P"OD

! If t*e "bc*ec


31/57


! ave &"b( (ata

- #eaer (ata gets 5oae into A=

- &"b( ata oes not get loae into A= "ntil "nblining

of t*e st"y

! Non?C8(' &"b( (ata

- #eaer (ata $ill be coming from eternal venor

- If t*e *eaer ata is in 88tet4 format, it s*o"l be

converte to )A) atasetataset name format

nb1, $*ere enotes t*e tye of ata4 an t*e

ataset s*o"l be store in ))( foler of t*e st"y

$cra%bling PubD and !eader Data


32/57


! 8*e re"est to scramble ata comes from - C(+

- E)&

! If t*e &"b( secs are not rovie $it* t*e re"est, as<

for it.! &"b( secs are create by 'iostatistics/E)&. Ieally,

t*ey s*o"l resie in (+ 8eams

$cra%bling a.ing "equests


33/57


! ave ata/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ss

! es"lt Files

/cm/a%g678/Protocol9/lab/bsm

/cm/a%g678/Protocol9/lab/covance

/cm/a%g678/Protocol9/lab/mrl

$cra%bling $tandard +ile Directories


34/57


35/57


! traction /cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ss

! (isg"ise Assignment estricte4/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssa

! &"b( ata estricte4/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssbline

! )cramble ata/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssisg"ise

! )sa an ssbline, bot* nee to be restricte. C*ec< $it*

FA)8 aministrators +ic


36/57


! )tanar +acros Use are at/cts*are/cm/sas/general/rograms/macros

! +acro Calling &rograms at st"y level resie "ner/cts*are/a%g678/inication/Protocol9/cm/sas/ec/rograms/at

aisg"ise

$cra%bling Progra% Directory


37/57


! C*ec< if &at*s4 to es"lt Files are rovie! If not, re"est t*e at*s4 to res"lt files to C(+ or 5ab

Amin irectly

! Once $e *ave t*is "ate t*e calling rograms $it* t*e

ne$ lin< an files as alicable

! *ote A' an &9 es"lt files m"st be in CO format,

i.e. 8ab (elimite. If t*eyGre not rovie in CO format,

re"est it.

! *ote 5ab es"lt files are ie HPG elimite

$cra%bling "esult +iles ("ave)


38/57


! *ote A' an &9 es"lt 88tet4 files m"st be in&O( format, i.e. ie HPG elimite. If t*eyGre not in

&O( format, re"est it.

! 8*e res"lt ata$*ic* is in 88 format4 s*o"l t*en be

converte to )A) ataset. Use t*e conversionrogramsif not alreay eists, create t*e conversion

rogram as er =):4 to o t*e conversion

! *ote 5ab es"lt file $ill be in )A) format)A) ataset4

$cra%bling "esult +iles (*on-C,DB)


39/57


ave! tract elevant A= ata "sing C(+)2)A)

- .g. 5A', A', &9 etc.

- 8*is $ill etract t*e ata "ner Q../ata/ss

- C*ec< an confirm t*at ssbline an ssa bot* are

restricte.

Non?C8('

#eaer ata.g. nblab1, nbab1, nb


40/57


!If t*e rogram are not alreay set ", set it ". 8*is canbe one by coying vario"s rograms from ot*er st"y

an moifying it accoring to t*e nees

! &rograms resie "ner Q/rograms/ataisg"ise at

st"y level

Process (contd4)


41/57


! "n +a


42/57


! 8*is ata is store "ner

/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssbline

! =ario"s &rograms t*at create Unblining ata are

o ea'lineA'ave.sas

o ea'line&9ave.sas

o ea)ynarc'line.sas

o ea'line5ab.sas

! :*at t*is oes is eas t*e es"lt Files, merges $it* #eaer ata an

t*an creates t*e "nbline file $it* bline ata t*at is store "ner

ssbline $*ic* again is a restricte irectory

! O"t"ts from t*ese are e.g. lab", ab",


43/57


! 8*is ata is store "ner

/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssbline

! =ario"s &rograms t*at create Unblining ata are

o ea'linNONC8('Ab.sas

o ea'linNONC8('&


44/57


! Oen t*e relevant )A) 5og

! C*ec< if t*ere are any errors resent. If t*ere are any errors,

ossibility is t*at in t*e macro calls, $rong filenames or at*names

are given. 8*ere may be some ot*er reasons t*at nee to be

investigate if errors are "e to some ot*er reasons

! C*ec< for A58 message. A58) are resent in case of t*ere isany mismatc* of t*e ata, i.e. recor eists in res"lt files, b"t

corresoning recor oes not eist in *eaer file. .g.

A58 (ata from res"lts file oes not *ave a matc*ing *eaer recor

in 5A'A55 t10>>61001 Foler:6B )A)NA+A&O'

A58 (ata from res"lts file oes not *ave a matc*ing *eaer recor

in 5A'A55 t10>>61001 Foler:6B )A)NA+5(5(

$cra%bling 5C $te2 for Creating

Unblinding +ile

$cra%bling ,o "esolve is atc&es of


45/57


!Contact (A or ')+ as alicable, rovie t*ese alertsan re"est to c*ec< an get t*e "ate *eaer file.

)to rocessing t*e file t*at *as A58).

! For 5abs, only rovie t*e alert as in eamle above. (o

NO8 rovie =I)I8 (ate, =I)I8 (ate a$ or =isit 8ime.8*ese are act"ally resent in )A) 5og, b"t $*en

roviing t*e A58 to t*ese fiels nee to be ta


46/57


! )cramble ata resies "ner/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssisg"ise

! &rograms t*at create )cramble ata are

o +a


47/57


! )cramble ata resies "ner/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssisg"ise

! &rograms t*at create )cramble ata are

o+a


48/57


! N"mber of ecors in " an s*o"l matc*.

! C*ec< ata against &"b( secs. All variables er secs m"st be resent.

! C*ec< if t*ere is any restriction on n"mber of "ni"e s"b7ects in isg"ise ata

mentione in t*e )&C. If yes, t*e lin


49/57


! Any ata t*at is NO8 &"b( is consiere to be #eaer

(ata

! ntere into ave for ave st"ies

! For Non?C8(', t*e *eaer ata $ill be rovie by t*e

eternal venor

! At t*e en of t*e scrambling rocess, coy *eaer ata

e.g. 5abAll,nblab1for Non?C8('4 from ss to

ss*eaer.

$cra%bling !eader Data


50/57

For Internal Use Only. Amgen Confiential. ;0

! At t*e en of t*e rocess t*e follo$ing o"t"ts are eecte

7"st "sing labs for eamle4

! 5A'U or blab1"for Non?C8('4 &"b( (ata store in

ssbline

! 5A'( or blab1for Non?C8('4 )cramble (ata

store "ner ssisg"ise

! 8*en from ss irectory, 5A'A55 or nblab1for Non?

C8('4 coie over to ss*eaer

/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ss

*eaer

$cra%bling Out2uts in *uts&ell


51/57


! Fail"re to c*ec< )A) 5ogs of t*e relevant rograms

! Using $rong Files

! Use Coy an &aste, b"t forget to "ate t*e coe er secs

! +or labs in C,DB' %issing calculated $I values in t&e scra%bled out2ut

- In orer to calc"late t*e )I val"es, t*e analyte "nit an conversion factor from reorte "nit to )I "nit4 m"st

be set " in ave 5ab Amin mo"le for t*e analyte. In aition, t*e range secifically t*e *ig* range4 m"st

be assigne to t*e analyte for t*e lab venor "se for t*e st"y.

- "e%ediation

! If conversion factor is missing, 5(+ to confirm $it* 5( if t*ere is an available conversion factor. If so,

t*e conversion factor is to be arove an ae to t*e analyte in t*e ave 5ab Amin +o"le. If no

conversion factor is available, )I val"e cannot be rovie in t*e scramble ataset - only reorte

val"es

! If only t*e range is missing, 5(+ to confirm $it* 5( if tetboo< ranges are available for "se in t*e

st"y. If available, 5(+ to re"est to "ate ranges for t*e st"y. If not available, 5(+ to re"est "mmy

ranges to be "se i.e. 0?4. Note, t*e "mmy range selecte s*o"l be s"c* t*at none of t*e res"ltsare falsely flagge as abnormally lo$ or *ig*.

$cra%bling Co%%on Issues


52/57


! Create a ate foler, e.g. October2012 "ner eac* ssbline, ssisg"ise

an ss*eaer, eening on $*en t*e ata is re"este

! +ove all "nbline/&"b( ata from ssbline irectory to t*e +ont*year foler

create "ner it.

.g. +ove :u files from /cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssbline

to /cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssbline/+ont*Rear

! +ove all )cramble (ata from ssisg"ise to t*e +ont*year foler create "ner

it.

.g. +ove :d files from /cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssisg"ise

to /cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ssisg"ise/+ont*Rear

*O,/ ,&e $0 to 2rocess PubD is ; Business Days4 In case of *ew studies t&at need t&is set u2' it %ayta.e a day or two additional4

$cra%bling +inal $te2s


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! #eaer (ata "ner ss irectory to be CO&I( over

from ss to ss*eaer/+ont*Rear

.g.

COP7 :all filesrelate to t*e ata being scramble4

from/cts*are/a%g678/inication/Protocol9/cm/sas/ec/a

ta/ss

to

/cts*are/a%g678/inication/Protocol9/cm/sas/ec/ata/ss*eaer/+ont*Rear

$cra%bling Co2y !eader Data

$cra%bling $ending 0in.s to t&e


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! 8*e email *aving t*e re"est to scramble ata may

*ave information on $*o to sen t*e lin


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For Internal Use Only. Amgen Confiential. ;;

! Once t*e ata *as been rocesse an all stes CGe,

sen t*e ata manager an bline E)& rogrammer

lin


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For Internal Use Only. Amgen Confiential. ;>

! )en t*e lin


57/57

$cra%bling $a%2le PubD s2ecs

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