AsSMA

Date
Page
03-03 2022

linical Tuas
Blindud study2 maurlam sOmodemzauen
a:dm Uals Ae Yallimb au gvem Nlacebe
akjillb alHNde
30.0322

KPuu lwelohmenTsA Lenynlen Amd lenglhy

puts hal can lak1 uplo /5yans o l a
Mngli auug pta cot thatanay ealh ins a
mlens US Mollars. hough, u sheala"
ont eÁ Lhat tihis is a hiL,2onpeltie
noluubq on lhe ntvnaionbl velhva are
o Mamras _h1 pkugcelopnt wcec
Thal occwrs staenually
) scovy amd lecue
i)Pu-clikeal sluduis
iil) Chinical stuouts

scoery eson hi mocusstardousedh

uscove muw COmpouuma omuwpOunlal
yplwalet oMm n n g Lempound. nhe
AM Lmuw tmnounc hiial Amve tiying

hi acrly
efa compocnd
Aolubon

Basudom Adugala fUsuld, hi dcisnem á maok

On dNcletminl hu brug. Basedl on the
leciien, lh putes LNlevs Yhu rt-oluniéal
Bucly Q tminabd

lencalsudis Jn the oce-clnical stage

i)
 the xnilal loricology f Xhe Lnypound is
sludidon Anmals hilal fovmalotm of
he oug lvelotmen Andlspocili o
OmeNrsue hhavmacologncAl Audis au
aye wfomed kn ha saee on pnumcls. d
Ahe indhAhia sloge, Zhueknodnce of4dintual
salty akd stecluehin AAhu ougaaBd
movMedivrlh uasenabh Lrdmcehat
hi cruQ dloagewill mo &lalaland com
Aolvuded lajhumans

i)Luueal sucuisd hu pont Ahvu urdk

r t i e lss douon amiimas andAhu
Shudis havt Muggesud Ahal hera is áullcn
LNmdenet hal tHAug.uwill kfthu Sfl_
l o hwman suGjets. Aung hedtgn
human suljecls hbs 3phaswsashuch ome

ha1 hipwpoK ALPhasx1 kual i e

Lsalthh ht sinuual 'kalehy Amkomaken b
he lhetaf hi druglet huknans nuch
he Hangaceynialli longu and_Zhe
phatndookumetes efAluAebg. Ihse Auds
t MOmallyconotuotedn halhy human
wuntes. Jhd AO ANa Mmany AbrLourrr

lrzects Ais Ltveen 4 To 20 pvAhuelp

AOTh Aynlo 100Aulesjcets zjn totalovn hi
LEOG han tials
ha 2 The Phas 2 ueliis Qra clvacid tau
falurita nuhe ueill pnuall emet fpom a
 aeoNccug en lecleve Llosages and iniual
llects Yht coatG Lessiol lhlo severral
hndliAnalorns e AsUally selected or ha
dduenál conpleecleons lokid,cenfounderng
dactons

. has 3-?has3 studes jcovde essmemt

Aalely. lfecaey n nlumum dosage,hee
stiudio a Kesgrtduilh conbrols anc
Seatmemi o t s , L len AcOnnsing huundseds
Ao thaahds
SUMas Ooainid om Ahw udlies, e
4yucaluon koilll nlmtud lo the
Áthoiugeng authoutyl yovermmend instluóns
ke FDA, TéMR and oA) e sevriw f1anek
Ahe govenmen(lhouhis ge heraugh
VNDAY Newdrtug dyluealin),kn tu eloung
AUamitvs:
DMedicint iv) humistuy
in) heomacdogg Vtatistie,0
i Brenhwmateidees.
Och mevev may seqAwst LoA meru Lnomaluom

h tonpany zolalia ko NDA AeloruKakmiterg

Aullin sluriur o hu culhodnngaialhorily
06-04 22
o Marcket gclvity
nee a neuw ceuuqpypbcalhen (NDA)salmltd
e the aiho la ailhouly, menolunal
Aclstis. oilcems MRMarkh amalysis and
hollow-n AudhiA A Lamint he onq- m
Uki takW Ahe jomof cunical ials md a u
PCelersud to ayhar 5sucuis.
 hesM Aludus Ao e n
hu mam /uuyres
hot althu olanks a a t ky h1 Compa
gcbrlanvbt.|
About ih1 uw duug cam b

iemoluoril puwypesG ueyoilucl adyen

BempamymdAn sOmeOB Lh u gme.
mucd toBwlhcuaun duOm lhe marhel.
lviani uponioiis
he Slaluian oliarby lays anLmpotlan
Hol Lhuoughoul hi elbuddvelermntie
AomL Mmbng hia KUspehsiklTies hat cuu
fuotiol 4atstóianí n phaemauilial
indusbs e intud elos
ioteyiaksn Ihe leekemnt planef he
ludy en dug
inducldsgn hnd puotocol doeleyameni:
iit)eveepung"amdominauon sehomea
i) alss lam Dnd pueqram Auelepment
HyioatAtporalion wilh yuepuali kalda
nd Nual HyvwAlalion
vi) nugrah plnical sudyKele, alply ana
eacy Oulls.
VII muhucalion k dulnce NDA Lo n
uilhousng Huwut anet.
VIt) lwauon suyyert and consullalon Aulh
Pih Copany fUsONnel
hiapculic uiab
y a Lempaaue rinls
lal Qum al hiy Ondomyi
2omparung asamdard uar
 he innévalve ocalment As bcTlr han M
standand M n .leumi a} Cuney amd
Tolnnc

xonhylaclc Muals
hiy re fuevenlave uala hal dlforuom
olv clenucal vala as luq.
huallhy sMeojecls t Mdyeols ckydilul
hemk ueas ualthu
26O4 2
Lenal Pmeyles fhuayuuae ugl
She olloaung ava gnvalfuunciplbs lo
ovkvrol infilannlng nd coneiucleng a goo
slud
i)Corufllomuulalon af he qpasuons for whurk
uckseamswes AMNauwud
i&cson on lhe mojt apuepual oms
tias(conbols), fruefpcally lo jlkdy
COncwounly
ni) hu essence a conbolud biols lhal pa
COnpanolk sludy muyl bemad higmw
átmenl shoulett pomnawdmlh a
hatmacdogically bnued Auyanalion lo ehech
chetheor Hoa a y yrucinoh efeol on he
hneas
w)otlecluonel paluims for ricleson pin he bial
bcleru A h r o n hs lo Ashioh bualmnt
oyn hey uvill eAnelucled ik: q1aluink shosdd
OCe alloted Jo lht Aruals al nanddem
heneuen frendbu Jon subjicuive enaluahn,
uals shouled e. aordnged that neilheu t
hyscon me ih Youent,knocs Lohuch
 amwlvwd Ths s u .
ualmeml As bnq m d Ayslum o n l .
knaenas Aoult
hifoOON ANO mg
n d and Avhen
buned, hm t d L
dalo s abo ky
ujnh dmd'syiern:
deéMOn On htmcua and m hed ofnah
vi) abverahohs o n l
systnalhc amcd tvilnent
awaulal
fratuntaAO Ahal ulwanl dala u
n a l y s Ol hu snd.f ual alemgwilh
vi) cmensn he pecedush 4
ond dovalns pvenW hicosign
utlhonowah
hal ows Ahvung h1 buials
dhnens ON ddla fuocimurq Alalhral
vi) h
pdnchunon
AMalysaAnd on awvmg
Lirlertnces

bualmnl
hiams o pllocal sulbjicthlo lh hat
lucha way
md conbuol qrouns Am in all
h o y n Du Lmiially sGuNatr
Rsptels tliwani lo he prauvy.
alon yem ingn
X
o hecvratonsom he
Suluauomd eaduna
LOntmen
U NOT
AUOCLlwus KauolHown
uch
Auuing he tcuon Adeigns

he patints have been inclids yn Ahe vetk.

hollauvag
d hunapy has kon daniud hu Ausuluing
0 Sorn m m e n Aulualuons
Umowad elnaluintapemhe sluay:
Sakal side eeis
ii).Jeloruoluon"of sulgecu pondilion
 itt)rath duu Jo lhur kauses
iv)Aack ALONUnallen hcom sdeyeclo
o s Ko Lolou y
The abovt levmauons mut k conniolvaod sm {hu
salusleal analyns Mmd, Arlvunces muul L
Satsle

made akmg decouml of heye dnaluons,

30.042
XBanucuntylto lnepbylacui uala
Jhi oanC ULncf lts
Smilar le lhei Khurfuluc ials
we uys AM Mhbhed alk1 s lar s
ondok, acyl hal onu AA qNm Aukjphalarki
andiht olht is o t Jhue oups owu len

foluclid AIYn has nlfvad a lower

yuoctid.

ht sugnilcant Alkvnce luueer fuokuylaclu

Oncd hdeapoulic uak.s ht scalh M
Aicls Jhi puepnoclen ef Hhepepul&ton
lukly o be allackud Hy a 4iecise dsas
uGAUy small dine, uNaless hu Auwo ys
An htuialon langg Ahuu willnot Le
Woviele slandard meamun againkst he

ha ayueta cembrela dergn amd amauysis

Q homdak lo hes in Anapudnc tikálo.
longe Mak ld ual ca rienhylaclc
Tiolots andliyense urclituch bualb
Lull k OuÄ Jaanluculany4m
Aecluouoseaes (Cortiaguous secses)
xncwaluonal Auelis
hly anteLlen Lonentdwnlh iobnukyng

Lenauluen LLUlh Milvmnihg piit

Uhclo lcome pnAalwNis Leha

n Theme eamm KuwalonalAudis Ae

LLhaLMOK- ACluonal oAongAludonal:Th
JHeHuclue nd suooyuclit Aludais
ywmmlalSudis pA MOu Lllhcinl m
myoNng caual AtalienshyjlleatJahial
ie Lhickl MonAidaiens imit hevr ss
Naduonal Aiuolis on hu elhuuhand ana
me LAiClh LeLNaluati duiase -sisk aete
RACkaions dpui Zhiin fpoimual fg

h AOntblling sukual dhsleuingl hcton

hvus uM dovdalenal Auuciis.1k toe to

XHoA-SLCluenal Muchi
uoN-sUCuonal sudy does mot take he
Umyoal ulatuonsh kUem hu faco
saudliolmle accAmi: Mually MAhwewes
he Lnammaluon LaAOISAlon l a
Aranlilan epulhtiom at mLpaviudulan
Ontam : HON:MAonal jtuoliis masy
L bastd on uandom sanmplu jema V
dlnicdJropulalm LOna putésnlio
Abmryli o paltml stlh a fianiiaular
 AmYnlenLd AO uchy aYVOOon khwn
ulennt dsaslconduuóns; houever luy
CAhnolLn addvminu whuch doass
mghi{
htin ccwvd fust
06-0522
4 n tms afennlainingdiion ymoloqy,
buy vuovtole eny liilited inlohatiorl h2
uNalma a diseas tan bececdli
dned AA AhiJbporluon of humans uhe
hbve th Oiat

*omludundlsluchis-
i oyauclive sudis s Ale knoun asu
Ochwt Audiis;Ancidce gOllcw u
studuis: hvu ouLus kqyssudhis kosed
i)ymeleqcal sucy2hou ni Alarts
Aslhamimiually2hallhy 2hud o
Amadcualakapoud te fownt
lvclse suyiofid suskhtclor pa
Causluhe au ollocdtim to
llvmure he kibegwm mcidene
ii)Ploqnesuisud huu patim uth
astucc disal Jolloud yn ig9
dlontint utiuehaers pelatu to
husn morlaalhiis gmolaliy

putena Aemplief poutnts

wrlh aouion nd hl'patuins de
Mont sm caltndan um kaut olin
 foAKUcesul anayus th dato cdllui
OpuWmins AQu mbTFAmyórlant

HApOnA AUndAuoy G: A Qencl

Alwnce sUponA Ah sAoal sldiis
i)kepollav uh must be LOmpliid alla
U a n y , s metseholaw- yn Lmun
diicemflhe azhich awll allect le
wauddy A conclusions dicltn castdon
kenultsida lang LAtnt
40522
AUhen Ahi data is An the fem dwenls, Ahi
slunglh of ceeulalon eloeh Ihe ruik faedo
Andh man mayktAapiendALKLÉhie
HK LULnud As iRR Anlma ef clussau amerg
Amcdma of YaM Amorg
suntposLd
h Uulto puAuisn io An a 2x2 (alte
pDeva Pusmnt Absent
b
No d
Thim ulauve uuk Lank Chkmd as:
RR: ACd
bc

Fom mot Ausas,

As HULalwey tanlXhiDCumnci
Lveni mw CAKs
suuoy. Landy mume Ihus sn a tohurt
study nlelyeca mty
ra lo samumid
Latrposkru salus ak
olloved- uphoALong bmt fo oblain
mullucwnt nuhbeAcdss Such a suudy u
muhurYacal rkr Aaside hu ubelom
em aMmpli o ucypopulalon yokh
ham mclucimd hi erlin ouulauen

inguushid AMW Kelwnca 6 myppoud lo

t elc uin Lach gudp, uhuuas im'

lrbkpnche sudyhu gyoupa Ahurtid
udu ane Achovn l h pielpnmaA lo h
tluct hhclviduals nottahiklng sueh ipc
Jhs"shlh
AlAhen hoa LLompanauie indy
fUOpectve Audy gosLowwnd Lom pik-
actor to civeloqlmukt he ihd povnt
ntwstnd thiMdosfpobie ptucl Mar
olh smdpoumt&moe oask sm Emu ko
Ademlily he sk Laclior. Gn riiuoyuehie he
Mucly n alimpAT isMaclh Je sompann
allcliolzlen uwih Mmi nn- ctho
mmiad of
oun umh pepulaten Ao hvu
Youu melaur yisk, only Am Lilunalid
Compuid AAoUous
Odcs HAio=Cadds that Lnpoud unduridual
a s had nen-ApOLd mdi

ORa/c aC
b/d bc
OR alse ulpud to as Kisk pdA 2oti
xkauéackse ulueyuclieAtudy
aelirumbralon elypefulalidn Lom uhuet
i)h oiuoial slih m ht
hfauuns com hs
g n ef PUbropecln sluue.
AKAJECaUilakir Aamp ef nefulaom A
A4CL Amporlamt dmy mllakes Ommulecl
ct
AhiS sla wil Amtusuuce bas mi he

elaubnskaja
here t 3 milhcds for choevinq pontuol
LOYNA:
)Pamadem Aamnlug
i pcknuaui f mmaWhung
alumb' wh Ahvl cleoses
x onkcdenc gnluNal Lou OddsRalu
as'un thu cak eLsouynue slausuos OR
alse subyecl Ad Anplarq wue: hu
landand
oplLa
6 E(OR)=ORx t+
ab
Thsas waid ndvn
al Alandand näaken m 2x21
Mowenackl
Auhn Íhe matwnd Wolt milha can bt usd
LOnmdvud to kmdLeghrutihm
SE(OR). e
el OR A%
EOR9=
5 E(n OB
951 l
nonicnce L kn OR Can ke
LKOR 146 SElkn sttained q
OR)
 hi Amtewal islunmatus el OR au dvwcd as
Knliloq Aabove ctnhdena bmis.
05: 2

Measws AL Olmial mpact

Cna a cakse &LLluct uelaonshyjn belveen he
lsasO h elaled otconmu anol
LOAOUl o hu misk aclonhaNt beem
stablishud, a fuw Ahles Lam &Lompulid:
idtakaidalk KUk -> hs is alO knorn as siisk
mc all lllma: celnu he
LEA PEisk ef OieasZhal came lasceibed to
Nownt he Misk hoclo. Wer amd above
yond dence, itpeuatidespn suinai of te
miumber,A s of The clisea hat can be
UNmtd LryiwU Jo ukLaclon was
LUminalid.
AR 4mciolence eCuOK meng hos
Lposcl Jncauneu e aN amen
Ahox not LnpeKa
iorulatuontnibtaba Rsk -> hs as amwanue
LECAN PUsk olchsan AnArrunlaiuen Ahat
a n t solly dibilulad To thi stisk kocdor
Olainudby gmulirlyinq atuilkdali siisk
(AR)y pwhlemu Al pdwe o he srisk
aclo vlh ht frehdlaton:
indtilodalbapachon in expovd s aso
mamn asVauolone acluom M AXLeIA
AFE= RRLTV
RR
Aehvu KR As Hat meng honc anoid
 iv) lnulalde fpackuon m Kolal puulalon
hsss ahe Hnewrn as Tolal lelidogie facs.
hpUeporlhonef tal sisk d a
AMANOfuulblen hd cam br allrubrlid
LRYohuie To hu 4uspeclrd 4ish aclo
AFT: PlE1(RR-D
1 +PLE+](RR-D
Ahoe PLE=eporn pueplk nhe

isk ador
And RK-T)= once m hi Ancidine ef
ssay leluveek pteplk usheadLYOd
le Thi pisk Lactornd Kfhox Lché A nt

V)No.udidKe Lal> i s Ameaningkk avoy

AYvunng he komil nOciptje
loualment bvet A cenbsel gAen can be
Zhvrapuulic luálb makuidh meducal
Acnen Alvut palim.GnauàLlhat
CompaKB A Mew LLalmnt wlha stmdand
n number nedud to Tuai (NNT)gwes the
Mumalud umb epauenh ahg lewd o
aticl jolh Ah Muw Teamanl pAthv Zhan
Omaland ont. NNT Zhi imoK Aalsolul
pisk puducuon (ik hu Anne Xwem he
peehonluon ema n oenbrdl grtey
CP amd h pueporueneevenh n
uAmnt gruain (e),y hu
NNT B L
Pe-P
kg: e- - 20thm NNT: 10
pihuch means thiouatimont uwold Leod o Tu
 AaNTNG Lahunt loeveny 10 palunt
A Karsa buatment c t bts to sPmall NNT
amd ho lualmeni ct loadsto NNT eeing
Nuy KngA NN7 caN"also le uqullen ass
NNT Px RR

he 95corldma Lnowale NINT sqwn ey

1/R-PY:1.96 5E(R-
whuu SE (-R) :R(1R)+ P(1-R)
N
nlucalons A Beea hSUm MAivmnm
Lageylt ioacy
n hal nucéll tih dlhniuon &condiuenal
uItalltu PC/s) PAOB)
PCG
Lemvrdmulunluialion scule:
PAB) P(6). P(A/B)

23-05: 22 P(AB) P(A). P(B/A)

Bays huoewm has kum mau o n md Äo
wdluuai hufpunlemamce afhiagnoi &
Kminq i i , s i n g ahuw t t kegns

sulpechs knatto hasd helplierdi o t

Aeas miusi ing am ACYlid
ulpnend kmown as Andand lut.

A us dnou suljls notth a dosiias as D*

Rncd thojt wlhéul a duas a s D. Lutheer
Xhe muu Auagnostë ustasT Amd Ahof
mgale as tThalabte ef slejgek ave
Aauo CLomg o dsÅA Slatus and
Testend
 D D Otal
T a b a+b
TC d C+ d
kaa

Zhe Lellouing Chanacilhos a_

iSenitivly- his s hu fuuebablAhat
adisiae incldual iell Mave hat
Yapesl.
AKMSull and hnd callid uLL pel
kUal (TPR the Tet itTPR= P[TID
TPK a
a+C

dsas- indiniclual wtll hat ntgain

Hate TNR) h tis. VTNR: PITlD) 0
TNR= d
b+d
mfalbe Negatie Rat
(FNR)>Puebabrlt that|
LMmls il. FNR= PETID*)=
iJal Foviie Rati 0+C
(FPR)-Phoballty thata.
Tet uokIt ie. EPR= P(T+/1)=
b+d
v)uddie Naleuu loMie Pue6alalty
mmciNudual Alh that
Ahas n dneaM. J jeylve Zist JAnitt
Ole Rmown a
TouoYuotallty
Ascas: it. P(pt T*)=a Wstma
vi) edie Nalu a+b
migalie Pudsablty hal
mAmclNchual uAh gnegaluve i uT1
 does mol have Xhe clsase
PVN: P(D"IT):d
ultihd sfrernis lAhe wfomamcl a
Aemlv1ly Amd ecticl, AUll as Aan
sumat O_styvbaaclNe Nalue loa
rasdnculdr study. hi Jnhyuoam huho wthis

lung must tak1inlo _ccouml helecl

Any ladiwnces aJuo h Sudy amd acle
opulaklen on Ah pucielil ablly elAh
tist
cwrnoualor hanacvyiclwe-
efw Asilwrly Md sppciucdy rnayhutally
Auch a datam ai knbwn aROC cwwd.
pueyidus hs aMmylh Teool Yylyung
HUcluelve Nalhu mhood To lechoicdl
noilwy iliu.Ihas wNe As COnbhchd
y yldihg AhuTPR agavmst FPR.hu ROC
NeA CaM KeAUMd AEcompaL 2 iaqnotic
hi owtall necwacy sf hi
tut larGen hu
Aea mlvu theeel ktn he tei.
PVP and PVN can alye ke
the Bayes Rulh as alcaloud inq
Lolays:
.PYP P(D).P(T:|D')
P(D) P(T+ID*) P(D)P(T*|D)
+
uh P(D')7 Pwalmeu
P(D) P(TID)-enait
|-Pruvaluncu PTID)>|-enidlt