Transcript klinikuri kvlevis dizaini

klinikuri kvlevebis dizaini
kikviZe marina
Tbilisi, tfdec
2010
mizani
klinikuri kvlevebis dizainis ZiriTadi variantebis
analizi
kvlevebis sxvadasxva saxis gegmis susti da
Zlieri mxareebis aRwera
kvlevis dagegmvis stadiaze gaweuli didi gulisxmeva
da Sroma saSualebas mogvcems kvlevis Catarebisas
Tavi avaridoT potenciur Secdomebs da TvalnaTvliv
davinaxoT mimarTuleba Sedegebis srulyofili
analizisaTvis.
klinikuri kvlevebis dizaini
klinikuri kvlevis dizaini warmoadgens kvlevis
Catarebis gegmas.
konkretuli klinikuri kvlevis dizaini
ganpirobebulia imaze, Tu ra mizani daisaxa
mkvlevarma.
kiTxvebi, romlebic gansazRraven kvlevis
dizains
ra mizniT tardeba kvleva?
rogoria hipoTezis formulireba?
ra mniSvneloba aqvs hipoTezas?
- problemas aqvs samecniero mniSvneloba?
- problemas aqvs klinikuri mniSvneloba?
rogori formulireba unda mivceT kvlevis mizans, rom
davamtkicoT an uarvyoT hipoTeza?
kvlevis romeli gegma ufro metad Seesatyviseba dasaxuli miznis
miRwevas?
klinikuri kvlevebis klasifikacia
klinikuri kvlevebi
observaciuli
aRwerilobiTi
eqsperimentuli
analitikuri
klinikuri cdebi
/Clinical trials
SemTxvevebis
aRwera/Case reports
«SemTxvevakontroli» /Case-
SemTxvevaTa
seriebis kvleva/Case
control study
series
/Cohort study
erTmomentiani
kvleva
gamokiTxvebi
kohortuli
meta-analizi
/Meta-analysis
«SemTxveva-kontroli» kvlevis sqema
riskis faqtoris eqspozicia
daavadeba
+
+ sakvlevi
jgufi
+
_ sakontrolo jgufi
dro
monacemTa Segroveba
kvleva «SemTxveva-kontroli»
*Subjects with disease (cases) –avadmyofebi(SemTxvevebi) ,Subjects without disease (controls)
– janmrTelebi(kontroli), Exposed – ganicades zegavlena, Not Exposed – ar ganicades
zegavlena.
kohortuli kvlevis sqema
daavadeba
eqsponirebuli riskis faqtorisadmi
riskis
populacia
dro
ar eqsponirebuli riskis faqtorisadmi
+
+
-
kohortuli kvleva
*Population –populacia, Disease –daavadeba aria, Without disease – daavadeba ar aris,
Exposed –ganicades zegavlena, Not exposed –ar ganicades zegavlena,
«SemTxveva-kontrolisa» da kohortuli
kvlevebis Sedareba
«SemTxveva-kontroli»
retrospeqtiuli
kriteriumi:
Sansebis Tanafardoba
dabali Rirebuleba
sakvlev pirTa naklebi
raodenoba
efeqti → mizezi
kohortuli
prospeqtiuli
kriteriumi:
SedarebiTi riski
maRali Rirebuleba
sakvlev pirTa meti
raodenoba
mizezi → efeqti
Sansebis Tanafardoba
Ddamoukidebeli
cvladi
daavadeba
aris
ar aris
sul
zemoqmedeba
riskis faqtorze
a
b
a+b
uaryofiTi
zemoqmedeba
riskis faqtorze
c
d
c +d
sul
a+c
b+d
a+b+c +d
Sansebis Tanafardoba = a х d
(Odds Ratio, OR)
bхc
SedarebiTi riski
daavadeba
sul
aris
Aar aris
Mmoqmedeba
riskis faqtorze
a
b
a+b
Nnegatiuri
Mmoqmedeba
riskis faqtorze
c
d
c+d
SedarebiTi riski
(Relative Risk,RR)
= a(a + b)
c(c + d)
kvlevis dizaini damokidebulia Semdeg
faqtorebze:
sakontrolo jgufi (Control group)
randomizacia (Randomization)
dabrmaveba (Blinding)
kvlevis struqtura (Trial format)
klinikuri fenotipis gansazRvra (Clinical
sazRvrebi (Endpoints)
Phenotyping
)
kontrolis saxeebi
placebo-kontroli

pacienTa erTi an ramdenime jgufis, romlebsac utardebaT
mkurnaloba Sedareba pacienTa jgufTan, romlebic iReben
placebos.
aqtiuri mkurnaloba

pacienTa erTi an ramdenime jgufis Sedareba, romlebic iReben
sxvadasxva preparatebs.
istoriuli kontroli

mimdinare kvlevis Sedegebis Sedareba warsulSi Catarebuli
msgavsi kvlevebis SedegebTan.
kontrolis saxeebi
kontroli mkurnalobis gareSe

pacienTa ori jgufis Sedareba, romelTagan
iRebs mkurnalobas.
mxolod erTi jgufi
gamoyenebuli dozebis Sedareba paralelur
kontrolSi

pacienTa jgufebis Sedareba, romlebic iReben erT preparats
sxvadasxva dozebSi.
randomizacia



iZleva garantias, rom avadmyofTa ganawileba
jgufebSi iqneba SemTxveviTi da masze ar
imoqmedebs arc mkvlevaris subieqtivizmi da arc
sistemuri Secdoma.
qmnis statistikuri analizis Catarebis safuZvels
samkurnalo efeqtis monacemTa raodenobrivi
SefasebisaTvis.
brma meTodTan erTobliobaSi saSualebas iZleva Tavi
avaridoT avadmyofTa arCevisa da mkurnalobis
daniSvnasTan dakavSirebul sistemur Secdomebs.
randomizaciis meTodebi
martivi randomizacia
– kvlevis Sesadarebel jgufebSi monawileTa SemTxveviTi
ganawilebis wesi (mag., SemTxveviTi ricxvebis tabulis
gamoyenebiT).
randomizacia blokebs SigniT
– kvlevaSi CarTuli pacientebis saerTo raodenobidan
yalibdeba blokebi TiToeulSi pacienTa luwi ricxviT.
– TiToeuli blokis SigniT naxevar pacientebs eZlevaT
mkurnaloba a, meore naxevars ki – b.
stratifikacia
– pacientebis randomizacia dafuZnebulia faqtorze, romelic,
rogorc varaudoben, zegavlenas axdens kvlevis Sedegebze
(mag., bavSTa asaki).
dabrmaveba
Ria kvleva
_ mkvlevarmac da pacientmac ician, Tu ra mkurnaloba
tardeba.
martivi brma meTodi
_ mkvlevarma icis, xolo pacientma – ara, ra saxis
mkurnaloba tardeba (Zalze iSviaTad - piriqiT).
ormagi brma meTodi
_ arc mkvlevarma, arc pacientma ar ician, ra saxis Careva
tardeba
kvlevebis struqtura
ganixileba klinikuri kvlevebis dizainis 3 ZiriTadi
varianti :
klinikuri kvleva erT jgufSi (single group design)
klinikuri kvleva paralelur jgufebSi (parallel group design)
- faqtoruli modeli
- araerTgvarovani modeli
klinikuri kvleva “jvaredin” modelSi (crossover group
design)
klinikuri kvlevebi erT jgufSi
klinikuri kvlevis Catarebisas erT jgufSi yvela
pacienti iRebs erTi da igive eqsperimentul
mkurnalobas.
kvlevis es modeli gulisxmobs mkurnalobis
Sedegebis Sedarebas sawyiss
mdgomareobasTan. Sesabamisad,
randomizacia am dros ar tardeba.
klinikuri kvlevebi erT jgufSi
klinikuri kvleva modeli erT jgufSi SeiZleba
gamovsaxoT:
skriningi _ CarTva _ sawyisi mdgomareoba _
mkurnaloba _ gamosavali
klinikuri kvlevebi erT jgufSi
uaryofiTi mxare:
Sedarebis jgufis ar arseboba. Sesabamisad,
ver xerxdeba aqsperimentuli mkurnalobis
efeqtebis diferencireba sxva cvladebis
efeqtebisagan.
klinikuri kvlevebi paralelur jgufebSi
klinikuri kvlevebis Catarebisas paralelur jgufebSi
sxvadasxva jgufis pacientebs eniSnebaT
gansxvavebuli mkurnaloba.
statistikuri sarwmunoebis misaRwevad (sistematikuri
Secdomebis gamosaricxavad), am modelis dros
tardeba randomizacia.
klinikuri kvlevebi paralelur jgufebSi
randomizacia
sakvlevi pirebi
mkurnaloba a
mkurnaloba b
Sedegebis
Sefaseba
klinikuri kvlevebi paralelur jgufebSi
*Population –populacia, Assessment –gamokvleva, Eligible and willing subjects – Sesatyvisi
monawileobaze Tanaxma pacientebi, Randomisation –randomizacia, Test –sacdeli
mkurnaloba, Control – sakontrolo jgufi.
da
klinikuri kvlevebi paralelur jgufebSi
am modelis ilustracia:
skriningi _ CarTva _mosamzadebeli periodi _ sawyisi
mdgomareoba _ randomizacia _
mkurnaloba a _ gamosavali a
mkurnaloba b _ gamosavali b
sadac a, b – sxvadasxva mkurnalobaa an s/s doza an placebo.
klinikuri kvlevebi paralelur jgufebSi
uaryofiTi mxare:
kvlevis es modeli ZviradRirebulia, xangrZlivi da saWiroebs
mravalricxovan dasakvirvebel jgufs (rodesac sakvlevi movlenis
ganviTaTrebis sixSire dabalia).
dadebiTi mxare:
_ metad obieqturia mkurnalobis efeqturobis gansazRvrisas da
zusti daskvnebis formulirebisas.
klinikur kvlevebs paralelur jgufebSi yvelaze
xSirad iyebeben kvlevebis Catarebis dros.
zogjer kvlevebis paralelur jgufebSi Catarebisas iyeneben an faqtorul an araerTgvarovan
modelebs.
faqtoruli modeli
faqtoruli modeli – es aris dizaini dafuZnebuli or an met
paralelur jgufze. mas iyeneben, rodesac Seiswavlian
sxvadasxva preperatebis kombinacias (an preparatis
sxvadasxva dozebs).
mas xSirad iyeneben kombinirebuli preparatebis
SefasebisaTvis.
uaryofiTi mxare: mravalricxovan sakvlev jgufs da Sedegad,
kvlevis Catarebisas danaxarjis gazrda.
faqtoruli modeli
mkurnaloba a
sakvlevi
pirebi
mkurnaloba b
mkurnaloba a+b
placebo
Sefaseba
araerTgvarovani modeli (“Terapiis Sewyveta”)
Withdrawal (Discontinuation) Design




kvlevis am modelis dros dasawyisSi yvela pacienti iRebs
eqsperimentuli mkurnalobas Semdeg ki, eqsperimentuli
mkurnalobis gasagrZeleblad xdeba Sesabamisi reaqciebis
mqone pacientebis randomizacia brma meTodis an
placebos gamoyenebiT.
araerTgvarovani modeli Cveulebriv gamoiyeneba
eqsperimentuli mkurnalobis efeqturobis Sesafaseblad
preparatis miRebis Sewyvetisa da recidivis an remisiis
registraciis gziT mkurnalobaze reaqciis gaCenisTanave..
kvlevis es dizaini gansakuTrebiT efeqturia im preparatebis
Sesafaseblad, romlebic Zneladgansakurnebeli daavadebebis
TerapiaSi gamoiyeneba. aseTi kvlevebis Catarebisas
pacientTa mxolod mcere procenti pasuxobs mkurnalobaze.
am dizains iyeneben, agreTve recidivebis Seswavlis drosac.
araerTgvarovani modeli
araerTgvarovani modelis sqema:
skriningi _ CarTva _ eqsperimentuli mkurnaloba _ reaqcia
mkurnalobaze _ mkurnalobaze mopasuxe pacientTa
randomizacia _ mkurnaloba.
uaryofiTi mxareebi:



mravalricxovani sakvlevi jgufi,
xangrZlivi kvleva,
eTikis sakiTxebi (SesaZlebelia saWiro gaxdes im preparatis
moxsna, romelic pacientis mdgomareobis gaunjobesebas
iwvevda).
klinikuri kvlevebi “jvaredin” modelSi


pacientebs randomizaciis gziT yofen jgufebad,
Semdeg maT utardebad erTnairi mkurnalobis
kursebi, magram sxvadasxva TanmimdevrobiT.
rogorc wesi, mkurnalobis kursebs Soris aris e.w.
“gamorecxvis” periodi, rom wina mkurnalobis
kursma zegavlena ar moaxdinos mis
Semdgomze.
kvlevis es dizaini ufro iafia, vinaidan sakvlev
pacientTa did jgufs ar saWiroebs.
klinikuri kvlevebi “jvaredin” modelSi
randomizacia
gamorecxvis
periodi t
Rx A
gamorecxvis
periodi
Rx A
monacemT
a analizi
sakvlevi
pirebi
Rx B
gamosavali
Rx B
gamosavali
klinikuri kvlevebi “jvaredin” modelSi
Двухпериодное клиническое испытание с перекрестным дизайном. *Population –populacia,
Assessment –gamokvleva, Eligible and willing subjects – Sesatyvisi da monawileobaze
Tanaxma pacientebi, Randomisation –randomizacia, Test –sacdeli mkurnaloba, Control
– sakontrolo jgufi.
klinikuri kvleva “jvaredin” modelSi
am modelis sqema:
skriningi _ mosamzadebeli periodi _
mdgomareobis kontroli _ randomizacia _
mkurnaloba a 1 jgufSi da mkurnaloba b 2
jgufSi _ gamorecxvis periodi _ mkurnaloba b
1 jgufSi da mkurnaloba a 2 jgufSi.
klinikuri fenotipis gansazRvra

CarTva/gamoricxvis kriteriumebi gansazRvraven sakvlev
klinikur fenotips.

CarTva/gamoricxvis kriteriumebi dakavSirebulia efeqturobisa
da usafrTxoebis sakiTxvebTan.
kvlevis sazRvrebi
gamosavlis zusti gansazRvra maRalxarisxiani
kvlevis Catarebis saSualebas iZleva.
xisti (mag., sikvdili) an rbili (mag., sicocxlis
xarisxi (QOL) - Sesabamisi kiTxvaris
gamoyenebiT miRebuli monacemebis
safuZvelze).
pirveladi (mag., arteriuli wneva
antihipertenziuli Terapiisas) an meoradi
(mag., insulti miokardiumis infarqtis dros).
ra ganapirobebs kvlevis warmatebiT Catarebas:





klinikuri problemis aqtualuroba.
klinikuri fenotipis swori gansazRvra.
ramdenad kargad asaxavs sakvlev
avadmyofTa jgufi mTeli populaciis Tvisebebs.
ramdenad Seesabameba kvlevis mizani
dizains.
adeqvaturi statistikuri analizis Catareba.
gmadlobT yuradRebisaTvis
Sample size
Размер выборки зависит от
• величины различия в частоте исходов между
группами (величина эффекта)
• альфа-ошибки (вывода об эффективности
лечения, которого на самом деле нет,0,05=1/20)
• бета-ошибки (0,20т.е.20%)
• природы данных
Таблица случайных чисел
Ряд
Колонка
12345
01
02
03
04
05
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09
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13
14
15
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17
66194 78240
00833 12111
47189 76396
46409 74626
.34450
36327 74185
12296 90822
72121 95268
92603 18813
38840 05959
85141 75047
30752 22986
99439 20389
39249 96777
04860 41613
17930 24649
79899 76801
67890
28926 43195
88000 86683
99951 72486
17469 22111
8ТО74
72135 77536
41623 60280
79152 41377
09091 90291
26903 33836
21155 59643
95260 82575
86692 93029
05173 33605
32918 42375
00794 31845
34061 49594
12345 67890
12345
67890
12345 67890
99547
24837
67299
61270
05755
62423
32483
87286
93723
33005
84825
62873
88925
96591
25684
75884
05275
28624
53758
99212
31074
68032
42187
90348
11881
68256
29481
10798
45515 70880
11274 64192
43782 84184
76175 42243
58432
3,4710
99103 25584
42772 10189
61816 72586
79607 51986
41081 51403
03718 58781
84295 48399
65452 20250
09398 52655
77580 67135
83808 56462
67953 22070
55624 90611
90599 78922
19985 68046
67083 49359
09325 09609
60561 79778
58555 88903
95426 42865
38012 31926
32119 34143
30634 73451
89047 68686
01843 33359
87772 98102
98917 58166
12108
52622
32991
15145
40282
73561
26309
44250
36876
50693
67389
63360
76873
68016
54305
30061
34900
14508
41230
16625 32511
68215 58036
03834 27618
09083 46772
49023 28701
09934 •37943
99610 90305
08151 93424
01223 67157
16562 32685
38172 62871
62295 66036
71685 36359
20063 50492
03656 53692
75231 59358
30397
15101
52728
6981
57846 61881
17436 01748
51417 52818
91536 42439
93391 89311
45869 47270
04117 13747
86189 14457
09778 49315
20528 58781
67143 69766
31442 39437
02656 09335
61344 28393
57085 11246
99430 86828
33706