• Aucun résultat trouvé

Development and clinical validation of a blood test based on 29-gene expression for early detection of colorectal cancer

N/A
N/A
Protected

Academic year: 2021

Partager "Development and clinical validation of a blood test based on 29-gene expression for early detection of colorectal cancer"

Copied!
31
0
0

Texte intégral

(1)

'HYHORSPHQWDQGFOLQLFDOYDOLGDWLRQRIDEORRGWHVWEDVHGRQJHQH H[SUHVVLRQIRUHDUO\GHWHFWLRQRIFRORUHFWDOFDQFHU



/DXUD &LDUORQL 6DKDU +RVVHLQLDQ 1DWVXNR ,PDL]XPL 6\OYDLQ 0RQQLHU%HQRLW &ULVWLQD1LFKLWD6HXQJ-DH0\XQJ-RR6XQJ.LP6L<RXQJ6RQJ7DH,O.LP

%RXGHZLMQYDQGHU:HJ5pP\0HLHU-DQ%RURYLFND&KULVWRSK%HJOLQJHU&pGULF

9DOOHW3KLOLSSH0DHUWHQ&XU]LR5HJJDQG*LDQ'RUWD 

1RYLJHQL[6$(SDOLQJHV6ZLW]HUODQG

'HSDUWPHQW RI *DVWURHQWHURORJ\ DQG +HSDWRORJ\ &HQWUH +RVSLWDOLHU 8QLYHUVLWDLUH

9DXGRLV/DXVDQQH6ZLW]HUODQG

$VDQ0HGLFDO&HQWUH'HSDUWPHQWRI*DVWURHQWHURORJ\8QLYHUVLW\RI8OVDQ&ROOHJH

RI0HGLFLQH6HRXO6RXWK.RUHD

'HSDUWPHQW RI ,QWHUQDO 0HGLFLQH 6HRXO 1DWLRQDO 8QLYHUVLW\ &ROOHJH RI 0HGLFLQH

6HRXO6RXWK.RUHD

6HYHUDQFH+RVSLWDO'LYLVLRQRI*DVWURHQWHURORJ\'HSDUWPHQWRI,QWHUQDO0HGLFLQH

<RQVHL8QLYHUVLW\&ROOHJHRI0HGLFLQH6HRXO6RXWK.RUHD

6SLWDO7KXQ*DVWURHQWHURORJ\7KXQ6ZLW]HUODQG

.DQWRQVVSLWDO /LHVWDO *DVWURHQWHURORJ\ +HSDWRORJ\ DQG 1XWULWLRQ 'HSDUWPHQW

8QLYHUVLW\+RVSLWDO/LHVWDO6ZLW]HUODQG

.DQWRQVVSLWDO 6W*DOOHQ 'HSDUWPHQW RI *DVWURHQWHURORJ\ DQG +HSDWRORJ\

6W*DOOHQ6ZLW]HUODQG

8QLYHUVLWlWVVSLWDO%DVHO'HSDUWPHQWRI%LRPHGLFLQH%DVHO6ZLW]HUODQG (QVHPEOH+RVSLWDOLHUGHOD&{WH6XUJHU\6HUYLFHV0RUJHV6ZLW]HUODQG &OLQLTXH&HFLO*DVWURHQWHURORJ\/DXVDQQH6ZLW]HUODQG

http://doc.rero.ch

Published in "Clinical Cancer Research doi:

10.1158/1078-0432.CCR-15-2057, 2016"

which should be cited to refer to this work.

(2)

'HSDUWPHQW RI 0HGLFLQH )DFXOW\ RI 6FLHQFH 8QLYHUVLW\ RI )ULERXUJ )ULERXUJ 6ZLW]HUODQG /&6+DQG1,FRQWULEXWHGHTXDOO\WRWKLVZRUN  5XQQLQJWLWOH%ORRGWHVWIRUFRORUHFWDOFDQFHUGHWHFWLRQ 

.H\ZRUGV &RORUHFWDO FDQFHU VFUHHQLQJ EORRG WHVW JHQH VLJQDWXUH WXPRU ELRPDUNHUV



)LQDQFLDOVXSSRUW7KLVZRUNZDVVXSSRUWHGE\1RYLJHQL[6$DQG'LDJQRSOH[6$ 

&RUUHVSRQGLQJ $XWKRUV 3URI &XU]LR 5HJJ 'HSDUWPHQW RI 0HGLFLQH )DFXOW\ RI 6FLHQFH 8QLYHUVLW\ RI )ULERXUJ  5XH $OEHUW *RFNHO &+ )ULERXUJ 6ZLW]HUODQG (PDLO FXU]LRUXHJJ#XQLIUFK; 3URI *LDQ 'RUWD 'HSDUWPHQW RI *DVWURHQWHURORJ\DQG+HSDWRORJ\&HQWUH+RVSLWDOLHU8QLYHUVLWDLUH9DXGRLV5XHGX %XJQRQ&+/DXVDQQH6ZLW]HUODQG(PDLOJLDQGRUWD#FKXYFK



'LVFORVXUH RI 3RWHQWLDO &RQIOLFWV RI ,QWHUHVW /& 6+ 60% DQG &5 DUH FRIRXQGHUV HPSOR\HHV DQG RZQ VWRFNV RI 1RYLJHQL[ 6$ *' LV DQ DGYLVRU WR 1RYLJHQL[ 6$ ZLWK QR ILQDQFLDO LQWHUHVW LQ WKH FRPSDQ\ 1, ZDV DQ HPSOR\HH RI 1RYLJHQL[ 6$ &5 /& DQG 60% DUH FRLQYHQWRUV RI WKH SDWHQW ³Biomarker combinations for detection of colorectal cancer” 180%(5 86 5HPDLQLQJ DXWKRUVGHFODUHQRFRQIOLFWRILQWHUHVW



:RUGFRXQW0DLQWH[W ZLWKRXWWDEOHDQGILJXUHOHJHQGVDQGUHIHUHQFHV  7RWDO1XPEHURI7DEOHDQG)LJXUH

(3)

$%675$&7

3XUSRVH $ EORRG WHVW IRU HDUO\ GHWHFWLRQ RI FRORUHFWDO FDQFHU &5&  LV D YDOXDEOH WRRO IRU WHVWLQJ DV\PSWRPDWLF LQGLYLGXDOV DQG UHGXFLQJ &5&UHODWHG PRUWDOLW\ 7KH REMHFWLYH RI WKLV VWXG\ ZDV WR GHYHORS DQG YDOLGDWH D QRYHO EORRG WHVW DEOH WR GLIIHUHQWLDWHSDWLHQWVZLWK&5&DQGDGHQRPDWRXVSRO\SV $3 IURPLQGLYLGXDOVZLWKD QHJDWLYHFRORQRVFRS\

([SHULPHQWDO 'HVLJQ $ FDVHFRQWURO PXOWLFHQWHU FOLQLFDO VWXG\ ZDV GHVLJQHG WR FROOHFW EORRG VDPSOHV IURP SDWLHQWV UHIHUUHG IRU FRORQRVFRS\ RU VXUJHU\ 3UHGLFWLYH DOJRULWKPV ZHUH GHYHORSHG RQ  FRQWUROV  ODUJH $3 /$3  •FP  &5& DQG LQGHSHQGHQWO\YDOLGDWHGRQFRQWUROV/$3&5& 6WDJHV,,, DVZHOODV RQFDVHVLQFOXGLQJRWKHUFRORUHFWDOILQGLQJVDQGGLVHDVHVRWKHUWKDQ&5&7KH WHVW LV EDVHG RQ D JHQH SDQHO H[SUHVVHG LQ SHULSKHUDO EORRG PRQRQXFOHDU FHOOV DORQHRULQFRPELQDWLRQZLWKHVWDEOLVKHGSODVPDWXPRUPDUNHUV

5HVXOWV7KHJHQHDOJRULWKPGHWHFWHG&5&DQG/$3ZLWKDVHQVLWLYLW\RI DQGUHVSHFWLYHO\ZLWKVSHFLILFLW\&RPELQDWLRQZLWKWKHSURWHLQWXPRU PDUNHUV &($ DQG &<)5$ UHVXOWHG LQ D VSHFLILFLW\ LQFUHDVH   ZLWK D VHQVLWLYLW\IRU&5&DQG/$3GHWHFWLRQRIDQGUHVSHFWLYHO\

&RQFOXVLRQV:HUHSRUWWKHYDOLGDWLRQRIDQRYHOEORRGWHVW&ROR[ŠIRUWKHGHWHFWLRQ RI&5&DQG/$3EDVHGRQDJHQHSDQHODQGWKH&($DQG&<)5$SODVPD ELRPDUNHUV 7KH SHUIRUPDQFH DQG FRQYHQLHQFH RI WKLV URXWLQH EORRG WHVW SURYLGHV SK\VLFLDQVDXVHIXOWRROWRWHVWDYHUDJHULVNLQGLYLGXDOVXQZLOOLQJWRXQGHUJRXSIURQW FRORQRVFRS\



(4)

75$16/$7,21$/5(/(9$1&(

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¶VSHUIRUPDQFHLVFRQVLVWHQWZLWKLWVXVHDVD&5&GHWHFWLRQWRROIRUDYHUDJH ULVN LQGLYLGXDOV UHOXFWDQW WR XQGHUJR XSIURQW FRORQRVFRS\ 7KLV VWXG\ LV EHLQJ IROORZHGE\DSURVSHFWLYHVWXG\WRPRQLWRUDQGIXUWKHUHYDOXDWHSHUIRUPDQFHRIWKH WHVW LQ GDLO\ FOLQLFDO SUDFWLFH )LQDOO\ WKLV WHVW PLJKW EHFRPH D XVHIXO RSWLRQ WR LQFUHDVHFRPSOLDQFHRIDYHUDJHULVNLQGLYLGXDOVWR&5&VFUHHQLQJ





(5)

,1752'8&7,21

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

(6)

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

7KH REMHFWLYH RI WKH SUHVHQW VWXG\ ZDV WR XVH WKLV JHQH SDQHO WR GHYHORS DQG YDOLGDWH D EORRG WHVW WKDW GLVFULPLQDWHV SDWLHQWV ZLWK &5& DQG $3 IURP LQGLYLGXDOV ZLWKRXW OHVLRQV 7KH FOLQLFDO VHQVLWLYLW\ DQG VSHFLILFLW\ RI WKH WHVW ZHUH YDOLGDWHG LQ D PXOWLFHQWHU FDVHFRQWURO VWXG\ )LQDOO\ ZH LQYHVWLJDWHG ZKHWKHU FRPELQLQJWKHQHZO\GHYHORSHGJHQHWHVWZLWKSURWHLQWXPRUPDUNHUVDOUHDG\LQ URXWLQHFOLQLFDOXVHIRUFDQFHUPDQDJHPHQWZRXOGEHQHILWWKHWHVW¶VDFFXUDF\

(7)

0(7+2'6 6WXG\GHVLJQ

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



6WXG\SRSXODWLRQ

7KHVWXG\UHFUXLWHGVXEMHFWVROGHUWKDQ\HDUVZKRZHUHUHIHUUHGE\JHQHUDO SUDFWLWLRQHUV IRU WKH JUHDW PDMRULW\ a  IRU D GLDJQRVWLF FRORQRVFRS\ DQG IRU D PLQRULW\ a  IRU D VFUHHQLQJ FRORQRVFRS\ 0RVW RI WKH &5& FDVHV   ZHUH UHFUXLWHGDPRQJVXEMHFWVZKRZHUHVFKHGXOHGIRUVXUJHU\

6XEMHFWVZLWKDSHUVRQDOKLVWRU\RISRO\SV&5&RWKHUW\SHVRIFDQFHURUZLWK IDPLO\KLVWRU\LQGLFDWLQJKLJKULVNIRU&5& •ILUVWGHJUHHUHODWLYHVZLWK&5&RU• ZLWK &5& DW WKH DJH  \HDUV IDPLOLDO SRO\SRVLV RU /\QFK V\QGURPH  ZHUH QRW HOLJLEOHIRUWKHVWXG\

 )ROORZLQJGLDJQRVLVWKHHQUROOHGSDUWLFLSDQWVZHUHUHWURVSHFWLYHO\DOORFDWHGWR FOLQLFDOO\ SUHGHILQHG JURXSV DV VXPPDUL]HG LQ )LJ  0DLQ VWXG\ JURXSV LQFOXGHG FRQWUROVODUJH$3 /$3 DQG&5&6XEMHFWVLQWKHFRQWUROJURXSZHUHFOHDUIURPDQ\ FRORUHFWDOOHVLRQVLQFOXGLQJK\SHUSODVWLFSRO\SVDQGVPDOODGHQRPDWRXVSRO\SV7KH /$3JURXSLQFOXGHGSDWLHQWVZLWKDWOHDVWRQHDGHQRPD•FPDQGQR&5&OHVLRQ

(8)

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³QRQ SHUSURWRFRO´ DQG LQWHQGHG WR EH DQDO\]HGVHSDUDWHO\WRWHVWWKHDOJRULWKPUHVSRQVHRQDODUJHUVSHFWUXPRIPHGLFDO FRQGLWLRQVDQGFRPRUELGLWLHV



&OLQLFDOSURFHGXUHV

$ FRORQRVFRS\ ZDV SHUIRUPHG IRU DOO VWXG\ SDWLHQWV H[FHSW IRU WKRVH ZLWK PDOLJQDQFLHV RWKHU WKDQ &5& GXH WR HWKLFDO UHDVRQV &RORQRVFRS\ WR WKH FHFXP

(9)

ZDVUHTXLUHGLQDOOFDVHVH[FHSWIRU&5&SDWLHQWVZLWKDVWHQRVLVFDXVHGE\DWXPRU PDVV 5HVHFWHG /$3 RU &5& WLVVXH ZHUH VHQW WR D FHQWUDO SDWKRORJ\ ERDUG FRPSRVHGRIWKUHHLQGHSHQGHQWSDWKRORJLVWVEOLQGHGWRDOOVXEMHFWLQIRUPDWLRQJURXS DOORFDWLRQ DQG DVVHVVPHQWV PDGH E\ RWKHU SDWKRORJLVWV 6XSSOHPHQWDU\ 0DWHULDOV DQG0HWKRGV 

)RU HDFK SDUWLFLSDQW  PO RI SHULSKHUDO EORRG ZDV FROOHFWHG LQWR  [  PO 9DFXWDLQHUŠ &37Œ WXEHV %HFWRQ 'LFNLQVRQ )UDQNOLQ /DNHV 1-  EHIRUH RU LPPHGLDWHO\ DIWHU FRORQRVFRS\ 0RVW RI WKH VDPSOHV IURP VXEMHFWV GLDJQRVHG ZLWK &5& UHTXLULQJ D VXUJHU\ ZHUH FROOHFWHG XS WR  ZHHNV DIWHU FRORQRVFRS\ ,Q DOO FDVHV EORRG ZDV FROOHFWHG SULRU WR SRO\S UHVHFWLRQ DQG SULRU WR DQ\ PHDVXUHV LQ SUHSDUDWLRQIRUVXUJHU\RUDQ\FDQFHUVSHFLILFWUHDWPHQW



/DERUDWRU\SURFHGXUHV

6DPSOHSUHSDUDWLRQDQGDQDO\VLVZHUHSHUIRUPHGLQDEOLQGHGPDQQHUE\ODERUDWRU\ SHUVRQQHO 3%0& VHSDUDWLRQ ZDV SHUIRUPHG ORFDOO\ ZLWKLQ  KRXUV DFFRUGLQJ WR 9DFXWDLQHUŠ &37Œ WXEH PDQXIDFWXUHU¶V LQVWUXFWLRQV 3%0& SHOOHWV ZHUH UHVXVSHQGHG DQG VWRUHG DW ƒ& 3ODVPD IURP HDFK VDPSOH ZDV FROOHFWHG DQG VWRUHGDWƒ&

$XWRPDWHG SXULILFDWLRQ RI WRWDO 51$ IURP 3%0& SHOOHWV ZDV SHUIRUPHG DW D FHQWUDO ODERUDWRU\ 51$ LQWHJULW\ ZDV DQDO\]HG DQG RQ DYHUDJH 51$ VDPSOHV VKRZHGD51$LQWHJULW\QXPEHU 5,1 RI“51$VDPSOHVZLWK5,1ZHUH FRQVLGHUHGRISRRUTXDOLW\DQGGLVFDUGHG51$VDPSOHVZHUHDOLTXRWHGDQGVWRUHGDW ƒ&

)RUHDFKVDPSOHQJRIWRWDO51$ZDVUHYHUVHWUDQVFULEHGLQWRF'1$XVLQJ WKH 6XSHU6FULSWŠ 9,/2 F'1$ 6\QWKHVLV .LW DFFRUGLQJ WR WKH PDQXIDFWXUHU¶V LQVWUXFWLRQV 5HDOWLPH 3&5 DQDO\VLV ZDV SHUIRUPHG RQ WKH /LJKWF\FOHU 

(10)

LQVWUXPHQWV XVLQJD JHQHSDQHO SUHYLRXVO\ UHSRUWHG   %ULHIO\ 3&5 UHDFWLRQV ZHUH FDUULHG RXW RQ D ZHOO SODWH SUHORDGHG ZLWK 5HDO7LPH UHDG\ &XVWRP 57 T3&5 DVVD\V XVLQJ5HDO7LPH5HDG\Œ'1$ 3UREHV 0DVWHU 0L[ *HQHH[SUHVVLRQ YDOXHV &S  ZHUH QRUPDOL]HG E\ WKH ǻ&7 PHWKRG XVLQJ WKH PHDQ RI WKH WKUHH KRXVHNHHSLQJJHQHV53/31$&$DQG737

3ODVPD FRQFHQWUDWLRQ RI &($ &<)5$ &$ DQG &$ WXPRU ELRPDUNHUVZHUHPHDVXUHGIRUHDFKSDWLHQWRQWKH$UFKLWHFWLPPXQRDVVD\DQDO\]HU SODWIRUPDFFRUGLQJWRWKHPDQXIDFWXUHU¶VLQVWUXFWLRQV

'HWDLOV RQ WKH HTXLSPHQW XVHG GXULQJ WKH ODERUDWRU\ SURFHGXUHV DQG UHODWLYH PDQXIDFWXUHUVFDQEHIRXQGLQ6XSSOHPHQWDU\0DWHULDOVDQG0HWKRGV



6WDWLVWLFDOGHVLJQDQGPRGHOLQJ

7KH VWXG\ DLPHG DW HQUROOLQJ  SDUWLFLSDQWV LQ RUGHU WR KDYH  HYDOXDEOH VXEMHFWV¶ VDPSOHV 2I WKRVH  ZHUH H[SHFWHG WR EH HTXDOO\ GLVWULEXWHG EHWZHHQ WKH  PDLQ VWXG\ JURXSV FRQWURO /$3 DQG &5&  IRU WKH GHYHORSPHQW DQG FOLQLFDO YDOLGDWLRQ RI WKH WHVW 7KH UHPDLQLQJ VXEMHFWV SUHVHQWLQJ ZLWK RWKHU SUHGHILQHG GLVHDVHVZHUHDOORFDWHGWRVHFRQGDU\JURXSVIRUWHVWLQJWKHDOJRULWKPVSHFLILFLW\,Q RUGHUWRUHDFKDVLJQLILFDQFHOHYHOĮ DQGDSRZHUȕ WKHVWXG\UHTXLUHG DW OHDVW  FRQWUROV  &5& DQG  /$3 2XW RI WKRVH  FRQWUROV  &5& DQG  /$3 KDG WR EH FROOHFWHG DW WKH 6ZLVV VLWHV 6DPSOHV IURP WKH WKUHH PDLQ JURXSVZHUHVWUDWLILHGE\JHQGHUDJHVLWH&5&VWDJHDQG/$3VL]HDQGUDQGRPO\ GLVWULEXWHGLQWRWUDLQLQJYDOLGDWLRQDQG7HVW6HWLQWKHSURSRUWLRQRIDQG  UHVSHFWLYHO\ )LJ   7UDLQLQJ DQG YDOLGDWLRQ VHWV ZHUH XVHG LQ WKH GLVFRYHU\ SKDVHWRGHILQHWKHSUHGLFWLYHDOJRULWKPVLQFOXGLQJVDPSOHVSUHYLRXVO\XVHGIRU WKHLGHQWLILFDWLRQRIWKHJHQHSDQHO  ,QWKHWHVWLQJSKDVHWKHDOJRULWKPVZHUH YDOLGDWHGRQ7HVW6HW7HVW6HWFROOHFWHGLQWKHH[WHQVLRQVWXG\DQG7HVW6HW

(11)

ZKLFK LQFOXGHG ³QRQ SHUSURWRFRO´ FRQWURO /$3 DQG &5& VXEMHFWV 6DPSOHV IURP VXEMHFWVZLWKRWKHUFRORUHFWDOOHVLRQVRUGLVHDVHVZHUHXVHGWRWHVWWKHSRVLWLYHUDWH RIWKHSUHGLFWLYHDOJRULWKPV

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Š

6SHFLILFLW\ ZDV HVWLPDWHG DV íSRVLWLYLW\ DPRQJ VXEMHFWV EHORQJLQJ WR WKH FRQWUROJURXS)RUWHVWFKDUDFWHULVWLFVFRQILGHQFHLQWHUYDOVZHUHFRPSXWHGZLWK WKHXVHRIDQH[DFWELQRPLDOWHVW

7KH5VWDWLVWLFVHQYLURQPHQWZDVXVHGIRUDOOVWDWLVWLFDODQDO\VHV

(12)

5(68/76 

6WXG\SRSXODWLRQ

2XW RI  HQUROOHG VXEMHFWV  ZHUH FRQVLGHUHG IXOO\ HYDOXDEOH   2I WKRVH  ZHUH UHFUXLWHG LQ 6ZLW]HUODQG DQG  LQ 6RXWK .RUHD 7KLV UHSRUW IRFXVHVRQWKH6ZLVVGDWDVHWRQO\.RUHDQGDWDZLOOEHSUHVHQWHGVHSDUDWHO\

,Q WKH 6ZLVV FROOHFWLYH WKH SHUSURWRFRO SRSXODWLRQ ZDV FRQVWLWXWHG RI  SDUWLFLSDQWV )LJ   LQFOXGLQJ  FRQWURO VXEMHFWV  /$3 DQG  &5& SDWLHQWV IURPVWDJHV,WR,9DVZHOODVVXEMHFWVGLDJQRVHGZLWKRWKHUW\SHVRIFRORUHFWDO OHVLRQV HJVPDOODGHQRPDVK\SHUSODVWLFSRO\SV VROLGFDQFHUVRURWKHUGLVHDVHV VXFK DV LQIODPPDWRU\ ERZHO GLVHDVHV RU GLYHUWLFXOLWLV IRU WHVWLQJ WKH DOJRULWKP VSHFLILFLW\ ,Q DGGLWLRQ  FDVHV FODVVLILHG DV ³QRQ SHUSURWRFRO´ ZHUH HQUROOHG IRU WHVWLQJ WKH DOJRULWKP EHKDYLRU RQ D ODUJHU VSHFWUXP RI PHGLFDO FRQGLWLRQV DQG FR PRUELGLWLHV'HPRJUDSKLFDQGFOLQLFDOFKDUDFWHULVWLFVRIWKHVXEMHFWVDUHUHSRUWHGLQ 7DEOH6XEMHFWVLQWKHFRQWURO/$3DQG&5&JURXSVKDGDPHDQDJHRI DQG  UHVSHFWLYHO\ 7KH FRQWURO JURXS HQUROOHG  ZRPHQ DQG  PHQ ZKHUHDVWKH/$3DQG&5&JURXSHQUROOHGDQGRIPHQUHVSHFWLYHO\



JHQHH[SUHVVLRQDQDO\VLV

$OO EORRG VDPSOHV ZHUH SURILOHG ZLWK D JHQH SDQHO 6XSSOHPHQWDU\ 7DEOH 6  SUHYLRXVO\UHSRUWHGDQGGLVFRYHUHGWKURXJKDFRPELQHGXQLYDULDWHDQGPXOWLYDULDWH DSSURDFK  1RGLIIHUHQFHVLQQRUPDOL]HGJHQHH[SUHVVLRQZHUHREVHUYHGDFURVV FROOHFWLQJ FHQWHUV GDWD QRW VKRZQ  RU DFURVV GLIIHUHQW DJH FDWHJRULHV ZLWKLQ WKH FRQWURORUWKH/$3JURXS 6XSSOHPHQWDU\7DEOH6 $IHZJHQHVZHUHIRXQGWREH GLIIHUHQWLDOO\ H[SUHVVHG EHWZHHQ LQGLYLGXDOV RI GLIIHUHQW DJH FODVVHV LQ WKH &5& JURXSDVZHOODVEHWZHHQPHQDQGZRPHQZLWKLQDOOJURXSV7KHVHGLIIHUHQFHVLQ

(13)

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

7KH0*0&DOJRULWKPZDVDOVRWHVWHGRQVXEMHFWVZLWKRWKHUGLVHDVHV 7DEOH DQG 6XSSOHPHQWDU\ 7DEOH 6  1RQJDVWURLQWHVWLQDO *,  LQIODPPDWRU\ DQG YLUDO GLVHDVHV VKRZHG D ORZ UDWH RI SRVLWLYLW\ FRPSDUDEOH WR WKH FRQWUROV ZKHUHDV ,%' DQGRWKHU*,GLVHDVHVKDGDKLJKHUSRVLWLYLW\UDWH7KHRWKHUFDQFHUVVKRZHGDYHU\ KHWHURJHQHRXVEHKDYLRUUDQJLQJIURPDSRVLWLYHUDWHRIIRUSDQFUHDWLFFDQFHU WRIRURWKHU*,FDQFHUV

(14)

7KH DOJRULWKP ZDV IXUWKHU WHVWHG RQ WKH 7HVW 6HW  DQG WKH UHVXOWV DUH SUHVHQWHG LQ 6XSSOHPHQWDU\ 7DEOH 6 7KH\ FRQILUPHG WKH ILQGLQJV RI WKH SHU SURWRFRO DQDO\VHV :KHQ WKHVH VDPSOHV ZHUH DGGHG WR WKH SHUSURWRFRO VDPSOHV 0*0& VHQVLWLYLW\ IRU /$3 DQG &5& ZDV  DQG  UHVSHFWLYHO\ ZLWK D VSHFLILFLW\RI 7DEOH 



&RPELQDWLRQRIWKH0*0&DOJRULWKPZLWKSURWHLQWXPRUPDUNHUV

$PRQJ WKH  WXPRU PDUNHUV DQDO\]HG &($ DQG &<)5$ VKRZHG WKH PRVW VLJQLILFDQWSYDOXHV OHVVWKDQ IRUGLVFULPLQDWLRQEHWZHHQWKH&5&DQGFRQWURO JURXSV DQG WKH KLJKHVW DUHD XQGHU WKH FXUYH $8&  IRU &5& DQG FRQWURO FODVVLILFDWLRQ GDWDQRWVKRZQ ,QWKHWUDLQLQJVHWWKHVHWXPRUPDUNHUVGLVSOD\HGD VSHFLILFLW\ RI  DQG  DQG VHQVLWLYLW\ IRU &5& GHWHFWLRQ RI  DQG  UHVSHFWLYHO\ 7KHVH UHVXOWV ZHUH FRQILUPHG LQ WKH YDOLGDWLRQ VHW ZLWK D VSHFLILFLW\ RI  DQG  DQG VHQVLWLYLW\ IRU &5& RI  DQG  UHVSHFWLYHO\&($DQG&<)5$VHQVLWLYLW\ZDVGLUHFWO\FRUUHODWHGWR&5&VWDJH GDWDQRWVKRZQ 

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

(15)

VOLJKWO\ KLJKHU GHWHFWLRQ UDWH ZDV REVHUYHG LQ WKH FDVHV FROOHFWHG EHIRUH VXUJHU\ YV +RZHYHUWKLVGLIIHUHQFHZDVQRWVWDWLVWLFDOO\VLJQLILFDQW S! 

'XHWRWKHREVHUYHGGLIIHUHQFHVLQDJHDQGVH[GLVWULEXWLRQEHWZHHQWKHFRQWURO DQG WKH &5& JURXS DQG GLIIHUHQFHV LQ WKH H[SUHVVLRQ OHYHOV RI VRPH LQGLYLGXDO ELRPDUNHUV VWDWLVWLFDO WHVWLQJ ZDV FDUULHG RXW WR HYDOXDWH D SRVVLEOH FRQIRXQGLQJ HIIHFW RI DJH RU VH[ RQ &5& GLVFULPLQDWLRQE\ WKH DOJRULWKP EDVHGRQ WKH JHQH SDQHO1RQHRIWKHFRQVLGHUHGIDFWRUVVKRZHGDQDVVRFLDWLRQZLWKWKHWHVWUHVXOW S YDOXH!  6XSSOHPHQWDU\ 7DEOH 6  0RUHRYHU DJH DQG VH[ ZHUH WHVWHG DV FRYDULDWHV LQ PXOWLYDULDWH ORJLVWLF UHJUHVVLRQ DQDO\VLV 1RQH RI WKHVH WZR YDULDEOHV SOD\HGDVWDWLVWLFDOO\VLJQLILFDQWUROHLQGLIIHUHQWLDWLQJWKHFRQWUROIURP&5&JURXS

 

',6&866,21

(DUO\ GHWHFWLRQ RI &5& GUDPDWLFDOO\ LPSURYHV WKH FOLQLFDO RXWFRPH RI WKH GLVHDVH DQGUHJXODUVFUHHQLQJKDVSURYHQWRUHGXFHPRUWDOLW\  7KH³JROGVWDQGDUG´IRU$3 DQG &5& GHWHFWLRQ LV FRORQRVFRS\ ,W KDV WKH KLJKHVW VHQVLWLYLW\ IRU $3 RU &5& DPRQJDOOVFUHHQLQJWHVWVDQGKDVWKHDGYDQWDJHWRDOORZGLUHFWYLVXDOL]DWLRQRIWKH HQWLUH FRORQDQG UHPRYDORI SUHFDQFHURXVOHVLRQV +RZHYHUGXHWR WKH XQSOHDVDQW ERZHOSUHSDUDWLRQUHTXLUHGE\WKHPHWKRGDVZHOODVLWVLQYDVLYHQDWXUHFRPSOLDQFH WRVFUHHQLQJFRORQRVFRS\UHPDLQVXQVDWLVIDFWRULO\ORZ2WKHUUHFRPPHQGHGRSWLRQV DUHVWRROEDVHGWHVWVVXFKDVWKHJXDLDFRULPPXQRFKHPLFDO)2%7VRUWKHUHFHQWO\ )'$DSSURYHG VWRRO '1$ WHVW &RORJXDUGŠ    6WRRO WHVWV UHTXLUH VWRRO PDQLSXODWLRQ DW KRPH ZKLFK LV XQDSSHDOLQJ DQG LQFRQYHQLHQW WR VRPH WKXV FRQWULEXWLQJWRWKHORZVFUHHQLQJFRPSOLDQFHGHVSLWHWKHLUSURPLVLQJSHUIRUPDQFHV

$Q DFFXUDWH EORRG WHVW ZRXOG EH DQ DWWUDFWLYH DOWHUQDWLYH IRU DV\PSWRPDWLF DYHUDJH ULVN LQGLYLGXDOV UHOXFWDQW WR XQGHUJR VFUHHQLQJ E\ D VWRRO WHVW RU

(16)

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

$EORRGWHVWEDVHGRQGHWHFWLQJDEHUUDQWO\PHWK\ODWHG'1$LQWKH6HSWLQJHQH (SL SUR&RORQŠ  KDV UHFHQWO\ EHHQ DSSURYHG E\ WKH )'$ ,Q D ODUJH SURVSHFWLYH VFUHHQLQJVWXG\WKHWHVWVKRZHGVHQVLWLYLW\IRU&5&RIDWVSHFLILFLW\RI7KH WHVW ZDV QRW DEOH WR GHWHFW DGYDQFHG DGHQRPDV VKRZLQJ VHQVLWLYLW\ HTXLYDOHQW WR WKHIDOVHSRVLWLYHGHWHFWLRQUDWHLQWKHFRQWUROJURXS YV   

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

7KHWHVWZDVDOVRHYDOXDWHGLQSDWLHQWVSUHVHQWLQJRWKHUFRORUHFWDOOHVLRQVDQG D YDULRXV VSHFWUXP RI GLIIHUHQW GLVHDVHV 7KH WHVW GHWHFWHG DURXQG  RI $3

(17)

VPDOOHU WKDQ  FP ,W ZRXOG EH RI LQWHUHVW WR HYDOXDWH KRZ WKLV GHWHFWLRQ UDWH FRUUHODWHV ZLWK WKH KLVWRORJ\ LH QRQDGYDQFHG YHUVXV DGYDQFHG $3 WKH ODWWHU UHSUHVHQWLQJDSSUR[LPDWHO\RIWKHVPDOO$3  

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

7KHSRVLWLYHUDWHRIWKHWHVWLQSDWLHQWVZLWK,%'DQGRWKHU*,EHQLJQGLVHDVHV ZDVFORVHWR6LQFHWKHVHSDWLHQWVDUHQRUPDOO\XQGHUFORVHVXUYHLOODQFHDQGRU DUH SUHVHQWLQJ V\PSWRPV WKH\ DUH FRQVLGHUHG LQHOLJLEOH IRU WHVWLQJ E\ WKLV NLQG RI WHVW

(18)

,Q FOLQLFDO SUDFWLFH WKLV WHVW ZLOO QRW EH DSSOLHG WR LQGLYLGXDOV GLDJQRVHG ZLWK RWKHU FDQFHUV :H QHYHUWKHOHVV HYDOXDWHG D OLPLWHG QXPEHU RI SDWLHQWV ZLWK PDOLJQDQFLHV RWKHU WKDQ &5& DQG IRXQG GLIIHUHQW GHJUHHV RI SRVLWLYLW\ 7KHVH H[SORUDWRU\REVHUYDWLRQVGLGQRW\LHOGUHOHYDQWFRQFOXVLRQVVLQFHWKHVWXG\ZDVQRW GHVLJQHGWRHYDOXDWHWKHWHVWIRUWKHHDUO\GHWHFWLRQRIFDQFHUVRWKHUWKDQ&5&DQG PRVWSDWLHQWVZHUHQRWLQYHVWLJDWHGE\FRORQRVFRS\

,Q VXPPDU\DQHZEORRGWHVWKDVEHHQGHYHORSHGDQGFOLQLFDOO\ YDOLGDWHG IRU GHWHFWLRQRI/$3DQG&5&EDVHGRQDJHQHH[SUHVVLRQSDQHODQGWKH&($DQG &<)5$SODVPDELRPDUNHUV7KHWHVW¶VSHUIRUPDQFHLVFRQVLVWHQWZLWKLWVXVHDV D &5& GHWHFWLRQ WRRO IRU DYHUDJH ULVN LQGLYLGXDOV UHOXFWDQW WR XQGHUJR XSIURQW FRORQRVFRS\7KLVFRQYHQLHQWDQGURXWLQHEORRGWHVWFDQKHOSLGHQWLI\LQGLYLGXDOVZKR ZLOOEHQHILWWKHPRVWIURPDFRORQRVFRS\$SURVSHFWLYHVWXG\LVFXUUHQWO\RQJRLQJWR PRQLWRUDQGIXUWKHUHYDOXDWHWKHSHUIRUPDQFHRIWKHWHVWLQGDLO\FOLQLFDOSUDFWLFH 

$&.12:/('*0(176

7KH DXWKRUV ZLVK WR WKDQN 6 7KHULDQRV IRU LQLWLDWLQJ DQG SURPRWLQJ WKH SURMHFW / :LHF]RUHFN IRU OHDGLQJ WKH FOLQLFDO VWXG\ 1 5RFKDW 0 &RUER] < 5LVVH - :\QHJHU DQG 1 /HYL IRU WKHLU WHFKQLFDO VXSSRUW LQ GDWD DFTXLVLWLRQ 9 /D )RQWDLQH IRU KHOSLQJ LQ UHFUXLWLQJ WKH SDWLHQWV / %DOGDVVLQ DQG 3 0RQQLHU%HQRLW IRU GDWD PDQDJHPHQW 'U 6 .KDOLO DQG 'U 1 9LHWWL9LROL IRU PHGLFDO GDWD UHYLHZ DQG & /HERXUJHRLV(0LOODQDQG%%+DVKHPLIRUFULWLFDOUHYLHZRIWKHPDQXVFULSW 

$XWKRU¶V&RQWULEXWLRQV6WXG\GHVLJQ6+1,*''HYHORSPHQWRIPHWKRGRORJ\ 6+ 60% /& &5 $FTXLVLWLRQ RI GDWD 1, 60% /& &1 <6 -6. 6-0 -% 50 %9': &% &9 30 'DWD DQDO\VLV DQG LQWHUSUHWDWLRQ 6+ /& 1, 60% &5 &1

(19)

*'0DQXVFULSWZULWLQJ/&6+1,&5&1*'6WXG\VXSHUYLVLRQ1,6+60% *'$OODXWKRUVDSSURYHGWKHILQDOGUDIWVXEPLWWHG



(20)

5()(5(1&(6

 )HUOD\ - 6RHUMRPDWDUDP , 'LNVKLW 5 (VHU 6 0DWKHUV & 5HEHOR 0 HW DO &DQFHU LQFLGHQFH DQG PRUWDOLW\ ZRUOGZLGH VRXUFHV PHWKRGV DQG PDMRU SDWWHUQVLQ*/2%2&$1,QW-&DQFHU(

 %UHQQHU+.ORRU03R[&3&RORUHFWDOFDQFHU/DQFHW  *DUERUJ.+ROPH2/REHUJ0.DODJHU0$GDPL+2%UHWWKDXHU0&XUUHQW

VWDWXVRIVFUHHQLQJIRUFRORUHFWDOFDQFHU$QQ2QFRO

 6KDXNDW $ 0RQJLQ 6- *HLVVHU 06 /HGHUOH )$ %RQG -+ 0DQGHO -6 HW DO /RQJWHUP PRUWDOLW\ DIWHU VFUHHQLQJ IRU FRORUHFWDO FDQFHU 1 (QJO - 0HG 

 $WNLQ:6(GZDUGV5.UDOM+DQV,:RROGUDJH.+DUW$51RUWKRYHU-0HWDO 2QFHRQO\IOH[LEOHVLJPRLGRVFRS\VFUHHQLQJLQSUHYHQWLRQRIFRORUHFWDOFDQFHU DPXOWLFHQWUHUDQGRPLVHGFRQWUROOHGWULDO/DQFHW

 &UX]DGR-6DQFKH]),$EHOODQ-03HUH]5LTXHOPH)&DUEDOOR)(FRQRPLF HYDOXDWLRQ RI FRORUHFWDO FDQFHU &5&  VFUHHQLQJ %HVW 3UDFW 5HV &OLQ *DVWURHQWHURO

 7LOVRQ/6KDUS/8VKHU&:DOVK&6:2&HLOOHDFKDLU$HWDO&RVWRIFDUH IRU FRORUHFWDO FDQFHULQ ,UHODQG D KHDOWK FDUHSD\HU SHUVSHFWLYH (XU - +HDOWK (FRQ

 /DQVGRUS9RJHODDU,.QXGVHQ$%%UHQQHU+&RVWHIIHFWLYHQHVVRIFRORUHFWDO FDQFHUVFUHHQLQJ(SLGHPLRO5HY

 *DQHSROD *$ 1L]LQ - 5XWOHGJH -5 &KDQJ '+ 8VH RI EORRGEDVHG ELRPDUNHUV IRU HDUO\ GLDJQRVLV DQG VXUYHLOODQFH RI FRORUHFWDO FDQFHU :RUOG - *DVWURLQWHVW2QFRO

 $GOHU $ *HLJHU 6 .HLO $ %LDV + 6FKDW] 3 GH9RV 7 HW DO ,PSURYLQJ FRPSOLDQFHWRFRORUHFWDOFDQFHUVFUHHQLQJXVLQJEORRGDQGVWRROEDVHGWHVWVLQ

(21)

SDWLHQWV UHIXVLQJ VFUHHQLQJ FRORQRVFRS\ LQ *HUPDQ\ %0& *DVWURHQWHURO 

 7DEHU -0 $VSLQZDOO /* +HLFKPDQ .$ .LQQH\ $< 3UHIHUHQFHV IRU EORRG EDVHG FRORQ FDQFHU VFUHHQLQJ GLIIHU E\ UDFHHWKQLFLW\ $P - +HDOWK %HKDY 

 /RUXVVR*5XHJJ&7KHWXPRUPLFURHQYLURQPHQWDQGLWVFRQWULEXWLRQWRWXPRU HYROXWLRQWRZDUGPHWDVWDVLV+LVWRFKHP&HOO%LRO

 3HGGDUHGGLJDUL 9* :DQJ ' 'XERLV 51 7KH WXPRU PLFURHQYLURQPHQW LQ FRORUHFWDOFDUFLQRJHQHVLV&DQFHU0LFURHQYLURQ

 0F$OOLVWHU 66 :HLQEHUJ 5$ 7KH WXPRXULQGXFHG V\VWHPLF HQYLURQPHQW DV D FULWLFDO UHJXODWRU RI FDQFHU SURJUHVVLRQ DQG PHWDVWDVLV 1DW &HOO %LRO 

 +DQDKDQ ' &RXVVHQV /0 $FFHVVRULHV WR WKH FULPH IXQFWLRQV RI FHOOV UHFUXLWHGWRWKHWXPRUPLFURHQYLURQPHQW&DQFHU&HOO

 /DXUHQW - +XOO () 7RXYUH\ & .XRQHQ ) /DQ 4 /RUXVVR * HW DO 3URDQJLRJHQLF IDFWRU 3O*) SURJUDPV &'E   P\HORPRQRF\WHV LQ EUHDVW FDQFHU GXULQJ GLIIHUHQWLDWLRQ RI WKHLU KHPDWRSRLHWLF SURJHQLWRUV &DQFHU 5HV 

 *XH[1&UHVSR,%URQ6,IWLFHQH7UHERX[$)DHVYDQ¶W+XOO(.KDURXEL6HW DO $QJLRJHQLF DFWLYLW\ RI EUHDVW FDQFHU SDWLHQWV¶ PRQRF\WHV UHYHUWHG E\ FRPELQHGXVHRIV\VWHPVPRGHOLQJDQGH[SHULPHQWDODSSURDFKHV3/26%LRO ,QSUHVV

 .XRQHQ ) /DXUHQW - 6HFRQGLQL & /RUXVVR * 6WHKOH -& 5DXVFK 7 HW DO ,QKLELWLRQ RI WKH .LW OLJDQGF.LW D[LV DWWHQXDWHV PHWDVWDVLV LQ D PRXVH PRGHO PLPLFNLQJ ORFDO EUHDVW FDQFHU UHODSVH DIWHU UDGLRWKHUDS\ &OLQ &DQFHU 5HV 

(22)

 1LFKLWD & &LDUORQL / 0RQQLHU%HQRLW 6 +RVVHLQLDQ 6 'RUWD * 5XHJJ & $ QRYHOJHQHH[SUHVVLRQVLJQDWXUHLQSHULSKHUDOEORRGPRQRQXFOHDUFHOOVIRUHDUO\ GHWHFWLRQRIFRORUHFWDOFDQFHU$OLPHQW3KDUPDFRO7KHU

 &LDUORQL / +RVVHLQLDQ 6 0RQQLHU%HQRLW 6 ,PDL]XPL 1 'RUWD * 5XHJJ & 'LVFRYHU\ RI D JHQH SDQHO LQ SHULSKHUDO EORRG PRQRQXFOHDU FHOOV IRU WKH GHWHFWLRQ RI FRORUHFWDO FDQFHU DQG DGHQRPDV XVLQJ KLJK WKURXJKSXW UHDOWLPH 3&53/R62QHH

 3DUN 0< +DVWLH 7 / UHJXODUL]DWLRQ SDWK DOJRULWKP IRU JHQHUDOL]HG OLQHDU PRGHOV-56WDW6RF%±

 )ULHGPDQ-+DVWLH77LEVKLUDQL55HJXODUL]DWLRQ3DWKVIRU*HQHUDOL]HG/LQHDU 0RGHOVYLD&RRUGLQDWH'HVFHQW-6WDW6RIWZ

 *RHPDQ -- / SHQDOL]HG HVWLPDWLRQ LQ WKH &R[ SURSRUWLRQDO KD]DUGV PRGHO %LRP-  9RVH0'6LPSOH*HQHWLF$OJRULWKP)RXQGDWLRQDQG7KHRU\0,73UHVV$QQ $UERU0,  3HQD5H\HV&$(YROXWLRQDU\IX]]\PRGHOLQJKXPDQGLDJQRVWLFGHFLVLRQV$QQ 1<$FDG6FL  'XDQ/ :X 5<H/ :DQJ+ <DQJ ;=KDQJ<HW DO 6$DQG 6$ DUH DVVRFLDWHG ZLWK FRORUHFWDO FDUFLQRPD SURJUHVVLRQ DQG FRQWULEXWH WR FRORUHFWDOFDUFLQRPDFHOOVXUYLYDODQGPLJUDWLRQYLD:QWEHWDFDWHQLQSDWKZD\ 3/R62QHH

 *XLWWHW / %RXYLHU 9 0DULRWWH 1 9DOOHH -3 $UVHQH ' %RXWUHX[ 6 HW DO &RPSDULVRQRIDJXDLDFEDVHGDQGDQLPPXQRFKHPLFDOIDHFDORFFXOWEORRGWHVW LQ VFUHHQLQJ IRU FRORUHFWDO FDQFHU LQ D JHQHUDO DYHUDJH ULVN SRSXODWLRQ *XW 

(23)

 ,PSHULDOH 7) 5DQVRKRII ') ,W]NRZLW] 6+ 0XOWLWDUJHW VWRRO '1$ WHVWLQJ IRU FRORUHFWDOFDQFHUVFUHHQLQJ1(QJO-0HG

 GH :LMNHUVORRWK 75 6WRRS (0 %RVVX\W 30 0HLMHU *$ YDQ %DOOHJRRLMHQ 0 YDQ 5RRQ $+ HW DO ,PPXQRFKHPLFDO IHFDO RFFXOW EORRG WHVWLQJ LV HTXDOO\ VHQVLWLYH IRU SUR[LPDO DQG GLVWDO DGYDQFHG QHRSODVLD $P - *DVWURHQWHURO 

 3DUN ', 5\X 6 .LP <+ /HH 6+ /HH &. (XQ &6 HW DO &RPSDULVRQ RI JXDLDFEDVHG DQG TXDQWLWDWLYH LPPXQRFKHPLFDO IHFDO RFFXOW EORRG WHVWLQJ LQ D SRSXODWLRQ DW DYHUDJH ULVN XQGHUJRLQJ FRORUHFWDO FDQFHU VFUHHQLQJ $P - *DVWURHQWHURO

 5R]HQ 3 /LSKVKLW] , %DUFKDQD 0 )ROORZXS RI SDWLHQWV XQGHUJRLQJ ERWK VHPLTXDQWLWDWHG LPPXQRFKHPLFDO IHFDO RFFXOW EORRG DQG FRORQRVFRS\ H[DPLQDWLRQV(XU-&DQFHU3UHY

 %HQQLQJ70'HOODHUW%*'LUNVHQ&'6HYHUHQV-/3UHIHUHQFHVIRUSRWHQWLDO LQQRYDWLRQV LQ QRQLQYDVLYH FRORUHFWDO FDQFHU VFUHHQLQJ $ ODEHOHG GLVFUHWH FKRLFHH[SHULPHQWIRUD'XWFKVFUHHQLQJFDPSDLJQ$FWD2QFRO 

 3RWWHU17+XUEDQ3:KLWH01:KLWORFN.'/RIWRQ'D\&(7HW]QHU5HWDO 9DOLGDWLRQ RI D UHDOWLPH 3&5EDVHG TXDOLWDWLYH DVVD\ IRU WKH GHWHFWLRQ RI PHWK\ODWHG6(37'1$LQKXPDQSODVPD&OLQ&KHP  7VDL)&6WUXP:%3UHYDOHQFHRIDGYDQFHGDGHQRPDVLQVPDOODQGGLPLQXWLYH FRORQSRO\SVXVLQJGLUHFWPHDVXUHPHQWRIVL]H'LJ'LV6FL  2UORZVND-+\SHUSODVWLFSRO\SRVLVV\QGURPHDQGWKHULVNRIFRORUHFWDOFDQFHU *XWDXWKRUUHSO\  +HLWPDQ6-5RQNVOH\3(+LOVGHQ5-0DQQV%-5RVWRP$+HPPHOJDUQ%5 3UHYDOHQFH RI DGHQRPDV DQG FRORUHFWDO FDQFHU LQ DYHUDJH ULVN LQGLYLGXDOV D

(24)

V\VWHPDWLFUHYLHZDQGPHWDDQDO\VLV&OLQ*DVWURHQWHURO+HSDWRO 

 +D]HZLQNHO<GH:LMNHUVORRWK756WRRS(0%RVVX\W30%LHUPDQQ.YDQGH 9LMYHU 0- HW DO 3UHYDOHQFH RI VHUUDWHG SRO\SV DQG DVVRFLDWLRQ ZLWK V\QFKURQRXV DGYDQFHG QHRSODVLD LQ VFUHHQLQJ FRORQRVFRS\ (QGRVFRS\ 

 0HODWR05L]]DUGL&1DUGRQ(6WDQWD*6FDUFHLQIRUPDWLRQDERXWWKHULVNRI FDQFHU LQ FRORUHFWDO K\SHUSODVWLF SROS\V DQG SRO\SRVLV $P - *DVWURHQWHURO 

 /DQJQHU & 6HUUDWHG DQG QRQVHUUDWHG SUHFXUVRU OHVLRQV RI FRORUHFWDO FDQFHU 'LJ'LV

 .LP.0/HH(-+D6.DQJ6<-DQJ.73DUN&.HWDO0ROHFXODUIHDWXUHV RI FRORUHFWDO K\SHUSODVWLF SRO\SV DQG VHVVLOH VHUUDWHG DGHQRPDSRO\SV IURP .RUHD$P-6XUJ3DWKRO

 2%ULHQ0-+\SHUSODVWLFDQGVHUUDWHGSRO\SVRIWKHFRORUHFWXP*DVWURHQWHURO &OLQ1RUWK$PYLLL

 -DQMXD +* +RJGDOO ( /LQQHPDQQ ' +\SHUSODVWLF SRO\SV RI WKH FRORQ DQG UHFWXP  UHFODVVLILFDWLRQ %5$) DQG .5$6 VWDWXV LQ LQGH[ SRO\SV DQG VXEVHTXHQWFRORUHFWDOFDUFLQRPD$30,6

 

(25)

),*85(/(*(1'6 

)LJXUH)ORZFKDUWVKRZLQJSDWLHQWGLVSRVLWLRQ 

)LJXUH  6WXG\ GHVLJQ GLDJUDP 7KH 7UDLQLQJ 9DOLGDWLRQ 7HVW 6HW  DQG  DQG SDUW RI VXEMHFWV ZLWK RWKHU ILQGLQJV DQG GLVHDVHV Q  FRQVWLWXWHG WKH SHUSURWRFRO FDVHV7HVW6HWDQGUHPDLQLQJSDWLHQWVZLWKRWKHUILQGLQJVDQGGLVHDVHV Q ZHUH HQUROOHGDVQRQSHUSURWRFROFDVHV   7DEOH/HJHQGV  7DEOH&OLQLFDODQGGHPRJUDSKLFFKDUDFWHULVWLFVRIWKHVWXG\SDUWLFLSDQWV 

7DEOH  6SHFLILFLW\ DQG VHQVLWLYLW\ RI WKH 0*0& DOJRULWKP IRU &5& DQG ODUJH $3GHWHFWLRQ



7DEOH  3RVLWLYH UDWH RI WKH 0*0& DQG 0*0&3 DOJRULWKPV IRU RWKHU FRORUHFWDOOHVLRQVDQGGLVHDVHV  7DEOH6SHFLILFLW\DQGVHQVLWLYLW\RIWKH0*0&3DOJRULWKPIRU&5&DQGODUJH $3GHWHFWLRQ    

http://doc.rero.ch

(26)
(27)
(28)

7DEOH&OLQLFDODQGGHPRJUDSKLFFKDUDFWHULVWLFVRIWKH VWXG\SDUWLFLSDQWV ĂƚĞŐŽƌLJ WĂƚŝĞŶƚ;ŶͿ ŐĞ;ŵĞĂŶц^Ϳ DĂůĞ;йͿ ŽŶƚƌŽů ϭϰϵ ϲϬ͘ϲцϳ͘ϴ ϰϲ >W ϭϬϯ ϲϳ͘ϯцϴ͘Ϯ ϲϰ͘ϭ ϭͲϮĐŵ ϱϳ ϲϳ͘ϱцϴ͘ϰ ϲϲ͘ϳ хϮĐŵ ϰϲ ϲϳ͘ϭцϴ͘ϭ ϲϬ͘ϵ ZĂ ϵϳ ϲϵ͘ϰцϵ͘ϳ ϲϭ͘ϵ ^ƚĂŐĞ/ ϮϮ ϳϭ͘Ϯцϵ͘Ϯ ϱϵ͘ϭ ^ƚĂŐĞ// ϮϮ ϲϵ͘ϴцϴ͘ϲ ϲϯ͘ϲ ^ƚĂŐĞ/// ϯϭ ϲϴ͘ϭцϭϮ͘ϯ ϱϰ͘ϴ ^ƚĂŐĞ/s ϮϮ ϲϵцϳ͘Ϭ ϳϮ͘ϳ KƚŚĞƌĐŽůŽƌĞĐƚĂůůĞƐŝŽŶƐĂŶĚ ĚŝƐĞĂƐĞƐ Ϯϰϱ Ͳ Ͳ WфϭĐŵ ϲϳ ϲϱ͘Ϯцϴ͘ϵ ϳϳ͘ϲ ,LJƉĞƌƉůĂƐƚŝĐƉŽůLJƉƐ ϲϭ ϲϬ͘ϰцϳ͘ϲ ϱϵ /ď ϭϰ ϱϴ͘ϳцϲ͘ϭ ϳϭ͘ϰ KƚŚĞƌ'/ĚŝƐĞĂƐĞƐĐ ϭϵ ϲϮ͘ϳцϭϬ͘ϯ ϰϮ͘ϭ /ŶĨůĂŵŵĂƚŽƌLJĚŝƐĞĂƐĞƐĚ ϭϭ ϲϱцϴ͘ϯ ϭϴ͘Ϯ ,ĞƉĂƚŝƚŝƐ͕,ĞƌƉĞƐ͕/^ ϭϬ ϲϭ͘ϴцϱ͘ϵ ϰϬ KƚŚĞƌĐĂŶĐĞƌƐ ϲϯ ϲϳ͘Ϯцϴ͘Ϭ ϳϭ͘ϰ EŽŶƉĞƌͲƉƌŽƚŽĐŽůĐĂƐĞƐ ϭϴϴ ϲϱ͘ϭцϭϬ͘Ϭ ϱϲ͘ϰ D

$OO &5& ZHUH DGHQRFDUFLQRPDV H[FHSW RQH VTXDPRXV FDUFLQRPD 7ZR ZHUH PXFLQXRV W\SH ď (LJKW&URKQ¶VGLVHDVHDQGXOFHUDWLYHFROLWLV Đ ,QFOXGLQJJDOOVWRQHVDQGGLYHUWLFXOLWLV Ě 7KUHHDXWRLPPXQHKHSDWLWLVSVRULDVLVDQGUKHXPDWRLGDUWKULWLV

http://doc.rero.ch

(29)

7DEOH6SHFLILFLW\DQGVHQVLWLYLW\RIWKH0*0&DOJRULWKPIRU&5&DQG ODUJH$3GHWHFWLRQ

Test Set 1 Test Set 2

Test Sets 1+2 Test Sets

1+2+3 Total Sensitivity (95% CI) Total Sensitivity (95% CI) Sensitivity (95% CI) Total Sensitivity (95% CI) n % n % % n % LAP 39 51.3 (35-68) 3 100 (29-100) 54.8 (39-70) 65 55.4 (43-68) 1-2 cm 22 54.5 (32-76) 1 100 56.5 - - > 2cm 17 47.1 (23-72) 2 100 52.6 - - Low grade 30 50.0 (31-69) 0 - 50.0 (31-69) - - High grade 6 50.0 (12-88) 3 100 (29-100) 66.6 (30-93) - - Tubular 9 44.4 (14-78) 0 - 44.4 (14-78) - - Tubulovillous 21 47.6 (26-70) 3 100 (29-100) 54.2 (33-74) - - Villous 5 60.0 (15-95) 0 - 60.0 (15-95) - - Serrated 4 75.0 (19-99) 0 - 75.0 (19-99) - - CRC 29 75.9 (57-90) 23 73.9 (52-90) 75.0 (61-86) 73 79.5 (68-88) Stages I-II 14 71.4 (42-92) 9 44.4 (14-78) 60.9 (39-80) 33 66.7 (48-82) Stages III-IV 15 80.0 (52-96) 14 92.9 (66-100) 86.2 (68-96) 40 90.0 (76-97) Stages I-II-III 22 81.8 (60-95) 19 68.4 (44-87) 75.6 (60-88) 58 79.3 (67-89) Low grade 23 69.6 (47-87) 18 66.7 (45-89) 68.3 (63-92) - - High grade 5 100 (48-100) 3 100 (29-100) 100 (63-100) - - Specificity (95% CI) Specificity (95% CI) Specificity (95% CI) Specificity (95% CI) n % n % % n % Controls (negative colonoscopy) 48 89.6 (77-97) 26 88.5 (70-98) 89.2 (80-95) 90 90.0 (82-95)

http://doc.rero.ch

(30)

7DEOH3RVLWLYHUDWHRIWKH0*0&DQG0*0&3DOJRULWKPVIRU RWKHUFRORUHFWDOOHVLRQVDQGGLVHDVHV MGMC MGMC-P Total Positive rate Positive rate n % % AP<1cm 67 29.9 28.4 Hyperplastic polyps 61 29.5 27.9 IBD 14 42.9 28.6 Other GI diseases 19 36.8 31.6 Inflammatory diseases 11 18.2 18.2

Hepatitis, Herpes, AIDS 10 20.0 10.0

(31)

7DEOH  6SHFLILFLW\ DQG VHQVLWLYLW\ RI WKH 0*0&3 DOJRULWKPIRU&5&DQGODUJH$3GHWHFWLRQ

Test Sets 1 + 2 Test Sets 1 + 2 + 3

Total Sensitivity (95% CI) Total Sensitivity (95% CI) n % n % LAP 42 52.4 (37-69) 65 52.3 (40-65) 1-2 cm 23 52.2 (31-73) - -> 2cm 19 52.6 (31-79) - -CRC 52 75.0 (61-86) 73 78.1 (67-87) Stages I-II 23 56.5 (35-77) 33 60.6 (42-75) Stages III-IV 29 89.7 (73-98) 40 92.5 (80-98) Stages I-II-III 41 70.7 (55-84) 58 74.1 (61-85) Specificity (95% CI) Specificity (95% CI) n % n % Controls (negative colonoscopy) 74 91.9 (83-97) 90 92.2 (85-97) 

http://doc.rero.ch

Références

Documents relatifs

[r]

*ORPHUXODUGLVHDVHUHQDO IDLOXUHDQGRWKHUGLVRUGHUVRI NLGQH\DQGXUHWHU0DODGLHV JORPpUXODLUHVLQVXIILVDQFH UpQDOHHWDXWUHVDIIHFWLRQVGX

Dans son char, enveloppé d'une épaisse nuée noire, Phaéton n'avait qu'un seul désir : que ce cauchemar se termine au plus vite!. Plutôt la mort que cette terreur

[r]

• Réaliser un montage “amplificateur non inverseur” branché en entrée sur un générateur de tension réglable, et branché en sortie sur un résistor “de charge” réglable,

Castagnède, Mesure des constantes élastiques du bois à l'aide d'un interféromètre ultrasonore numérique et leur optimisation.. Mark, Etude d'un champ de

[r]

[r]