I nc ide nta l F inding s in Ge no mic s: E thic a l fra me wo - - PowerPoint PPT Presentation

I nc ide nta l F inding s in Ge no mic s: E thic a l fra me wo rks a nd pra c tic a l c ha lle ng e s

Mildre d Cho Ce nte r fo r I nte g ratio n

• f Re se arc h On

Ge ne tic s and E thic s Stanfo rd Ce nte r fo r Bio me dic al E thic s

E thic a l a nd po lic y fra me wo rks

 E

thic a l fra me wo rks

 Princ iple s: risk b e ne fit c a lc ulus, a uto no my  Re spo nsib ilitie s: dutie s a nd re la tio nships  Co nte xts: re se a rc h, c linic a l, pub lic he a lth  Po lic y fra me wo rks & drive rs

 Va lue s in tra nsla tio n

 Dia g no stic te c hno lo g y a sse ssme nt

 E

vide nc e -b a se d vs. te c hno lo g ic a l impe ra tive

 Da ta priva c y, o wne rship a nd

ma na g e me nt

 Ope n so urc e vs. c o mme rc ia l inte re sts

Co nse nsus o n e thic a l fra me wo rk in g e ne tic te sting

 Be st inte re st o f pa tie nt  Re po rting o nly info rma tio n fo r whic h the re

is e vide nc e o f b e ne fit

 Be ne fit o utwe ig hs risks  Re spe c ting rig ht to kno w  Re spe c ting rig ht no t to kno w

Co nse nsus o n e thic a l fra me wo rk

 Wilson & Jungne r

(1968) Princ iple s and Prac tic e o f

Sc re e ning fo r Dise ase .

 IOM (1994) Asse ssing Ge ne tic Risks: I

mplic atio ns fo r He alth and So c ial Po lic y

 ASHG (1995) Po ints to Co nside r: E

thic al, L e g al, and Psyc ho so c ial I mplic atio ns o f Ge ne tic T e sting in Childre n and Ado le sc e nts

 NIH T

ask F

• r

c e on Ge ne tic T e sting (1997) Pro mo ting Safe

and E ffe c tive Ge ne tic T e sting in the Unite d State s

 AAP (2000) Ne wb o rn Sc re e ning : A Blue print fo r the F

uture

 ACMG (2012) Po ints to Co nside r in the Clinic al Applic atio n

• f Ge no mic Se q ue nc ing

 AAP/ ACMG (2013) E

thic al and Po lic y I ssue s in Ge ne tic T e sting and Sc re e ning o f Childre n

E thic a l shift

 ACMG 2005 Ne wb o rn Sc re e ning : T

• ward a

Unifo rm Sc re e ning Pane l and Syste m

 Be ne fit to fa mily a nd so c ie ty

 Ale xa nde r & va n Dyc k 2006 A visio n o f the

future o f ne wb o rn sc re e ning

 Pe diatric s 117: S350-S354  Cha ng ing “the do g ma tha t it is a ppro pria te to

sc re e n o nly fo r c o nditio ns fo r whic h e f- fe c tive tre a tme nt a lre a dy e xists ne e ds to b e c ha ng e d, b y br

• ade ning the c onc e pt of be ne fit fro m

sc re e ning fo r the c hild to inc lude the fa mily.”

E thic a l shift

 “…de pe nds o n de ve lo ping a ne w

sc re e ning te c hno lo g y tha t c o nta ins c o sts b y sc r

e e ning for vir tually all tar ge t c onditions with one te st syste m.”

E thic a l shift

 Be st inte re st o f fa mily  De -e mpha sizing a uto no my  ACMG 2013 Re c o mme ndatio ns fo r

I nc ide ntal F inding s in Clinic al E xo me and Ge no me Se q ue nc ing

Re c o mme nda tio ns

 T

• a c tive ly se a rc h fo r spe c ifie d muta tio ns

in spe c ifie d

 T

• no t o ffe r the pa tie nt a pre fe re nc e

a b o ut re c e iving re sults

 T

• no t limit re po rting b y a g e

Arg ume nts

 Clinic ia ns a nd la b o ra to ry pe rso nne l ha ve

fiduc ia ry duty to pre ve nt ha rm

 Amo unt o f g e ne tic c o unse ling ne e de d to

disc uss unre la te d c o nditio ns “o ve rwhe lming ”

 Ma sking a na lysis wo uld b e “unwie ldy” a nd

pla c e s a n “unre a listic b urde n” upo n la b o ra to rie s

 Pa tie nts ha ve the rig ht to de c line c linic a l

se q ue nc ing

Arg ume nts

 Re spe c t fo r pa re nta l de c isio n-ma king

a b o ut c hildre n’ s he a lth

 Pa re nts o f c hildre n unde rg o ing

se q ue nc ing do no t ha ve “re a dy a c c e ss” to se q ue nc ing in o rde r to o b ta in pe rso na l risk info rma tio n

Ana lo g ie s

 Ana lo g y to physic ia n e xa mining c a rdia c

a nd re spira to ry func tio n in a pa tie nt c o mpla ining o f dig e stive pro b le ms

 Ana lo g y to ra dio lo g ist re po rting o n

a b no rma l finding s no t indic a te d in prima ry re a so n fo r sc a n

Ca ve a t

 “T

he Wo rking Gro up a c kno wle dg e d tha t the re wa s insuffic ie nt e vide nc e a b o ut b e ne fits, risks a nd c o sts o f disc lo sing inc ide nta l finding s to ma ke e vide nc e - b a se d re c o mme nda tio ns.”

F a c to rs in a sse ssing risk a nd b e ne fit

 Virtua lly no a ssura nc e o f a na lytic a l va lidity  F

DA a nd NI ST de ve lo ping sta nda rds

 Wide va rie ty o f pla tfo rms with diffe ring re sults  Diffic ult to a sse ss c linic a l va lidity  I

nte r-la b va ria b ility in inte rpre ting pa tho g e nic ity

 I

nte rpre ta tio n limite d b y a c c e ss to da ta - pro prie ta ry da ta b a se s

Re g a rdle ss o f pa te nta b ility  T

e sting lo w risk po pula tio ns - lo w PPV

F a c to rs in a sse ssing risk a nd b e ne fit

 I

nte rpre ta tio n is re so urc e -inte nsive a nd c o stly

 I

nc ide nta l finding s a misno me r in g e no mic s

I

n re se a rc h b e c a use it is e xplo ra to ry

I

n c linic a l se tting b e c a use ra w da ta must a c tive ly b e inte rpre te d, b y g ro ups with b ro a d e xpe rtise

 So me finding s re q uire e xte nsive fo llo w-

up to inte rpre t inc luding g a the ring o the r sa mple s a nd c o nduc ting studie s

F a c to rs in a sse ssing risk a nd b e ne fit

 F

• llo w up c a re is c o stly a nd must b e

inc lude d in c o st b e ne fit a nd c o st e ffe c tive ne ss c a lc ulus

 Oppo rtunity c o sts  Co sts o f disc rimina tio n, e g insura nc e

Co nc lusio ns

 De c isio ns a b o ut the limits o f o r o b lig a tio ns

to re po rt inc ide nta l finding s sho uld b e b a se d o n e sta b lishe d e thic a l princ iple s a nd e vide nc e

 T

e c hno lo g y ha s c ha ng e d b ut e thic a l princ iple s pe r se ha ve no t

 E

vide nc e a b o ut ha rms, b e ne fits la c king