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

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

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 (1968 ) Princ iple s and Prac tic e o f  Wilson & Jungne r 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 e sting (1997) Pro mo ting Safe  NIH T ask F or c e on Ge ne tic T 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 o 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 o 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 oade 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 o a c tive ly se a rc h fo r spe c ifie d muta tio ns in spe c ifie d  T o 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 o 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 o 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