Precision Medicine: The Big Picture

8/9/2019 Precision Medicine: The Big Picture

1/111

©2013 MFMER | 3309825-1

Alexander Parker, PhDProfessor of rolo!" and E#$de%$olo!"&e'$l$a and Dan &ar%$'hael Fa%$l" Asso'$a(e D$re'(or for (he &en(er for

)nd$*$d+al$ ed Med$'$ne

Pre'$s$on Med$'$nehe .$! P$'(+re


2/111

©2013 MFMER | 3309825-2

1/ ) a%, $(ho+( a do+ (, (he ar%-+# a'(/ he

dee# d$*es fro% (he hea*" h$((ers 'o%e la(er/2/ h$s (alk $s a o+( (he en($re f$eld of #re'$s$on

%ed$'$ne, so hen ) +se (he ord e ) do no(%ean Ma"o &l$n$'/

3/ ) $ll +se exa%#les fro% o+r #ra'($'e (o $ll+s(ra(eso%e ke" #o$n(s/


3/111

©2013 MFMER | 3309825-3

41 e( 6r$en(ed F$rs(7


4/111

©2013 MFMER | 3309825-

Personalized

Medicine

PrecisionMedicine

IndividualizedMedicine


5/111

©2013 MFMER | 3309825-5


6/111

©2013 MFMER | 3309825-

Discover and translate new opportunities forindividualizing the prevention, diagnosis and

treatment of disease through the use of the mostadvanced molecular and clinical technologies

available.


7/111©2013 MFMER | 3309825-:


treatment of disease through the use of the mostadvanced molecular and clinical technologies

available.


8/111


9/111©2013 MFMER | 3309825-9

6;, so ha(


10/111©2013 MFMER | 3309825-10

>h" do so%e #eo#le develop a particulardisease and o(hers donh" do so%e #eo#le respond to a particulartreatment and o(hers donh" do so%e #eo#le $ns$s( oncheering forDuke and not North Carolina?


13/111©2013 MFMER | 3309825-13

“This will revolutionizethe diagnosis,prevention and

treatment of most ,if not all, human

diseases.-.$ll &l$n(on, ?+ne 2000


16/111©2013 MFMER | 3309825-1

!" #ears

$% &illion


18/111©2013 MFMER | 3309825-18

&os( of >hole eno%e @e +en'$n!

?

B C1,000 (ose'uence one h+%an !eno%e


23/111©2013 MFMER | 3309825-23

“The waiting is thehardest part.

- o% Pe((", 1981


25/111

©2013 MFMER | 3309825-25

42 he Pra'($'e of Med$'$ne $sransfor%$n!7


26/111

©2013 MFMER | 3309825-2

The needs of the

patient come first.


27/111

©2013 MFMER | 3309825-2:

)nd$*$d+al$ ed Med$'$ne &l$n$'

Next GenerationSequencing

Expert Review andConsultation

Interpretive ReportGenerated

Individuali ed!edicine Consult

Sample Collection"#lood and$or Tissue% &ata Storage$'nal(sisReferral to I! Clinicand Consultation

1/ Referral- ased 2/ @(ar(s and Ends $(h Pa($en(


28/111

©2013 MFMER | 3309825-28


29/111

©2013 MFMER | 3309825-29

Ad*an'ed &an'ers

>e are +s$n! (he la(es( !ene($' se +en'$n!(e'hnolo!$es (o %o*e a a" fro% a“one size fits all

a##roa'h (o 'an'er (rea(%en(


30/111

©2013 MFMER | 3309825-30

6ne @$ e Does o( F$( All7• -"ear-old fe%ale $(h 'an'er $n her !all ladder

• &an'er has s#read (o her l+n!s

• er 'an'er d$d no( res#ond (o (hes(andard (hera#"

• @he enrolled $n a 'l$n$'al (r$al of a #oss$ le nedr+! for 'an'ers of (he !all ladder

• o res#onse7

• 6+( of o#($ons


31/111

©2013 MFMER | 3309825-31


32/111

©2013 MFMER | 3309825-32

)nd$*$d+al$ ed Med$'$ne &l$n$'Pro*$des a e o#e

• er on'olo!$s( 'ons+l(ed $(h (he Ma"o )nd$*$d+al$ edMed$'$ne &l$n$'

• ea% d$s'+ssed her 'ase and de(er%$ned she $s !ood

'and$da(e for !eno%$' se +en'$n!• ene($' &o+nselor %e( $(h #a($en( and her on'olo!$s( (oex#la$n #ros and 'ons

• Rese'(ed (he 'an'er and $sola(ed D A• (e'uenced the DN) from the tumor and our team

anal*zed it for “clues• )den($f$ed a %+(a($on $n a !ene 'alled F FR2

• @(ar(ed (ar!e(ed (hera#" a!a$ns( F FR2 +sed $n


33/111

©2013 MFMER | 3309825-33

+esponded to a drug we would have N - + thought

of using for this patient.


34/111

©2013 MFMER | 3309825-3


35/111

©2013 MFMER | 3309825-35


36/111

©2013 MFMER | 3309825-3

Challenges1. While the cost and time to sequence have

plummeted, the analysis still takes time and $$.

2. Sometimes find “hits” ut don!t kno" "hat theymean.

#. Sometimes find “hits” ut the e is no d ug togive.

%. Waiting too late, so should &ust se'uenceea lie (• )ssues of standa d of ca e

• *elevance(doing too ea ly+ Cance s evolve


37/111

©2013 MFMER | 3309825-3:

e are using the power of genomic

se'uencing to individualize cancertreatment.


38/111

©2013 MFMER | 3309825-38

D$a!nos($' 6d"sse"

>e are +s$n! (he la(es( !ene($' se +en'$n!(e'hnolo!$es (o f$nd ans ers for #eo#le $(h d$ff$'+l( (o

d$a!nose d$seases/


39/111

©2013 MFMER | 3309825-39

E*er"one Deser*es Ans ers7

• 23 "ear old %ale $(h (re%or, s#as($'$(" and %$ld$n(elle'(+al d$sa $l$("

• E#$sodes of +n'on(rolla le %o*e%en(s • @afe(" r$sk d+e (o falls• )%#a'( a $l$(" (o #erfor% a'($*$($es of da$l" l$*$n!• Mo*e%en(s kee# h$% a ake a( n$!h(

• &l$n$'al and !ene($' e*al+a($ons ere all$n'on'l+s$*e

• @een " B 5 e+rolo!$s(s a( %+l($#le $ns($(+($on


40/111

©2013 MFMER | 3309825- 0

) d$*$d l$ d M d$'$ &l$ $'


41/111

©2013 MFMER | 3309825- 1

)nd$*$d+al$ ed Med$'$ne &l$n$'Pro*$des a e o#e

• Ma"o e+rolo!$s( 'ons+l(ed $(h (he )nd$*$d+al$ edMed$'$ne &l$n$'/

• ea% d$s'+ssed (he 'ase and de(er%$ned (h$s #a($en( $s

!ood 'and$da(e for !eno%$' se +en'$n!/• ene($' &o+nselor %e( $(h #a($en( and fa%$l" (o ex#la$n#ros and 'ons/

• 6 (a$ned lood sa%#les fro% (he #a($en(, o(h $olo!$'al#aren(s and (he $olo!$'al +naffe'(edG s$s(er/

• (e'uenced the DN) from all four individualsanal*zed it for “clues .

• )den($f$ed a %+(a($on $n a !ene 'alled ;& A1 h$'h lead


42/111

©2013 MFMER | 3309825- 2


43/111

©2013 MFMER | 3309825- 3

-he patient has sta ted athe apy aceta/olamide0 to

help cont ol symptoms andimp ove his 'uality of life.


44/111

©2013 MFMER | 3309825-


45/111

©2013 MFMER | 3309825- 5

Challenges1. We don!t al"ays find the ans"e , sometimes

"e come up empty• u lished ates a e 234 of the time "e get a

ans"e in these cases

2. Can unea th a lot of “va iants of unkno"nsignificance”(mo e "o k(mo e $$$

#. 5oesn!t al"ays lead to a t eatment(no action"e can take.

%. 6ducating physicians a out the potential andho" to identify good candidates


46/111

©2013 MFMER | 3309825-

e are using the power of genomic

se'uencing to find answers for patients with difficult to diagnose diseases.


47/111

©2013 MFMER | 3309825- :


48/111

©2013 MFMER | 3309825- 8

43 Enhan'$n! he )%#a'(7


49/111

©2013 MFMER | 3309825- 9

Phar%a'o!eno%$'s

>e are +s$n! !ene($' se +en'$n! (e'hnolo!$es (o hel#!e( (he r$!h( dr+! (o (he r$!h( #a($en( a( (he r$!h( ($%e


50/111

©2013 MFMER | 3309825-50

r$al and Error A##roa'h


51/111

©2013 MFMER | 3309825-51

• *oughly 34 of all hospital admissions a e dueto adve se d ug eactions 75*s0.

• 75*s ange f om unpleasant(to fatal.

atient Safety


52/111

©2013 MFMER | 3309825-52

he #o er $n (a$lored (hera#e+($'s $s for+s (o sa" %ore 'learl" (o #a"ers,

#ro*$ders and #a($en(s7 H(h$s (rea(%en( $no( for e*er"one, +( $( $s for*ou


53/111

©2013 MFMER | 3309825-53


54/111

©2013 MFMER | 3309825-5


55/111

©2013 MFMER | 3309825-55

Challenge1. Seve al impo tant pha macogenetic

tests have een availa le fo manyyea s, and yet thei adoption in the clinic

emains uncommon.• 8 agmented health ca e system• 9o" use of 6:*s and difficulty integ ating

"ith e;isting 6:*s• System that does not e"a d p evention

2. 9ack of specific guidelines on ho" toad&ust medications on the asis of the

enetic test esults.


56/111

©2013 MFMER | 3309825-5


57/111

©2013 MFMER | 3309825-5:

The Clinical /harmacogenetics 0mplementation Consortium

ovide pee < evie"ed, updated, evidence< ased,f eely accessi le guidelines fo gene=d ug pai s

that "ill facilitate the t anslation ofpha macogenomic kno"ledge

f om ench to edside.


58/111

©2013 MFMER | 3309825-58

e are integrating genomic information

in to medical care to avoid giving patientsineffective and harmful drugs.


59/111

©2013 MFMER | 3309825-59

>$sh (here as %ore ($%e7


60/111

©2013 MFMER | 3309825- 0


61/111

©2013 MFMER | 3309825- 1


62/111

©2013 MFMER | 3309825- 2

-he 6me ging )ssue(

• eal(h" $nd$*$d+als ex#ress$n! $n(eres( $n (he +se !eno%$' %ed$'$ne >orr$ed >ell , eal(h" +(&+r$o+s , e('/G/

• Pred$'($*e eno%$'s

• # +n($l no e ere d$s'+ss$n! (h$s $n 'on(ex( of a

s#e'$f$' d$sease kno n or +nkno nG• o %o*$n! $n (o s'enar$o (ha( loses (ha( 'on(ex(

• Dee#er bioethical de a(e

• 0nsurance coverage for ser*$'e +nl$kel"


63/111

©2013 MFMER | 3309825- 3

thical and 1egal 0ssues?

Technolog* read*?

Cost? 0nsurance?

Direct to Consumer Testing?


64/111

©2013 MFMER | 3309825-


65/111

©2013 MFMER | 3309825- 5


66/111

©2013 MFMER | 3309825-

Pred$'($*e eno%$'s

>e are offer$n! a %en+ of !eno%$' ser*$'es (oaddress (he needs of heal(h" #a($en(s $n(eres(ed $n

accessing more information the* can use (oenhan'e (he$r heal(h and ellness/


67/111

©2013 MFMER | 3309825- :


68/111

©2013 MFMER | 3309825- 8

Disease Raises Many Questions…

What is my risk of developing Disease X?

If I have Disease X, what is the risk Iwill die from it?

If I chose a treatment for Disease X,what is the risk it won’t work for me?

If I undergo treatment, what is myrisk of side e ects?

Now more than ever, the answers


69/111

©2013 MFMER | 3309825- 9

For %os( h+%an d$seases,o+r !ene($'s se(s a ran!e of#oss$ $l$($es for +s7 +( $( s($ll

%a((ers ha( e do on a da" (oda" as$s/


70/111

©2013 MFMER | 3309825-:0

Risk isSubjective


71/111

©2013 MFMER | 3309825-:1

People want

difering levelso in ormation

about their risk


72/111

©2013 MFMER | 3309825-:2

The samein ormation

about risk canbe interpreted

very diferently


73/111

©2013 MFMER | 3309825-:3

e are moving forward in /redictive

2enomics.


74/111

©2013 MFMER | 3309825-:

Spiderman’s Uncle


75/111

©2013 MFMER | 3309825-:5

4 Don


76/111

©2013 MFMER | 3309825-:

4 Don ( For!e( (he F el for (h$sF$re7

Resear'h has and $ll 'on($n+e (o dr$*e (h$s


77/111

©2013 MFMER | 3309825-::

%o*e%en(7

ithout theabilit* to collect,

store and

anal*zebiologicalspecimens, the0ndividualized

3edicinemovement will

stagnate.

Investment in Specimen Storage


78/111

©2013 MFMER | 3309825-:8

p g

>?

Rochester ArizonaFlorida


79/111

©2013 MFMER | 3309825-:9


80/111

©2013 MFMER | 3309825-80

>e %+s( e!$n no (o #re#are for (he f+(+reJ e 'anno( a$( +n($l (he de(a$ls are kno n orf+ll" +nders(ood, nor 'an e ex#e'( (ha( o(hers

$ll address o+r 'on'erns or sol*e o+r#ro le%s7/David &. (chowalter, 3.D. 4!5678977:;Department of 3edical 2enetics


86/111

©2013 MFMER | 3309825-8


treatment of disease through the use of the mostadvanced molecular and clinical technologiesavailable.


97/111

©2013 MFMER | 3309825-9:

“I think there is aworld market formaybe fivecomputers.”

Thomas Watson,Chairman of IB , !"#$


100/111

©2013 MFMER | 3309825-100

) Couple Things to Take

1. 7dvances in genomic se'uencing a e at thehea t of the p ecision medicine movement.

2. We a e using ne" genomic se'uencing

technology to guide patient ca e(it!s a eality.#. -his is a t ansfo mative time( ut it is ea ly.

-he p omise is still out"eighing the eality.

%. -he e a e a num e of challenges andoppo tunities as "e move fo "a d.

3. @o one "ill accomplish this alone(a t ueteam effo t


104/111

©2013 MFMER | 3309825-10

g pthe future, full of interest, intriguing

be*ond m* power to describe>

-Dr/ >$ll$a% Ma"o


109/111

©2013 MFMER | 3309825-110

Challenge• Seve al impo tant pha macogenetic

tests have een availa le fo manyyea s, and yet thei adoption in the clinic

emains uncommon.• 8 agmented health ca e system• 9o" use of 6:*s• System that does not e"a d p evention

• 9ack of specific guidelines on ho" toad&ust medications on the asis of thegenetic test esults.


111/111

The Clinical /harmacogenetics 0mplementation Consortium

ovide pee < evie"ed, updated, evidence< ased,f eely accessi le guidelines fo gene=d ug pai s

that "ill facilitate the t anslation ofpha macogenomic kno"ledge

f om ench to edside

Precision Medicine: The Big Picture

Documents