from the human genome project to the nih precision medicine initiative

8/9/2019 From the Human Genome Project to the NIH Precision Medicine Initiative

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NIH Precision Medicine Initiative:Turning Discovery into Health

Gary H. Gibbons, M.D.Director

National Heart, Lung, and Blood Institute

National Press Foundation Precision Medicine MeetingMayo Clinic

Rochester, MN

May !, "#$


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NIH Precision Medicine Initiative (PMI) Overview and Implementation

Te PMI and te Nation!s Healt NH"#I $cienti%ic &ision %or PMI

NIH Precision Medicine Initiative %PMI&:Turning Discovery into Health


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'hat is the Precision Medicine ())roach*

(n e+erging a))roach to disease )revention,diagnosis and treat+ent

Considers the uniue genes and environ+ent o-

each )atient Provides the right treat+ent, at the right ti+e,

tailored to a )atient.s individual needs


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Precision Medicine

'oncept is not new Consider )rescri)tion eyeglasses, /lood trans-usions0

Pros)ects -or /roader a))lication raised /y recent advancesin /asic research, technology develo)+ent, geno+ics,)roteo+ics, +eta/olo+ics, 1HRs, Big Data, +Health, etc2

Rein-orced /y "# National Research Council re)ort

at is needed now Develo)+ent o- rigorous research )rogra+ to )rovide

scienti-ic evidence to turn conce)t into reality

Recruit+ent o- the /est and /rightest -ro+ +ulti)le disci)lines


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Current ())roach to Patient Care: (nnual Physical 13a+s and 4ne56i7e5Fits5(ll Care


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'hat I-* Diagnose and Treat an Individual PatientBased on Re-ined Patient Classi-ication and Treat+ent 4utco+es

Dianostic Precision ** +e%inin te 'linical 'lassi%ication o% Disease

Movin beyond ** One*$i-e*its*/ll!


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No +esponse0Deat/dverse 1vents/dverse 1vents



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No +esponse0Deat/dverse 1ventsNo +esponse0Deat



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'hat I-* Diagnose and Treat ( PatientBased on Re-ined Patient 6u/sets and Treat+ent 4utco+es

No +esponse0Deat/dverse 1ventsMar2ed +esponse to "owest Dose


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+itDr3

+itDose

+itTime

+itPerson

No +esponse0Deat/dverse 1ventsPrecision Medicine /pproac



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'hy No8* Recent Develo)+ents Ma9e ThisThe Right Ti+e

1lectronic Healt +ecordsPatient Partnersips

GenomicsTecnoloies

Data $cience


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PMI: Ti+ing is 1verything

Ten 4ears /o Now 5 6789(most recent data)

'ost o% $e:3encin a H3man

Genome"",###,### ### 5 $###

/mo3nt o% Time to $e:3encea H3man Genome " years ; day

N3mber o% $mart Pones inte ;nited $tates

+illion %;"


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Precision Medicine and 6tate o- the Anion

…. So tonight, I’m launching a new Precision

Medicine Initiative to bring us closer to curingdiseases like cancer and diabetes, and to give

all of us access to the personalized information

we need to keep ourselves and our families

healthier. e can do this.


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Cystic Fi/rosis and Precision Medicine Discovery 6cience that Trans-or+s Lives

CFTR gene identi-ied led to earlier diagnosisand i+)roved sy+)to+ +anage+ent

NIH5-unded research revealed CFTR +utations

resulting cellular actions that cause i+)airedlung -unction

Ne8 co+/ination thera)y targeting the +ostco++on CFTR +utations is trans-or+ing thelives o- )atients living 8ith CF2

CF e)ito+i7es the )ro+ise o- )recision +edicine discovery o- disease +echanis+s

re-ined diagnostic disease classi-ication individuali7ed, +utation5s)eci-ic thera)ies2


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8882nih2govE)recision+edicine


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PMI: ision and Goals

ision: Build a /road research )rogra+ toencourage creative a))roaches to )recision+edicine, test the+ rigorously, and,ulti+ately, use the+ to /uild the evidence

/ase needed to guide clinical )ractice2

Near Ter+: a))ly the tenets o- )recision +edicine to a+aor health threat 5 cancer

Longer Ter+: generate the 9no8ledge /ase necessary to+ove )recision +edicine into virtually all areas o- healthand disease


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PMI Pro)osed 6u))ort:President.s Budget F=

/ency = Million

NIHJ Cancer J Cohort

"##K#

>#

FD( #

4--ice o- the NationalCoordinator -or HealthIn-or+ation Technology

$

TOT/" =68>


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Longer ter+ -ocus on range o- health issues diseases Longitudinal cohort o- M or +ore (+ericans Mi3 o- e3isting cohorts and ne8 volunteers

NIH (dvisory Co++ittee to the Director PMI 'or9ing Grou))lanning +eetings

Building a consortiu+ o- cohorts cohort identi-icationand )artici)ant recruit+ent

Partici)ant engage+ent, data )rivacy, and novel 8ays o-

returning in-or+ation to )artici)ants Data collection including +o/ile health technologies

Data science, in-or+atics 1lectronic Health Records

NIH PMI Planning


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NIH (dvisory Co++ittee to the Director PMI 'G Pu/lic 8or9sho)s to in-or+ 6e)te+/er "#$ re)ort

NIH 8ith 'hite House, FD(, other agencies 6ee9ing in)ut -ro+:

-Potential )artici)ants

- Leaders o- current cohorts

- +Health technology develo)ers

- 1HR develo)ers

-Potential international )artners

Oct. 8, 678>?PMI la3nc@ %)ending F"#= a))ro)riations&

Near5Ter+ Ti+elines


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PMI Near Ter+: Cancer

())ly tenets o- )recision +edicine to cancer Build on The Cancer Geno+e (tlas %TCG(& that hascharacteri7ed geno+ic -eatures o- +any cancers in ,###)atients

Ase NCI clinical trials as +odels %e2g2, NCI5Match, Lung5M(P& to: Identi-y ne8 cancer su/ty)es and thera)eutic targets 6creen tu+ors -or certain geno+ic -eatures

(d+inister thera)ies s)eci-ic -or a geno+ic signature

Test )recision thera)ies, 8ith )rivate sector )artners

())ly these a))roaches to: ( 8ide s)ectru+ o- adult and )ediatric cancers

1arly stage to advanced disease


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PMI and Cancer Research:Possi/le Near5Ter+ ())lications

1valuating use o- liuid /io)sies -or non5invasive detectiono- tu+or res)onse

Anderstanding, counteracting develo)+ent o- resistance to

targeted thera)ies

Deter+ining )ros)ects o- co+/ination targeted thera)y /asedon individual tu+or geno+e analysis


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PMI Longer Ter+

Generate 9no8ledge /ase needed to +ove )recision +edicineinto the 8hole range o- health and disease

To reach this goal, the PMI 8ill su))ort research to: Create ne8 a))roaches -or detecting, +easuring, analy7ing a

8ide array o- /io+edical varia/les: +olecular, geno+ic,

cellular, clinical, /ehavioral, )hysiological, and environ+ental

Test these a))roaches in s+all, )ilot studies

Atili7e the +ost )ro+ising a))roaches in greater nu+/ers o-)eo)le over longer )eriods o- ti+e to collect data o- great value

to /oth researchers and )artici)ants


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PMI Longer Ter+:National Research Cohort of 1 million


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PMI National Research Cohort

'ill co+)rise: ? +illion A262 volunteers Nu+erous e3isting cohorts %+any -unded /y NIH&

Ne8 volunteers

Partici)ants 8ill /e: Centrally involved in design, i+)le+entation (/le to share geno+ic data, li-estyle in-or+ation, /iological

sa+)les all lin9ed to their electronic health records

'ill -orge ne8 +odel -or scienti-ic

research that e+)hasi7es: 1ngaged )artici)ants

4)en, res)onsi/le data sharing8ith )rivacy )rotections


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Meta5CohortNHLBI Core

Cohorts

To8ard Creating a National PMI Research Cohort:Potential Contri/ution o- 13isting NHLBI Cohorts

!"# in $amil% !ohorts&

Me'ican (merican

)ld )rder (mish

#iverse *+S

!linical !ohorts&

(sthma and !)P#


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National Research Cohort: Possi/le Ases

Facilitate research on thera)eutic sa-etyEe--icacyE+eta/olis+ 6tudy resilience /y -inding )eo)le 8ho should /e ill /ut aren.t

Ancover thera)eutic targets /y identi-ying rare variants)rotective against disease

Provide un/iased uantitative deter+ination o- ris9 4--er )o8er-ul test /ed -or:

Incor)orating )atient5re)orted outco+es

I+)roving utility o- 1HRs

1valuating 8ide array o- +Health a))lications


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'oort Datasets

Genomics

Proteomics0MetabolomicsiP$'s

#i Data* Ontoloies'omp3tational Models

Interate 5omics, clinicalimain, and ealto3tcome data in te

In%ormation 'ommons

#iorepositoriesImain

/st3te 'liniciansPenotypin

'hat I-* 'e Created a Large56cale Precision MedicineIn-or+ation Co++ons Re-lective o- 4ur Diverse Nation

Mobile Healt


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NIH Precision Medicine Initiative (PMI) Overview and Implementation

Te PMI and te Nation!s Healt NH"#I $cienti%ic &ision %or PMI

NIH Precision Medicine Initiative:Turning Discovery into Health

Th 1 - P i i M di i


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P3blic HealtImplementation

$cience

'ollaboration0+ole o%Ind3stry

'linical+esearc

#asic+esearc

Observational$t3dies

The 1+ergence o- Precision Medicine: ( NHLBI 6uccess 6tory (n Integrative ())roach

Fra+ingha+ Predictive Ris9 Factors

Intra+ural Research Progra+:Frederic9son, 6tadt+ans

Clinical Research:Tangier.s Disease%HDL Cholesterol&

Bro8n and Goldstein: No/el Pri7e%LDL Cholesterol&

NHLBI Trial: Lo8ering Cholesterol Cuts CHD Ris9

Roy agelos: 6tatins

alue o- Li-estyle Interventions

Di 6 i d P i i M di i


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+aal et al. 'irc3lation 6786A86BC697*698E

Discovery 6cience and Precision Medicine:"in2in "are F $mall $cale $cience and P3blic*Private Partnersips

'h t I-* ( l P i i M di i t (dd


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Incident 'ronic idney ail3re#y +ace

'hat I-* ())ly Precision Medicine to (ddressHealth Dis)arities

/stma*related1merency +oom &isits


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Reducing (sth+a Health Dis)arities: ( Multi5)ronged, Patient5Centric Precision Medicine ())roach

Movin beyond ** One*$i-e*its*/ll!

'omm3nity

1nvironment

amily

Individ3al-enetics

ehavior

!ulture

Schoolsualit%

Medical !are

Parks

*ealth

S%stems

Socio/!ultural

!onte't 0conom%

P i i M di i P ti t C t i C i C t t


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/stma Healt'are $ystem

Precision Medicine 55 Patient5Centric Care in Conte3t:The Inter)lay o- Genes, Behavior and 1nviron+ent

Ho+e

Co++unity

Fa+ily

Genetics

6chool

(llergens

'h t I-* B t di ti / t d / t d


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'hat I-* Best diagnostics, /est drug, /est dose /est outco+es -or all asth+a )atients

'linical $t3diesDo health dis)arities re-lect the rightdrugEright dose )ro/le+*J Best (-rican (+erican Res)onse to

(sth+a Drugs (#/+D)

Discovery o% Mediators0#iomar2ers (re there distinctive /iological -actors thatdrive racialEethnic dis)arities in asth+a*

/stma*related 1+ &isits

Patient*'entered/stma 'ontrol

1+)o8ering Patient 6el-5Manage+ent o- (sth+aJ Geos)atial air uality +onitor J Inhaler use alertsJ Patient5/ased /reathing testJ Patient5re)orted outco+es

mHealt

'h t I-* OB d th C . - R i l H lth I iti


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'hat I-* OBend the Curves. o- Racial Health Ineuities/y Precisely Predicting and Pre5e+)ting CD

CDC, @@=

Incident 'ronic idney ail3re

#y +ace

(-rican ancestry

6hared (-rican and1uro)ean ancestry

1uro)ean ancestry

Genomics

+isin Medicare 'osts

or 'D

Genomic /dmit3re /nalysisC/%rican /merican

-


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The 1cosyste+s o- Race5(ncestry Health Dis)arities:The O13)oso+e., Po)ulation History and Geno+ic ariation

1nvironment 01posome

Imm3ne De%ense $ystems

$ic2le 'ellD3%%y /ntien

G*B*PD

Infection

Host Genomic &ariation

'omm3nity

1nvironment

amily

Individ3al-enetics

ehavior

!ulture

Schoolsualit%

Medical !are

Parks

*ealth

S%stems

Socio/!ultural

!onte't 0conom%

'h t I-* R d P t 6 i A i 6t d C h t


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'hat I-* Re)roduce Past 6uccesses in Asing 6tudy Cohortsto Identi-ying Molecular Mediators o- Health Dis)arities

#iversit% in 1*+I/funded !ohorts& S!2 was associated with higher risk of

!3# in (frican (mericans.

JAMA. "#Q>"%"#&:"$5""$

(P4L Ri 9 i t - id F il i (- i ( i


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? $5-old increased ris9 o- 16D Hy)ertension, HI(N, 6CD "< o- (( have " ris9 alleles %GEG"& (lso "5-old increased ris9 o- CD

(P4L Ris9 ariant -or idney Failure in (-rican5(+ericans:Increased Ris9 o- Chronic idney Disease and CD

/ssociation o% Trypanolytic/po"8 &ariants wit idney

Disease in /%rican*/mericansG Genovese, D Fried+an0B

o)), 1 Pays, MR Pollac9

> (ugust "##

olu+e >"@, Issue $@@>

( T T ( T C C T T T ( ( ( ( T ( ( ( C T ( G ( ( T>=# >K# >!#

(

Start anti-

hypertensive andstatin treatmentat lower goal of130/80 in at-riskAPOL1/S!"arriers

Angiotensin#lo"kers in Afri"an-Ameri"ans withhigh-riskAPOL1/S!genotype

$ew dr%gstargetingmediatorsdownstream ofAPOL1 /S! toprevent kidneyfail%re

Parmacoenomics New terapies+is2 prediction

1volving Medicine as an In-or+ation 6cience:


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1volving Medicine as an In-or+ation 6cience: De+ocrati7ing Data5"5no8ledge in the Digital (ge

Partici)ant Patients: The Center o- the


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Partici)ant5Patients: The Center o- thePrecision Medicine Initiative

'illia+ 1lder r2 1+ily 'hitehead 1lana 6i+on

Melanie Ni3Hugh and

Beatrice Rienho--aree+

(/dul5a//arNoah and

(le3is Beery

'hat I-* 'e (cti el 1ngaged and 1+)o ereed the P /lic


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1estatchC 1na/les citi7ens tocontri/ute data trac9ing /ird

/ehavior in their area

Patients +ike MeC 1na/les)atients to share e3)erience9no8ledge and relationshi)s

-or change40) C 6lee)5'a9eCycle Citi7en Data

earable Mobile *ealth

2echnolog%&Patient5centric data generation

'hat I-* 'e (ctively 1ngaged and 1+)o8ereed the Pu/licin OCiti7en56cience. -or Healthier Co++unities


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Carla.s 6tory in "#!

olunteers to ta9e )art in NationalResearch Cohort

Cares -or her +other 8ho su--ered astro9e /ut -eels healthy2

Her DN( )ro-ile reveals a APOL1

variant that increases ris9 -or 9idneyand cardiovascular disease2

4--ered o))ortunity to try out8eara/le sensor to continuously

+onitor /lood )ressure, )hysicalactivity, diet, slee) )atterns, etc2 inds er blood press3re is

consistently i


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The Po8er o- +illion0


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uestions

from the human genome project to the nih precision medicine initiative

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