beyond the hype-developing, implementing and sharing pharmacogenomic clinical decision support

7/28/2019 Beyond the Hype-Developing, Implementing and Sharing Pharmacogenomic Clinical Decision Support

1/31

Beyondthe

Hype:

Developing,

Implementing,andSharing

PharmacogenomicClinical

DecisionSupport


2/31

PanelOverview

Clinicaldecisionsupport(CDS)inthe

electronichealth

record

(EHR)

will

play

a

crucialroleinmaximizingtheuseof

pharmacogenomicdataoverapatients

lifetime.

Lessonslearnedatinnovatorsitesmustbe

organizedand

shared

among

care

settings

and

EHRvendors


3/31

Objectives

Compareandcontrastearlyadopters

approachto

develop

and

implement

CDS

for

pharmacogenomics.

ReviewtheroleoftheEHRandCDSinfacilitatingthetestingapanelofdrug

metabolismgenes

among

appropriate

patient

populations.


4/31

Objectives

ReviewtheuseofactiveandpassiveCDSfor

pharmacogenomicsat

innovator

sites,

includingdrug/genepairsinuseand

frequencyofuse.

IdentifychallengesandbarrierstodevelopingandimplementingCDSfor

pharmacogenomics.

DescribestrategiesforsharingCDSacrosscaresettingsandEHRplatforms.


5/31

Speakers

1. JoshF.Peterson,MD,MPH

VanderbiltUniversity

School

of

Medicine,

Nashville

TN

2. JamesM.Hoffman,PharmD,MSSt.JudeChildrensResearchHospital,Memphis,TN

3. RobertR.

Freimuth,

PhD

MayoClinic,Rochester,MN

4. Mark

Hoffman,

PhD

CernerCorporation,KansasCity,MO

BriefQuestions

after

each

presenter

and

panel

discussion

at

the

end


6/31

BeyondtheHype:

Developing,Implementing,

and

Sharing

PharmacogenomicClinicalDecisionSupport

AMIASummit

on

Translational

Bioinformatics

March18,2013

JamesM.Hoffman,Pharm.D.M.S.

AssociateMember,PharmaceuticalSciences

St.JudeChildrensResearchHospitaland

PAAR4Kids,NIHPharmacogenomicsResearchNetwork


7/31

Objectives

Identifystepsandresourcesfordevelopment

andimplementation

of

pharmacogenomic

CDS

Describe

key

design

choices

of

passive

and

activepharmacogenomicCDSatSt.Jude

Identifyopportunitiestofacilitatebroader

adoptionof

pharmacogenomic

CDS


8/31

ASimplifiedModelofCDS

Implementation

Discovery

KnowledgeBase

Governance,

Design,and

Implementation

Evaluation

Asuseofpharmacogenomicsexpands,

howcanweacceleratetheprocess?

Forpharmacogenomics,establish

GenotypingApproach

to

provide

data

for

eachpatient


9/31

DevelopmentandImplementationof

PharmacogenomicCDS

at


10/31

FDAasaknowledgebasefor

pharmacogenomicsand

CDS

FDAmaintainsatabledrugswith

pharmacogenomic informationin

their

labels

Over115drugsintableasofFeb2013!

FDAusespharmacogenomicswhenevaluatingandcommunicatingdrugsafety

Codeineprominent

current

example

http://www.fda.gov/drugs/scienceresearch/researchareas/pharmacogenetics/ucm083378.ht

m


11/31

CPICsInherentframework:

Ifyou

had

the

genotype

result,

how

should

youactonit?

Consistentwithpreemptive,arraybased

genotyping

CPICincludes

Over

60

clinicians

and

scientists,

from

33institutions

12countries

Observers

from

NIH

and

FDA


12/31


13/31

St.Jude

Family

Advisory

Council

(Alicia

Huettel

et

al)

Greatdiversityofopinion

FromwhyareyoutellingmethistoIwantto

decidewhen

this

goes

in

record

Highlevelofinterest

HelpedtoputtogethereducationalDVD

Remainengagedinprotocol

http://beta.web.st

jude.org/news/rel

ling/jl3404_PGEN4Kids.html


14/31

PharmacogeneticsOversight

Committeeat

St.

Jude

Representativesfromacrossthehospital

Meetsquarterly

Approves

Gene/drugpairs

for

implementation

decisionsupportmessagesandmechanisms

ReportstoPharmacyandTherapeutics

Committee


15/31

TimelineforClinicalGenotypingandCDSatSt.Jude

2000 2007 2009 2011

Crewsetal.Amer JHealthSyst Pharm 2011;68(2):14350.

SOME

ActiveCDS

Comprehensive

Passiveand

ActiveCDS


16/31

AbilitytogenotypeatlotsoflocionCLIA

approvedarray

is

coming here

and

allows

for

preemptivegenotyping

AffyDMET

array:

over

1million

features

to

interrogate1900polymorphismsin225genes

Outstandingconcordancewithorthogonal

methodsof

genotyping

(Fernandez

et

al,

CPT,

2012)

Forthesamemoneywespendon2genes,we

caninterrogate

225

genes

Makespreemptivegenotypingapossibility


17/31

PG4KDS :CLINICAL

IMPLEMENTATION

OFPHARMACOGENETICSatST.JUDE

Goal:migratepharmacogenetictestsfrom

laboratory(arraybased)intoroutinepatient

care,to

be

available

preemptively

18 months May 20th 2011 to Jan 30th, 2013Firstpt enrolled Currentclinic n

08Jun2011 Neurooncology 165

10

Jun

2011 BMT 2004May2012 Aftercompletiontx 4

21May2012 HIV 92

24Apr2012 Radiationoncology 29

24Jun2011 Solid tumor 189

27May2011 Leukemia 277

08Nov2012 NonmaligHematology 180

Total 956


18/31

BothpassiveandactiveCDSare

essentialfor

pharmacogenomics

PassiveCDS

Concisegenespecificinterpretationsmustbe

providedto

clinicians

throughtheEHR

Theinformationwillbe

posted

once

per

gene Manycombinationsexist,

andsotheprocessmustbe

automated

ActiveCDS

Preandposttestalerts

Highriskphenotypes

automaticallyplaced

on

the

problemlist

Interruptivepointofcarealert

triggered

when

problem

list

entryandhighriskdrug

prescribingcombine

Drugspecificinformation

provided

Keydesigndecisionsmadeduringdevelopmentand

implementation:


19/31

CYP2D6 LookupReferenceTable

Diplotype

Linked

to

Priority

and

Phenotype

DiplotypeinMilli(Result) Phenotype Priority EMRFlag(Color)

(*5/*5)0N PM Priority Abnormal

(*1/*1)1N EM Routine Normal(*2/*2)1N EM Routine Normal

(*1/*1,*1/*9,*9/*9)1N EMorIM Routine Normal

(*41/*41)1N IM Routine Normal

(*17/*17,*17/*40,*40/*40)1N IMorPM Indeterminate Abnormal

(*4/*4)1N PM Priority Abnormal

(*1/*1)2N EM Routine Normal



(*1/*2)3N UM Priority Abnormal





20/31


21/31

PharmacogeneticstabaddedtoEMR;

allclinicallyeligiblegenotypesareentered,

alongwith

agene

specific

consult

and

letter

to

patient


22/31


23/31


24/31

***PHARMACOGENETICS CONSULT FOR***

*CYP2D6 GENOTYPE*

Sample for CYP2D6 Genotype Obtained:

9/22/2011

PG4KDS CYP2D6 Genotype Result: (*1/*1)2N

Based on the genotype result this patient ispredicted to be an extensive (normal)

metabol izer of CYP2D6 substrates.

This result signifies that the patient has two

copies of a wild-type (normal function)

allele. The expected phenotype suggeststhat there is no reason to selectively adjust

the dose of most medications (including

codeine) that are metabolized by the

CYP2D6 enzyme pathway. The diplotype

result equates to a CYP2D6 activ ity score of

2. For more information about specific

medications metabol ized by CYP2D6, please

go to www.stjude.org/pg4kds.

Comments: none

Jane Smith, Pharm.D., pager 1234

Phenotype

Assignment (6 versions)

Diplotype

Interpretation (32 versions)

Dosing

Recommendations (6 versions)

Act ivi ty Score (11 versions)

EducationalLink

Deconstruct the

consult intosections; scalableto add additionaldiplotypes

Hickset

al

(CPT

2012)


25/31

TPMTPrepharmacogenetictestwarning:at

pointof

care

to

prescriber


26/31

Highriskdiplotypestranslatedto

phenotype,automatically

populated

intoProblemListofEMR

Why use the problem list?

- Experience- Useful when building other active CDS

- Flexible

- Incorporate outside result

- Emerging drug information

- Can incorporate other data (e.g. dose)

- Scalable and generalizable to others


27/31

Posttest:whenahighriskdrugcollideswithahighrisk(priority)

genotype,active

CDS

alerts

fire

at

point

of

care

Patients with high-risk genotype:e.g. CYP2D6 UM or PM;CYP2C19 PM;TPMT heterozygote

Patients with high-risk drugs:

e.g. codeine, amitriptyline;clopidogrelazathioprine

35customdrugandphenotype

specificrules

implemented:

TPMTwiththiopurines (azathioprine,thioguanine,andmercaptopurine)

CYP2D6 withvariousdrugs(codeine,tramadol,amitriptyline,fluoxetine,andparoxetine)


28/31

Ifahighriskdrugisorderedforapatientwitha

highrisk

genotype,

MD

gets

awarning

in

the

EHR


29/31

Standardsneeded

fordiagnostic

terms

TPMT- St Jude EMR Terms

TPMT - Normal Activity

TPMT - Intermediate Activity

TPMT - Possible Intermediate Activity

TPMT - Low or absent Activity

TPMT SNOMED CT CodeThiopurinemethyltransferasedeficiency

vs

PROGRESSFromLOINC!!!


30/31

Suggestionsforsuccessful

pharmacogenomicCDS

UseknowledgebasessuchasCPICprovide

clinicalcontent

DevelopbothpassiveandactiveCDS

PretestandposttestactiveCDSmaybeneeded

Remainmindfuloftheriskforalertfatigue

Posttestalertsinterruptcliniciansonlywhena

highrisk

drug

is

ordered

on

apatient

with

ahigh

riskphenotypeontheproblemlist

ActiveCDScanbebasedontheproblemlist


31/31

SJPharmaceutical Kelly Caudle St.Jude PGRN

KrisCrews Paula

Condy Scott

Howard Josh

Peterson

KevinHicks LisaWalters JerryShenep TeriKlein

GillianBell TerriKuehner ChingHonPui AlanShuldiner

ChristianFernandez SheriRing AlbertoPappo JulieJohnson

Cyrine

Haidar Shannon

Gibbs Sima

Jeha Russ AltmanShaneCross MargaretEdwards AdityaGaur DickWeinshilboum

JamesHoffman UlrikeReiss Wolfgang Sadee

NancyKornegay SJBiostatistics AliciaHuettel DanRoden

PamMcGill ChengCheng MelissaHudson

EmilyMelton DeqingPei AmarGajjar

AlejandroMolinelli InformationSciences

ColtonSmith MCW DonBaker

WilliamEvans Uli Broeckel Keith Kunkel

MarkWilkinson Rachel Lorier Andras

Sablauer

WenjianYang Alexander Stoddard RajeshParashuran

DavidZhao

beyond the hype-developing, implementing and sharing pharmacogenomic clinical decision support

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