ASAPJune2018 Presentations 03 Bluml...Benjamin M. Bluml, RPh, APhA Foundation Matthew Rutledge, Rxight/MD Labs INTEGRATING PHARMACOGENETIC TESTING IN REAL-WORLD PRACTICE 2014 Stats;

IMPACT: Pharmacogenetics

IMProving America’s Communities Together

WEST PALM BEACH, FL ● THURSDAY, JUNE 21, 2018

BENJAMIN BLUML, RPH SENIOR VICE PRESIDENT, RESEARCH AND INNOVATION

21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 1

Improve health by inspiring philanthropy, research and innovation that advances

pharmacists’ patient care services

Innovative Practice Model Designs with Consistently Improved Outcomes

!  Adherence !  Alzheimer’s

!  Diabetes !  Depression !  Hyperlipidemia

!  Hypertension

!  Osteoporosis

Our Research and Innovation Axioms

Do the right things well.

Structure. Process. Outcomes.

Align the Incentives, Improve the Outcomes, Control the Costs.

“The best way to predict the future is to invent it.” – Alan Kay

Convene

Pilot

ScaledDemonstration

Model

Refinemen

t

Idea

Continuous

Quality

Improvement

IMProvingAmerica’sCommunitiesTogether

NationalImplementation

…“IncubatingCareInnovation”


Net Annual Savings in Chronic Disease "  The Asheville Project: $1,622 - $3,356

"  Patient Self-Management Program: $918 "  Diabetes Ten City Challenge: $1,079 "  Project ImPACT: Depression: $983

Creating the Basis for a Preferred Future


Immunizations

Diabetes

APhAFoundation.org/our-work

Where we’re going… Best way to get there…  Empoweredpatients

 Increasedcollaboration Enhancedsafety Improvedoutcomes

 Reducedcosts

 Putpatientsfirst Optimizemedicationuse

 Improvecommunication

 Manageinformation

 Increasecollaboration

“Patient-centered,team-basedcareisthebestwaytoinventapreferredfuture.”


Patient Credentialing Meeting Patients Where They Are With Their Care  Empoweringpeopletobeeffectiveintheirownself-management…◦ AssessmentDomains◦ Knowledge*◦ Skills◦ Performance

◦ AchievementLevels◦ Beginner◦ Proficient◦ Advanced

 *Psychometricallyvalidated


DIABETESCVHEALTH

Evaluation/planningunderway:-PilotingcollaborationwithPCMHs-Potentialinclusionwith-NeweMeasuresindevelopment-Healthplanbenefitsintegration

IMPACT Database Explorer Meeting Providers Where They Are With Their Data  InnovativeDataManagementSystemsdesignedto…◦ BuildontheFoundation’ssuccessfulpatient-centered,team-basedcareresearchandinnovationhistory◦ Aggregatekeyinformation(assessment,clinical,economic,andhumanisticdata)formeaningfulevaluationanduse◦ Providecliniciansandresearcherswithintegrateddatadashboardsandreportingutilizingsecuretechnologyinfrastructure◦ Accommodateuseofinformationacrossthecliniciancarecontinuumutilizingappropriate,de-identified,aggregateddisplayframeworkconsistentwithAPhAFoundationprivacyandconfidentialityprinciples


American Pharmacists Association Pharmacist Distribution by Geography*

18%

28%35%

18%1%

APHAMEMBERSNortheast Midwest South

West U.S.Territories

19%

23%

38%

19%1%

PROFESSIONNortheast Midwest South

West U.S.Territories


*Source:APhADatabase(Nov-14),USBLS(May-13)

Our Research and Innovation 20+ Years of Imagining What is Possible…

21-Jun-18 8

• 1996–Point-of-Caretestingincommunitypharmacies?

• 1999–At-riskscreening,identification,andreferral?

• 2004–11NationalPharmacyorgsagreeonMTM?

• 2006–Monitoringdepressionstatusqualitatively?

• 2009–HomeBP/Activitymonitoringforhypertension?

• 2010–Translateemployersuccessestounderserved?

• 2014–3DprintingofcustomizedmedicationsatPOC?

• 2016–ArmingproviderswithregistrydataatPOC?

• 2017–Processworkflowoptimizationsforprevention?

• 2018–PGxdecisionmakingintegratedintoMTM?

• CholestechLDXs/Point-of-CaretestingnowacrossUS

• HRAs,practicelevelscreeningscommonlyusednow

• DefinitioninFederalregulations,MTMisastandard

• PHQ-9/PHQ-2assessmentsnowfrequentlyutilized

• Enhancedaccountabilityanddiscoveryinpatientcare

• Evidencethatindividualized,team-basedcareworks

• Proofofconcept/FDAapprovalforprintingtablets

• Improvedidentification/resolutionofunmetneeds

• Federallysupportedmodelinmulti-state/yeargrant

• Activeworkonresourcesw/PGxtoenhancesafeuse

APhAFoundation.org/our-work

Imagining What Might Be Possible …Pharmacogenomics, Team-Based Care  15-Mar-10◦  CoriellInstituteforMedicalResearch/APhAFoundationNIHResearchProposalCollaboration

◦  ReinvigoratingtheBiomedicalResearchCommunitybyforginganewcollaborativerelationshiptostudytheroleofthepharmacist

 24-Feb-11◦  APhAFoundation/Coriell–InstituteCouncilofAppliedPharmacogenomicshttp://cpmc.coriell.org

◦  First12pharmaciststrainedaspartofapharmacistscoachingteamwithintheCoriellPersonalizedMedicineCollaborative

 24-Dec-12◦  APhAFoundationCommitteetoAdvancePGxinPharmacyPracticehttp://www.APhAFoundation.org/pharmacogenomics

◦  StrategicPlanforAdvancingPharmacogenomicsinPharmacyPractice;outlinedkeyareasoffocus:

◦  Research/Evidence◦  Practice/BusinessModels

◦  Standards/Policies◦  Education/Awareness/Advocacy◦  HealthInformationTechnology


Imagining What Might Be Possible …3D Printing, PGx, Nanotechnology  16-Sep-14◦  APhAFoundationassertionthatwewouldsee3Dprintinginthefuturecapableofproducingmedicationscustomizedtoanindividual’sgenomeatthepointofcare.Furthermore,imaginewhatmightbepossibleifcomponentscouldbeaddedtothose“printedmedications”toprovidelive,real-timemonitoring.

 25-Oct-14◦  ProofofconceptreportedinMedicalNewsToday--UniversityofCentralLancashireproducedanew3Dprinterthatcan“print”atabletwithaprecisequantityofmedicinesuitableforadministrationtopatients.

 1-Dec-14◦ MITreportinTechnologyReview,“3-D-PrintingBio-ElectronicParts,”indicatedthatresearcherswereabletoprintlightemittingdiodesforthefirsttimewithnew“inks”thatcontainsemiconductors.

 OtherConvergingInnovation◦ UniversityofCaliforniaSanDiegoscientistshavepresentedNanoscale3Dprintingandtissueengineeringapplications◦  Swissresearchershaveproducedwirelessremotemonitoringofglucoselevelsusingnanostructuresandbiosensors

  Pharmacist.com,22-Jan-15.http://www.pharmacist.com/advancing-pharmacogenomics-pharmacy-practice


Invited Presentation at CIAPM, Los Angeles, 26-Aug-16

Joshua N. Liberman, PhD, Sutter Health Benjamin M. Bluml, RPh, APhA Foundation Matthew Rutledge, Rxight/MD Labs

INTEGRATING PHARMACOGENETIC TESTING IN REAL-WORLD PRACTICE

2014Stats;SutterHospitals24MedicalNetworkPhysicians5,000Network/AffiliateEmployees49,381HospitalDischarges190,054EmergencyRoomVisits797,057HomeCare–HealthVisits483,649HomeCare–HospiceVisits263,885OutpatientVisits11,121,733

% of Population for which Particular Drug is Ineffective…


38% ANTI-DEPRESSANTS 40%

ASTHMA DRUGS

43% DIABETES

DRUGS

50% ARTHRITIS

DRUGS 70% ALZHEIMER’S

DRUGS 75% CANCER DRUGS

Efficiently integrating PGx testing into the selection and treatment process

" ResearchtoemployaverybroadandcomprehensivePGxpanel" 60targetalleles" 18genes" Potentiallycoveringover200medicationsfrom14+therapeuticcategories

" Patientmedicationpreferenceswillbecategorizedusingred/yellow/greenflaggingsystem

" Apatientgeneticconsultationor“PersonalizedMedicationReview™(PMR)”fromatrainedpharmacistincludedwitheverytest

" Recommendationscommunicatedtoprescribingphysician(s)foraction.


Center for Translational Medicine / DoD Partnership Vision and Goals " Vision:Forgeaconsortiumofleadingpublicandprivatesectorhealthleaderstoprovideaholisticend-to-endPrecisionMedicineDemonstration

" Goal:DemonstrateimmediatereadinessbenefitsandcostsavingsfromarapidPrecisionMedicinepilotfocusedonkeymilitaryandpublichealthissues

" Expectedoutcomes:" BetterCare,Access" ImprovedHealth" LowerCost


FederalHealthProvider

MajorHealthProviders

NEW

CPIC  TheClinicalPharmacogeneticsImplementationConsortium(CPIC®)isaninternationalconsortiumofindividualvolunteersandasmalldedicatedstaffwhoareinterestedinfacilitatinguseofpharmacogenetictestsforpatientcare.

 Onesignificantbarriertoimplementationofpharmacogenetictestingintheclinicisthedifficultyintranslatinggeneticlaboratorytestresultsintoactionableprescribingdecisionsforaffecteddrugs.

 CPIC’sgoalistoaddressthisbarriertoclinicalimplementationofpharmacogenetictestsbycreating,curating,andpostingfreelyavailable,peer-reviewed,evidence-based,updatable,anddetailedgene/drugclinicalpracticeguidelines(https://cpicpgx.org/publications/).

 CPICguidelinesfollowstandardizedformats,includesystematicgradingofevidenceandclinicalrecommendations,usestandardizedterminology,arepeer-reviewed,andarepublishedinaleadingjournal(inpartnershipwithClinicalPharmacologyandTherapeutics)withsimultaneouspostingtocpicpgx.org,wheretheyareregularlyupdated.


CPIC Resources  PGxtoolsforpractice:◦ Guidelines◦ Genes-Drugs◦ Alleles◦ Publications◦ Meetings◦ Resources◦ Informatics


CPIC Guidelines  CPICguidelinesaredesignedtohelpcliniciansunderstandHOWavailablegenetictestresultsshouldbeusedtooptimizedrugtherapy,ratherthanWHETHERtestsshouldbeordered.AkeyassumptionunderlyingtheCPICguidelinesisthatclinicalhigh-throughputandpre-emptive(pre-prescription)genotypingwillbecomemorewidespread,andthatclinicianswillbefacedwithhavingpatients’genotypesavailableeveniftheyhavenotexplicitlyorderedatestwithaspecificdruginmind.CPIC’sguidelines,processesandprojectshavebeenendorsedbyseveralprofessionalsocieties.

 EachCPICguidelineadherestoastandardformat,andincludesastandardsystemforgradinglevelsofevidencelinkinggenotypestophenotypes,howtoassignphenotypestoclinicalgenotypes,prescribingrecommendationsbasedongenotype/phenotype,andastandardsystemforassigningstrengthtoeachprescribingrecommendation.TheSOPforguidelinecreationhasbeenpublishedinCurrentDrugMetabolism:IncorporationofPharmacogenomicsintoRoutineClinicalPractice:ThePharmacogeneticsImplementationConsortium(CPIC)GuidelineDevelopmentProcess.TheCPICauthorshipguidelinesareupdatedregularly.


CPIC Levels  CPICassignsCPIClevelstogenes/drugswith

1.  PharmGKBClinicalAnnotationLevelsofEvidenceof1A,1B,2Aand2B,or2.  APharmGKBPGxlevelforFDA-approveddruglabelsof“actionablepgx”,“genetictesting

recommended”,or“genetictestingrequired”,or

3.  BasedonnominationtoCPICforconsideration.

 ProcessforassigningCPIClevels

 Levelsforgenes/drugs

 ProcessforprioritizingCPICguidelines


Level Definitions for Genes/Drugs


CPICLevel ClinicalContext Levelofevidence StrengthofRecommendation

A Geneticinformationshouldbeusedtochangeprescribingofaffecteddrug

Preponderanceofevidenceishighormoderateinfavorofchangingprescribing

Atleastonemoderateorstrongaction(changeinprescribing)recommended.

B Geneticinformationcouldbeusedtochangeprescribingoftheaffecteddrugbecausealternativetherapies/dosingareextremelylikelytobeaseffectiveandassafeasnon-geneticallybaseddosing

Preponderanceofevidenceisweakwithlittleconflictingdata

Atleastoneoptionalaction(changeinprescribing)isrecommended.

C Therearepublishedstudiesatvaryinglevelsofevidence,somewithmechanisticrationale,butnoprescribingactionsarerecommendedbecause(a)dosingbasedongeneticsmakesnoconvincingdifferenceor(b)alternativesareunclear,possiblylesseffective,moretoxic,orotherwiseimpracticalor(c)fewpublishedstudiesormostlyweakevidenceandclinicalactionsareunclear.MostimportantforgenesthataresubjectofotherCPICguidelinesorgenesthatarecommonlyincludedinclinicalorDTCtests.

Evidencelevelscanvary Noprescribingactionsarerecommended.

D Therearefewpublishedstudies,clinicalactionsareunclear,littlemechanisticbasis,mostlyweakevidence,orsubstantialconflictingdata.Ifthegenesarenotwidelytestedforclinically,evaluationsarenotneeded.

Evidencelevelscanvary Noprescribingactionsarerecommended.

Tables for Genes/Drugs  AsofMay,2018thereare49levelADrug/Genepairsandover350total…


Gene Drug Guideline CPICLevel PharmGKBLevelofEvidence PGxonFDALabel CPICPublications(PMID)HLA-B abacavir https://cpicpgx.org/guidelines/guideline-for-abacavir-and-hla-b/ A 1A Testingrequired 22378157;24561393HLA-B allopurinol https://cpicpgx.org/guidelines/guideline-for-allopurinol-and-hla-b/ A 1A 23232549;26094938CYP2C19 amitriptyline https://cpicpgx.org/guidelines/guideline-for-tricyclic-antidepressants-and-cyp2d6-and-cyp2c19/ A 1A 23486447;27997040CYP2D6 amitriptyline https://cpicpgx.org/guidelines/guideline-for-tricyclic-antidepressants-and-cyp2d6-and-cyp2c19/ A 1A ActionablePGx 23486447;27997040UGT1A1 atazanavir https://cpicpgx.org/guidelines/guideline-for-atazanavir-and-ugt1a1/ A 1A 26417955TPMT azathioprine https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/ A 1A Testingrecommended 21270794;23422873DPYD capecitabine https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/ A 1A ActionablePGx 23988873;29152729HLA-A carbamazepine A 1A ActionablePGxHLA-A carbamazepine https://cpicpgx.org/guidelines/guideline-for-carbamazepine-and-hla-b/ A 1A ActionablePGx 23695185HLA-B carbamazepine https://cpicpgx.org/guidelines/guideline-for-carbamazepine-and-hla-b/ A 1A Testingrequired 23695185CYP2C19 clopidogrel https://cpicpgx.org/guidelines/guideline-for-clopidogrel-and-cyp2c19/ A 1A ActionablePGx 21716271;23698643CYP2D6 codeine https://cpicpgx.org/guidelines/guideline-for-codeine-and-cyp2d6/ A 1A ActionablePGx 22205192;24458010CACNA1S desflurane A 3ActionablePGxRYR1 desflurane A 3ActionablePGxDPYD fluorouracil https://cpicpgx.org/guidelines/guideline-for-fluoropyrimidines-and-dpyd/ A 1A ActionablePGx 23988873;29152729CYP2D6 fluvoxamine https://cpicpgx.org/guidelines/guideline-for-selective-serotonin-reuptake-inhibitors-and-cyp2d6-and-cyp2c19/ A 1A ActionablePGx 25974703UGT1A1 irinotecan A 2A ActionablePGxCACNA1S isoflurane A 3ActionablePGxRYR1 isoflurane A 3ActionablePGxCFTR ivacaftor https://cpicpgx.org/guidelines/guideline-for-ivacaftor-and-cftr/ A 1A Testingrequired 24598717TPMT mercaptopurine https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/ A 1A Testingrecommended 21270794;23422873CYP2D6 nortriptyline https://cpicpgx.org/guidelines/guideline-for-tricyclic-antidepressants-and-cyp2d6-and-cyp2c19/ A 1A ActionablePGx 23486447;27997040CYP2D6 ondansetron https://cpicpgx.org/guidelines/guideline-for-ondansetron-and-tropisetron-and-cyp2d6-genotype/ A 1A InformativePGx 28002639HLA-B oxcarbazepine https://cpicpgx.org/guidelines/guideline-for-carbamazepine-and-hla-b/ A 1A Testingrecommended 23695185CYP2D6 oxycodone A 2ACYP2D6 paroxetine https://cpicpgx.org/guidelines/guideline-for-selective-serotonin-reuptake-inhibitors-and-cyp2d6-and-cyp2c19/ A 1A InformativePGx 25974703CYP2C9 phenytoin https://cpicpgx.org/guidelines/guideline-for-phenytoin-and-cyp2c9-and-hla-b/ A 1A ActionablePGx 25099164HLA-B phenytoin https://cpicpgx.org/guidelines/guideline-for-phenytoin-and-cyp2c9-and-hla-b/ A 1A ActionablePGx 25099164G6PD rasburicase https://cpicpgx.org/guidelines/guideline-for-rasburicase-and-g6pd/ A 1A Testingrequired 24787449CACNA1S sevoflurane A 3ActionablePGxRYR1 sevoflurane A 3ActionablePGxSLCO1B1 simvastatin https://cpicpgx.org/guidelines/guideline-for-simvastatin-and-slco1b1/ A 1A InformativePGx 22617227;24918167CACNA1S succinylcholine A 3ActionablePGxCYP3A5 tacrolimus https://cpicpgx.org/guidelines/guideline-for-tacrolimus-and-cyp3a5/ A 1A 25801146CYP2D6 tamoxifen https://cpicpgx.org/guidelines/cpic-guideline-for-tamoxifen-based-on-cyp2d6-genotype/ A 1A 29385237CYP2D6 tamoxifen A 1ATPMT thioguanine https://cpicpgx.org/guidelines/guideline-for-thiopurines-and-tpmt/ A 1A ActionablePGx 21270794;23422873CYP2D6 tramadol A 1B ActionablePGxCYP2D6 tropisetron https://cpicpgx.org/guidelines/guideline-for-ondansetron-and-tropisetron-and-cyp2d6-genotype/ A 28002639CYP2C19 voriconazole https://cpicpgx.org/guidelines/guideline-for-voriconazole-and-cyp2c19/ A 1A ActionablePGx 27981572CYP2C9 warfarin https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/ A 1A ActionablePGx 21900891;28198005CYP4F2 warfarin https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/ A 1B 21900891;28198005VKORC1 warfarin https://cpicpgx.org/guidelines/guideline-for-warfarin-and-cyp2c9-and-vkorc1/ A 1A ActionablePGx 21900891;28198005CYP2C19 citalopram https://cpicpgx.org/guidelines/guideline-for-selective-serotonin-reuptake-inhibitors-and-cyp2d6-and-cyp2c19/ A 1A ActionablePGx 25974703CYP2C19 escitalopram https://cpicpgx.org/guidelines/guideline-for-selective-serotonin-reuptake-inhibitors-and-cyp2d6-and-cyp2c19/ A 1A ActionablePGx 25974703IFNL3 peginterferonalfa-2a https://cpicpgx.org/guidelines/guideline-for-peg-interferon-alpha-based-regimens-and-ifnl3/ A 1A 24096968IFNL3 peginterferonalfa-2b https://cpicpgx.org/guidelines/guideline-for-peg-interferon-alpha-based-regimens-and-ifnl3/ A 1A ActionablePGx 24096968IFNL3 ribavirin https://cpicpgx.org/guidelines/guideline-for-peg-interferon-alpha-based-regimens-and-ifnl3/ A 1A 24096968


Inventing a Preferred Future…

AligntheIncentives,ImprovetheOutcomes,ControltheCostsTM

Medication Use Quality & Safety

Patient Access to Needed Medications & Pharmacy Services

Interoperability of Pharmacy & Health Information Technology

Team-Based Care Contributions in Pharmacy Practice


HealthPromotion

" HealthRiskAssessment

" Immunizations

" OralHealth

" WellnessPrograms

HealthManagement

" Asthma

" CardiovascularDisease(Dyslipidemia,Hypertension)

" CoagulationDisorders" CongestiveHeartFailure" Depression" Diabetes" Osteoporosis

…allwithMTM

Selection Criteria: - High prevalence - High risk - High cost - Problem prone

Imagine What Might Be Possible …in Patient-Centered, Team-Based Care if… TogetherwemakePharmacogeneticdatatransferrableandusableincommunitypracticewithinthecontextofwell-establishedguidelines?

1.  Wouldtheworldbeabetterplaceifeachpatienthadanaccurate,up-to-datelistingoftheirmedicationsthattheywereabletosharewitheachhealthcareproviderateveryvisit?

Pharmacogeneticinformationisapatientcharacteristicthatisdifficulttotransferacrosscaresettings;notasinglenumbereasilyrecalledlikeheight,weight,orothermetrics…

2.  Isitpossibleanddoesitmakesensethatapharmacogeneticrecordwouldbeapartofacomprehensivemedicationrecord/listthatpatientscontrolandsharewiththeirhealthcareproviders?

3.  CouldwefacilitateoptimizedmedicationuseandtherapeuticdecisionmakingwithaWebService/APIthatallowshealthcareproviderstoaccesscontinuouslyupdatedCPICpharmacogeneticcontentatthepoint-of-care?


NEW

Imagine What Might Be Possible …in Patient-Centered, Team-Based Care if… PGxData(MinimumDataSet)

+

CurrentMedicationList

+

ActionableGuidelines(e.g.,CPICA/B)

…availableatthepoint-of-care


Convene

Pilot

ScaledDemonstration

Model

Refinemen

t

Idea

Continuous

Quality

Improvement

IMProvingAmerica’sCommunitiesTogether

NationalImplementation

NEW

Questions / Dialogue BENJAMIN M. BLUML, RPH [email protected]

SENIOR VICE PRESIDENT, RESEARCH AND INNOVATION


Documents

ASAPJune2018 Presentations 03 Bluml...Benjamin M. Bluml, RPh, APhA Foundation Matthew Rutledge, Rxight/MD Labs INTEGRATING PHARMACOGENETIC TESTING IN REAL-WORLD PRACTICE 2014 Stats;