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”
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 2
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 3
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.”
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 4
Patient Credentialing Meeting Patients Where They Are With Their Care Empoweringpeopletobeeffectiveintheirownself-management…◦ AssessmentDomains◦ Knowledge*◦ Skills◦ Performance
◦ AchievementLevels◦ Beginner◦ Proficient◦ Advanced
*Psychometricallyvalidated
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 5
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 6
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 7
*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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 9
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 10
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…
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 12
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.
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 13
Center for Translational Medicine / DoD Partnership Vision and Goals " Vision:Forgeaconsortiumofleadingpublicandprivatesectorhealthleaderstoprovideaholisticend-to-endPrecisionMedicineDemonstration
" Goal:DemonstrateimmediatereadinessbenefitsandcostsavingsfromarapidPrecisionMedicinepilotfocusedonkeymilitaryandpublichealthissues
" Expectedoutcomes:" BetterCare,Access" ImprovedHealth" LowerCost
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 14
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.
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 15
CPIC Resources PGxtoolsforpractice:◦ Guidelines◦ Genes-Drugs◦ Alleles◦ Publications◦ Meetings◦ Resources◦ Informatics
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 16
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.
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 17
CPIC Levels CPICassignsCPIClevelstogenes/drugswith
1. PharmGKBClinicalAnnotationLevelsofEvidenceof1A,1B,2Aand2B,or2. APharmGKBPGxlevelforFDA-approveddruglabelsof“actionablepgx”,“genetictesting
recommended”,or“genetictestingrequired”,or
3. BasedonnominationtoCPICforconsideration.
ProcessforassigningCPIClevels
Levelsforgenes/drugs
ProcessforprioritizingCPICguidelines
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 18
Level Definitions for Genes/Drugs
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 19
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…
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 20
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 21
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 22
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?
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 23
NEW
Imagine What Might Be Possible …in Patient-Centered, Team-Based Care if… PGxData(MinimumDataSet)
+
CurrentMedicationList
+
ActionableGuidelines(e.g.,CPICA/B)
…availableatthepoint-of-care
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 24
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
21-Jun-18 COPYRIGHT©2018,APHAFOUNDATION. 25