Public Health Genomics: Reaching the Summit

JanLowery,PhD,MPHCOCenterforPersonalizedMedicine

Objectives • Definegenomicsinthecontextofpublichealth• Describeexamplesofhowgenomicscanbeintegratedintopublichealthprograms

• Discusstheroleofpublichealthintheemergingfieldofpersonalizedmedicine

Step6

Step5

Step4

Step3

Step1

MountGenome

Step2

Step1:ChartourPath

What is our path? 10 essential PH functions:

• Monitorhealthstatus•  Diagnoseandinvestigatehealthproblemsandhazards•  Inform,educateandempowerpeopleabouthealthissues.• Mobilizecommunitypartnershipstoidentifyandsolvehealthproblems.•  Developpoliciesandplansthatsupportindividual/communityhealthefforts.•  Enforcelawsandregulationsthatprotecthealthandensuresafety.•  Linkpeopletohealthservices;assureprovisionofcarewhenotherwiseunavailable.•  Assureacompetentpublichealthworkforce.•  Evaluateeffectiveness,accessibilityandqualityofpopulation-basedhealthservices.•  Researchfornewinsightsandinnovativesolutionstohealthproblems.

(https://www.cdc.gov/publichealthgateway/publichealthservices/essentialhealthservices.html)

Step 2: Check our gear

PH Infrastructure, Tools and Resources

•  Registries•  Birth,death•  Cancer•  Otherchronicdisease

•  Population-basedsurveys•  BRFSS,PRAMS,provideraccess

•  Preventionservices•  Cancerscreening(breast,cervical,colon)

•  WiseWomenprogram:CVD•  DiabetesandCVDmanagement•  Clinicalguidelines

•  PHworkforcetraining•  ClinicalQualityImprovementProgram

•  Accesstoprimarycareproviders,communityclinics,hospitals,localPH

•  PHCommunications

•  Multi-mediaplatforms•  Publicawarenesscampaigns

•  CommunityPartnerships•  Cancercoalition,localPH,communityclinics,Medicaid/Medicare,hospitals

•  Evaluationstaffandexpertise

Step 3: Comply with rules

Recommendations for Genomic Applications in PH

•  1997,CDCOfficeofPublicHealthGenomics(OPHG)established•  OPHGprovidestimelyandcredibleinformationfortheeffectiveandresponsibletranslationofgenome-baseddiscoveriesintopublichealth&healthcare

•  2012,OPHGestablishedsystemforevaluating‘readiness’ofgenomicapplicationsbasedonavailableevidence(categorizedintoTiers1-3)

•  3Tier1Applications=readytogo.‘Havesignificantpotentialforpositiveimpactonpublichealthbasedonavailableevidence-basedguidelinesandrecommendations’

•  FDAlabelrequiresuseoftesttoinformchoiceordoseofadrug•  FDAclearedorapprovedcompaniondiagnosticdevice•  CMScoverstesting•  Clinicalpracticeguidelinesbasedonsystematicreviewsupportstesting

https://www.cdc.gov/genomics/implementation/toolkit/tier1.htm

Tier 1:Hereditary breast and ovarian cancer

• Womenshouldbescreenedforfamilyhistorythatmaybeassociatedwithanincreasedriskforpotentiallyharmfulmutationsinbreastcancersusceptibilitygenes(BRCA1orBRCA2).Womenwithpositivescreeningresultsshouldreceivegeneticcounselingand,ifindicatedaftercounseling,BRCAtesting.

•  2005/13USPSTFGuideline(https://www.uspreventiveservicestaskforce.org/)• HealthyPeople2020Objective(https://www.healthypeople.gov/2020/topics-objectives/topic/genomics)

Tier 1: Lynch syndrome (LS)

• AllpeoplewithnewdiagnosedcolorectalcancershouldbeofferedgenetictestingforLStoreducemorbidityandmortalityinrelatives.

•  2009,EGAPPrecommendation(https://www.nature.com/articles/gim20095)• HealthyPeople2020Objective(https://www.healthypeople.gov/2020/topics-objectives/topic/genomics)

Tier 1: Familial Hypercholesterolemia • CascadescreeningusingcholesteroltestingwithorwithoutDNAanalysisshouldbeconductedonrelativesofaffectedpersonswithFHinordertoidentifypreviouslyunknowncasesofFHandprovidethosepeoplewithlife-savingtreatment

• NICErecommendation,2013(https://www.nice.org.uk/guidance/qs41)

Tier 1 Applications affect ~2 million Americans • PopulationHealthImpact:

•  HBOC:mutationprevalence=1in300to1in500;accountfor5-10%ofbreast,15%ovariancancers;40-80%lifetimerisk;increasedriskforpancreatic,prostatecancer

•  Lynchsyndrome:mutationprevalence=1in300;3-5%ofcolorectalcancer;upto80%lifetimerisk;increasedriskforendometrial,smallbowel,liver,ovarian,pancreatic

•  FH:mutationprevalence=1in250to1in500;5xriskofcoronaryheartdisease;earlyheartdiseaseandheartattack

• Mostpeopleatrisk,donotknowit•  Evidenced-basedinterventionsexisttoreduceriskandmorbidity

Step 4: Forge the trail

Integrate Tier 1 Applications into PH Practice

• Background:In2003;CDCOPHGbeganfundingafewstatestoenhanceimplementationofTier1applicationsintoPH

•  Michigan,Oregon,Washington,Georgia,Utah,Connecticut,Colorado•  3Strategies:Education,PolicyandSystemsChange,Surveillance•  FocusonHBOCandmorerecentlyLSandFH•  2014OPHGdevelopedtool-kitforstatestoadoptthesestrategies

https://www.cdc.gov/genomics/implementation/toolkit/tier1.htm

Colorado Experience: Getting started

• BuildinfrastructureatCDPHE•  HireGenomicsCoordinator•  Establishsharedstaffingmodelwith:cancerregistry,comprehensivecancer,healthinformatics,communications,programevaluation

•  Establishexternalpartnerships

•  UnivColoradoCancerCenter•  COSchoolofPublicHealth•  CancerCoalition/FamilyHistoryTaskForce•  CommunityAdvisoryCommittee•  Healthcaresystems

Colorado Experience: Education Goals:§  Increasepublicawareness

o  website,socialmedia,video§  Increaseproviderawarenessand

knowledgeabouthereditarycancer

o  webinars,presentationstoprovidersandprofessionalsocieties

o  In-persontraining:CancerGenetics:

WhyItMattersforPrimaryCarePractice

www.cocancergenetics.org

Gene Video

(https://www.youtube.com/watch?v=jN_jGoHmjZc&t=186s)

Colorado Experience: Policy and Systems Change

• Bi-directionalreportingpilot

•  Familyhistoryscreening

•  LStumortesting

Bi-directional Reporting

• Goal=identifycancersurvivorsatriskforHBOC/LSandincreasereferralsforgeneticservices

Centralcancerregistry

Hospitaltumorregistry

GeneticsReferral

RunalgorithmtoIDat-riskcancersurvivors

Notifyproviders/patients;referforgeneticservices

CheckpatientEMRforreferral/testingstatusSTOP:useforqualityimprovementpurpose

Bi-directional Pilot Results

Institution1 Institution2 Institution3 Allinstitutions

Totalnumbercases

Numberreferredand/ortested

Totalnumbercases

Numberreferredand/ortested

Totalnumbercases

Numberreferredand/ortested

Totalnumbercases

Numberreferredand/ortested

Breastcancer 42 28(66.7%) 294 96(32.5%) 308 282(91.5%) 644 406(63%)

Ovariancancer 4 4(100%) 55 23(41.8%) 87 78(89.7%) 146 105(72%)

Coloncancer *5 *4(80%) *65 *15(23.8%)

91 65(71.4%) *168 *90(54%)

Uterinecancer 7 6(85.7%)

*Combinedcolonanduterinecancer

Family History Screening

Goal=facilitateimplementationoffamilyhistoryscreeningtoolinto primarycareclinics

SurveyofcommunityclinicsinCOtoassesscurrentpractices:

23%

62%

69%

Third-degree relatives

Second-degree relatives

Relative's age at diagnosis of cancer

Provider discretio

n

Unknown

Genetic testing service

Referralpracticesforgenetics**Mostclinicsdonotcollectadequatefamilyhistorytoreferpatientsforscreeningorgenetics

Familyhistoryroutinelycollected

LS Tumor Testing

•  Surveyed44Coloradohospitalstoassesscurrentpractices•  79%reportedthattheyscreenallcoloncancers•  54%haveawrittenpolicyforuniversalLynchscreening(ULS)•  Fewerruralhospitalsarescreening

Nextsteps:• DevelopinformationaboutULSimplementationforhospitals• Developreportcardsforhospitalsusingdatafromcentralcancerregistrydata(MSI,IHCforcolonandendometrialtumors)

Colorado Experience: Surveillance • Hereditarycancerburden:Centralcancerregistry

•  AlgorithmtoidentifysurvivorsatincreasedriskforHBPC/LSbasedonguidelines•  New**addedfieldsfor‘referredforgeneticcounselingand/ortesting’toabstract

• Utilizationofgeneticservices:AllPayorClaimsdata

• Prevalenceofcancerfamilyhistoryandreferraltogenetics;familyhistorycommunication;screeningcomplianceamonghighrisk:

•  BRFSSandPRAMssurveys•  Added6questionstoBRFSS,2016and2018

Hereditary Cancer Burden in Colorado (per NCCN guidelines)

Syndrome/SpecificCriteriaPeoplemeetingcriteria Peoplemeetingcriteria'exclusively'N % N %

HBOCBreastcancer<=50 32375 45.8% 27022 38.2%Twobreastcancerprimaries 8704 12.3% 5320 7.5%

Breastcancer<=60thatistriplenegativeforER/PR/Her2 720 1.0% 241 0.3%Malebreastcancer 662 0.9% 543 0.8%Ovariancanceratanyage(epithelial,non-mucinous) 13303 18.8% 12267 17.4%Metastaticprostatecancer 7692 10.9% 7666 10.8%AshkenaziJewishdecentwithbreast,ovarianorpancreaticcanceratanyage 319 0.5% 174 0.2%Breastandpancreasanyage 407 0.6% 263 0.4%

LynchSyndromeCRC<50 6177 8.7% 5536 7.8%

CRCatanyagethatisMSIunstableorMMRgenedeficient 514 0.7% 358 0.5%Endometrial<50 2580 3.7% 2318 3.3%EndometrialcaatanyagethatisMSIunstableorMMRgenedeficient NAyet NAyet

CRCwithmetachronousorsynchronousLScancer* 1987 2.8% 802 1.1%EndometrialcawithmetachronousorsynchronousLScancer* 1216 1.7% 152 0.2%Synchronous/MetachronousCRC 2697 3.8% 2017 2.9%

AvailabilityofcancergeneticscounselorsinCO

Distributionofcancercases:Breastcancer<50,ovariancancer

Distributionofcancercases:colon<50,uterinecancer<50

BRFSS Results

•  FamHxbreast/ovarianca<50: 11%•  FamHxcolonca<60: 6%

•  IfYES,referredforgenetics: ~60%

Haveyoueverspokenwithyourmedicalprovideraboutyourfamilyhistoryofcancer?

Step 5: watch the weather

MountGenome

DTC

DTC

DTC

DTC

Watchtheweather

Forgethetrail

Followtherules

Checkgear

Chartpath

Changing Climate: emergence of DTC genetic tests and personalized medicine •  >12millionpeopleinUShaveusedDTCsand#saregrowing

•  PrecisionMedicineInitiative–AllofUs•  Biobanks•  Growingdisparitiesinawarenessandknowledge(AmJPrevMed2018;54:6:806-13)

• WhatistheroleofPH?

•  Inform,educateandempower•  InterpretingDTCtestresults–‘no’newsisnotnecessarily‘good’news•  Provideperspective:weightofgenomicsvsotherriskfactors,e.g.obesity

•  Linkpeopletoservices;assureprovisionofcarewhenotherwiseunavailable•  Establishcentralresourceforgeneticsprovidersaccessibletoall

•  Assureacompetentpublichealthworkforce•  NeedforimprovedgenomicliteracyamongPHworkers,providers,students

•  PHmustbeinvolved!!

Step 6: Finish strong

Sustainability: how do we assure that genomics stays integrated into PH practice? • Problem:

•  OutsideofOPHGgrants,nodirectmoneyfor‘genomics’forstatePH•  MajorityofPHfundingisfederal(CDC);small%isstatemonies

•  Solutions?

•  Specifictax,liketobaccotaxinCO.Whatwouldbetaxed?•  Extendpartnershipswithnon-for-profitgroups,e.g.Foundations•  Establishpublic-privatepartnerships,e.g.withtestinglaboratories?•  Re-directexistingfunding(fromstateandCDC)tointegrategenomicsacrossmultiplePHprograms;e.g.cancerregistry,compcancer,cancerscreeningprograms,chronicdiseaseandwellnessprograms

ReachingtheSummit

MountGenomeFinishstrong

Watchtheweather

Forgethetrail

Complywithrules

Checkgear

Chartpath

MountGenome

Finishstrong

Watchtheweather

Forgethetrail

Complywithrules

Checkgear

Chartpath

Acknowledgements CCGATeam•  EmilyFields,MS,CGC,ColoradoGenomicsCoordinator•  RandiRycroft,MSPH,formerDirectorCOCentralCancerRegistry(CCCR)•  JohnArend,MPH,currentDirectorCCCR•  LisaKu,MS,CGC,GeneticCounselor,UCCancerCenter•  LisenAxell,MS,CGC,GeneticCounselor,UCCancerCenter•  ShannonLawrence,ProgramEvaluation,CDPHE•  KristinMcDermott,ProgramEvaluation,CDPHE

• CDCOPHG,Grant#DP14-1407

Thankyou!