Three Models for RWE Use - MDEpiNet.org Homemdepinet.org/wp-content/uploads/03-Waters-Mike... ·...
Transcript of Three Models for RWE Use - MDEpiNet.org Homemdepinet.org/wp-content/uploads/03-Waters-Mike... ·...
EnhancingLaboratoryDataInfrastructuretoAccessReal-WorldEvidence(RWE)forinvitro
Diagnostics(IVDs):ThreeModelsforRWEUse
MichaelWaters,[email protected]
OfficeofInVitroDiagnosticsandRadiologicalHealth(OIR)CenterforDevicesandRadiologicalHealth(CDRH)
FoodandDrugAdministration(FDA)
MDEpiNet AnnualMeetingThursday,October19th,2017
2
Supporteffortstoharnessnon-traditionalinvitrodiagnostic(IVD)datasourcesto:• supportregulatorydecisionsforIVDsandmorethroughouttheTotalProductLifeCycle(TPLC),
• reduceburdenstothehealthcareecosystemand
• promotedevelopmentofinnovativesolutionstopublichealthchallenges.
SHIELDMission(SystemicHarmonization&InteroperabilityEnhancementforLabData)
3
WhatIVDsDo?
• Invitrodiagnostics(IVDs)productsare…intendedforuseindiagnosisofdiseaseorotherconditions...[21CFR809.3]
• Fundamentally,IVDs‘ask’aquestionofaspecimentakenfromahumanbody.
• Theresultthatfollowsisthe‘answer’tothatquestion.
4
Registries/EHRs:AccessingRWE
RWD≠‘bad/sketchy’dataRWE≠ lessevidence
‘FitforPurpose’Datamustbecomplete,consistent,accurate,andcontainallcriticaldata
elementsneededtoevaluateamedicaldeviceanditsclaims.
KEY:Coordination/Harmonization(Interoperability)
5
Multi-StakeholderIVDSemanticInteroperabilityEfforts
FDAengagedCDISCtoadvocateforLOINCinclusioninIVDsdevice
2013
2015
2016
• DraftGuidances:RWE,Interoperability,NGSDatabase• FDA/CDC/NLM/ONC/CMSLabDataInteroperabilityWkshp• LIVDLaunch• UDIforClassIIDevices
2017
• FinalGuidances:RWE,Interoperability,NGSDatabase• DraftofHL7&FHIRimplementationguide
2014
• Assemblyofmulti-stakeholderconsensusforumforlabdatasemanticinteroperability• UDIforClassIIIdevices
CDISC:ClinicalDataInterchangeStandardsConsortiumLOINC:LogicalObservationsIdentifiersNamesandCodesSNOMED:SystematizedNomenclatureofMedicineLIVD:IVDStructuredDataFormatCDC:CentersforDiseaseControlNLM:Nat’lLibraryofMedicineONC:OfficeoftheNat’lCoordinatorCMS:CenterforMedicareandMedicaidServicesNGS:NextGenerationSequencingHL7:Health-Level7FHIR:FastHealthcareInterchangeResource
• FDA/CDC/NLMLabDataInteroperabilityWkshp•WhitepaperforHarmonizationoflabdata• RecognizedStandards:LOINC,SNOMED• DraftofLIVD
6
SHIELDInfrastructure
Function Candidate Coding Elements (partiallist) Transmission Format
DescribeIVDdevice/methodtype
LOINC(LogicalObservationsIdentifiersNamesandCodes)
ComponentPropertyTimeSystemScaleMethod
Structured DataFormat-LIVD
DescribeIVDdevice/methodresult
SNOMED-CT(SystematizedNomenclatureofMedicine– ClinicalTerms)
DetectedNotDetectedInconclusiveTest NotCompleted
Structured DataFormat–LIVDII
UCUM(UnifiedCodeforUnitsofMeasure)
UnitsofMeasures(e.g.grams,etc.)
Structured DataFormat–LIVDII
Unique DeviceIdentification
UDI(FDA UniqueDeviceIdentificationSystem)
Device IdentifierElementsofUDI
Structured DataFormat-LIVD
AssociateddatapopulatedintoLaboratoryInformationSystems(LISs)canbequeried.FastHealthcareInterchangeResource(FHIR)implementationguideisnearcompletion.
7
OngoingSHIELDEfforts1. Developingtoolsfortheapplicationofsemanticstandardsin
structureddataformatsthrough:
• step-by-stepmanualdefininghowtomapLOINCtoIVDdevices
• Government/Industry/LaboratoryClinicalIVDSemanticInteroperabilityMeeting– ValueSets(LIVDII)
2. FDAisdevelopingregulatoryguidanceandinter-Office/Centerinfrastructuretodeterminehow/whenregulatorygradeReal-WorldEvidence(RWE)canbeleveragedinregulatorydecisions.
InvolvedStakeholders:FDA(CDRH,CDER,CBER),CDC,NIH,ONC,CMS,IVDManufacturers,EHRVendors,Laboratories,CAP,StandardsDevelopers,Academia
8
• LabsoperateundertheClinicalLaboratoryImprovementAmendments(CLIA)regulations
• CMSoverseeslabsthroughtheCollegeofAmericanPathologists(CAP)labaccreditationprogramLabsregularlyconductproficiencytestingofCAPpanelsandsubmitresultstoCAP(formosttests)
• LabsconformtoGoodLaboratoryPractices(GLP;21CFR58&42CFR493)
• Labshavetovalidateoff-labeluseandLaboratoryDevelopedTests(LDTs)
SomeNuancesUniquetoIVDs
9
• Lowprevalenceanalytes/patientpopulationsubgroups/rareendpoints/long-termoutcomes(e.g.,patient/healthcareproviderexperience)
• Bringingoff-labeluseon-labelandunderaQualitySystem(leveragingEHRdata;ObservationalStudies)
• LeveragingdatageneratedexternaltotheUnitedStates(leveragingOUSdatathatisfitforUS)
ThreeRWEUseCasesforIVDs*
*Existingexamplesandmodelsforfuture…
10
Real-WorldExperience
RWE Use Examples
Modificationofclaimsfromadjunctivetonon-adjunctivetousediagnosticfortreatmentdecisions
RWEExamples
EHR,SurveillanceData
RWEusedtosupportfalsenegativeratecalculations.
ObservationalStudies
Metaanalysis ofobservationalstudiesallowedacomparisonofsubjectdevicetoasimilardevice.
RWEcouldbeusedtosupportlowprevalenceanalyteclaims
EHRData
11
• Panelist’sclinicalexperiencewithcurrentoff-labelnon-adjunctiveuseofthemarketeddevice.
• Adiagnosticdevicewasapprovedbasedontraditionalclinicaltrialsandanalyticalstudies. • Directcommentsfromcurrentusersregarding
theirexperiencewithoff-labelnon-adjunctiveuseofthemarketeddeviceincluding:
− publiccommentsfrompatients,caregiversandothermembersofthecommunityimpactedbythedisease.
• PragmaticClinicalTrialwithpatientsusingtheadjunctiveandnon-adjunctivemethods.
• Sponsorsoughtshiftfrom: adjunctive usefollowedbyaninvasivemonitoringprocedureto: non-adjunctive use—whereCGMinformationcanbeuseddirectlytomakediabetestreatmentdecisions.
Real-WorldExperience
RWE Use Examples
Modificationofclaimsfromadjunctivetonon-adjunctivetousediagnosticfortreatmentdecisions
RWEExample1Background/Claim RWE
12
EHR,SurveillanceData
RWEusedtosupportfalsenegativeratecalculations.
RWE Use Examples
• LaboratoriesdevelopedandconductedscreeningtestsintheabsenceofanyFDAclearedorapprovedassay.
• Somestatesmandatediseasescreeningtestsduetothehighdiseasemortalityrate.
• Sponsorsoughtdenovoscreeningclaimtoaidinthediagnosisofdisease.
• Atraditionalpivotalstudywasconductedwiththenewdeviceincomparisontotheroutinelaboratoryscreeningtodeterminetruepositives.
• Itwasimpracticaltoperformconfirmatorytesting(orothersuitablefollow-up)onallnegativepatients.
• Thefalsenegative resultratewascalculatedbasedontheclinicalstatusofallpatientswhotestednegative.Publichealthlabsworkedwithdiagnosticcenterstocollectsurveillanceinformationtofollowuponallpatientsintheclinicalstudythatwerediagnosedwithanyofthescreenedconditionsandparticipated(falsenegatives).Therewerenofalsenegatives.
Background/Claim RWE
RWEExample2
13
• Clinicalperformanceforthistestwasassessedusingpublisheddata.Meta-analysesofpublishedstudiesofawiderangeofpatientpopulationsforseveraldiseaseswereconductedtocalculatelikelihoodratios(anestimateofhowthetestresultaffectsthechancesofacondition).
• Traditionalanalyticalstudieswereconductedalongwithstudiestodemonstrateusercomprehensionofthelabelingandtestresults.
• Sponsorsoughtdenovoclaimassesstheprobabilitythatapatientisatriskofdevelopingaseriesofdifferentdiseases.
Examples
Metaanalysis ofobservationalstudiesallowedacomparisonofsubjectdevicetoasimilardevice.
RWEExample3
ObservationalStudies
Background/Claim RWE
14
Examples
• Forsomeassays,thereisroutineclinicalfollow-upregardlessoftheresultsofthetest.
• Itmaybepossibletoreleasethedevicetomarketwithawell-qualifiedpresumptiveclaimforthedetectionofresistancegenesbasedonanalyticalstudiesandminimalclinicalinformationcollectedintrials.
• post-marketsusceptibility/resistancedataforalldetectedorganismscouldbecollectedalongwiththeobligatereferencemethodtobesubmittedinasecondapplicationtoremovethepresumptivequalifications.
RWEMockExample• Traditionalclinicaltrials
showthatgenestoidentifyaninfectiousorganismcanbedetected,butgenestoinferantibioticresistancearetoolowprevalence.
• Lowprevalenceanalytes/patientpopulationsubgroups/rareendpoints/long-termoutcomes canallbedifficultclaimstoattainanddramaticallyincreasethesizeofaclinicaltrial.
RWEcouldbeusedtosupportlowprevalenceanalyteclaims
EHRData
Background/Claim RWE
15
PotentialUseCaseCollaborations
Title: “AddingLightningSpeedtoClinicalLaboratoryDataAssessmentTools- ImplementationofAdd-OnToolsthatwillGenerateSemanticInteroperableLaboratoryDataOutputsfromClinicalTrials(CTs)andElectronicHealthRecords(EHRs)toexpediteanalyticalprocessesusingAcuteKidneyInjury(AKI)asaCaseStudy”Lead: FDA/CDER
Title: “EmergencyMedicineOpioidDataInfrastructure:KeyVenuetoAddressOpioidMorbidityandMortality”Lead: NIH/NIDA
16
Conclusions/Requests
• SHIELDimplementationcanunlockRWEsiloedindatarepositorieswhichmaybeleveragedinregulatorydecisions.
• OIRisengagingincross-centerandmulti-stakeholdereffortstoassistintheadoptionofsemanticinteroperabilitystandardsandstructureddataformats.
• Collaborationandsupportiscriticaltorealizingthebenefitsoftheseefforts.