MDEpiNet:AccomplishmentsandCapabilities

DanicaMarinac-Dabic,MD,PhD,MMSc,FISPE

Director,DivisionofEpidemiology,CDRH/FDAOnBehalfofMDEpiNet

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Summary• BriefMDEpiNet history/inthecontextofFDAvisionforthenationalsystem

• ScalableDomains• ExamplesofPartnerships/Capabilities:AStrategiclook

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2010 2011 2012 2013 2014 2015 2016 2017

MDEpiNetLaunch

InternationalConsortia(e.g.ICOR,ICCR)

Reports:• Planning

Board• MDEpiNet

RegistryTaskForce

• IMDRF

MDEpiNetMethodologyCenteratHarvard

MDEpNetScienceandInfrastructureCenteratCornell

MDEpiNetPartnershipCoordinatingCenteratDuke

Developandtestdrivenovelmethodsandscientificinfrastructurefordeviceevidencegenerationsynthesisandappraisalnationallyandinternationally

THEVISIONFORNATIONALSYSTEMLAUNCHEDFDA4- dayPublicMeetingDay1.LaunchofFDAstrategyDay2.MDEpiNetAnnualDays3-4.Registries

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MDEpiNet– QuickFacts• Over130partneringpublicandprivatesectororganizationsfromthedevice

ecosystemglobally(academia,professionalassociations,registries,industry,patientorganizations,healthsystemsandmore);

• Over100national/regionalregistriesfrom37countries;• 11NationalCRNsand4InternationalRegistryConsortia;• Over750clinicalexpertsacrossclinicalareas;• Over150methodologists(statisticians,epidemiologists,datascientists,

informaticians,healthcareresearchersandmore);• NationalandStateclaimsdata(e.g.CMS,NYSPARCS)• NationalandInternationalEHRs(e.g.PCORNet,Sentinel,VA,UK,Australia)• IntegratedHealthCareDeliverySystems(e.g.Kaiser)• Over60demonstrationprojectsincludingprojectswithPCORNetand

Sentinel• HighPerformanceIntegratedVirtualEnvironment(HIVE)collaborativespace

withpetabytesstoragespaceandanalyticaltools

Accesstoover30millionpatient/deviceencountersinregistries

Accesstohundredsofmillionsofclaimsrecords

www.fda.gov

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GlobalMDEpiNet

FutureMDEpiNetChapter

AcademicCenters

DataSources

ExistingMDEpiNetChapter

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RegistryDevelopmentNational/InternationalConsortiaDevelopment

ElectronicDeviceDataCapture(UDI)TaskForce-CoordinatedRegistryNetworks(CRNs)

PASSIONInitiative

ActiveSurveillanceComparativeEffectiveness

EvidenceSynthesisClaimsValidation

LinkagewithotherDataSourcesBigDataAnalytics

TranslationalEpidemiology

AugmentingRegistrieswithPROsandExplantAnalysisforPrecisionMedicine

AssessingMinimallyImportantDifference(MID)forimplantsPatientandFamilyEngagementCommittee

Patient-ledDevice/DiseaseSpecificRoundTable

Infrastructure

Methods

PatientEngagement

MDEpiNetWorkStreams

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ScalableDomainsofMDEpiNet

Tools

Infrastructure

Methodology

Partnerships

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Tools

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DataExtractionandLongitudinalTrackAnalysis(DELTA)

• DELTAsoftwarewasproducedbycollaborativeworkandsupportfromFDA,NLM,HarvardandLeahyatTufts.

• ItwasfirstvalidatedonoutcomesandclinicaltrialdatabasesandshowntoefficientlyidentifyverylowfrequencyeventsutilizinganarrayofBayesianandfrequentistinferencemethods.

• Itnowsupportsmultiplesimultaneousanalyses,trackingtheaccumulatingexperienceofmultipledevices,whilemonitoringmultipleindependentdatasetssimultaneously.

• Scalabilitydemonstratedthroughseriesofretrospectivethenprospectivestudies:

a. HealthCareSystemLevel- includingPartnersHealthcareinBostonb. Statelevel– includingMAAngioplastyRegistrysiteslinkedto

MassachusettsinpatientClaimsDB,andMAVitalStatisticsc. Nationallevel– NCDRCathPCIregistry(e.g.vascularclosuredevices).• BytheendoftheyearitisexpectedtobeinstalledinICDregistryandTVT

registry• Earlierthisyear– DELTAbecameanopensourceavailabletoall

stakeholdersatnocost.

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UDIasaKeyComponentofMDEpiNetMethodologyWork

RAPIDRegistryAssessmentofPeripheral

InterventionalDeviceshttp://mdepinet.org/rapid/

BUILDBuildingUDIIntoLongitudinalDataSetsforMedicalDeviceEvaluation

CARDIOVASCULARDEVICESSeehttp://mdepinet.org/build/

UDI– partofRealWorldData

UseDItopulldatafromGUDIDandauto-populatefields

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maxi-HIVE

location: White Oak /CDRH HPCstorage: ~2 Petabytescpu:3000 cores, extensible to 5000wan : 10Gb Þ Internet2lan: 40Gb Þ Infinibandplatform: metal + SunGrid

goal: ATO approved regulatory next-gen support platform for long term storage and large scale computations; to support regulatory submissions for NGS and standardization portal for NGS evidence submissions

mini-HIVE

location: White Oak/CBER server roomstorage: ~1 Petabytescpu: ~1500 coreswan: 10Gblan: 56 GBplatform: barebone metal

goal: research and scientific NGS portal with cutting edge production quality tools

Public HIVE as MDEpiNet Resource

Public-elastic HIVE

location: ColonialOne/Ashburn datacenterstorage: extensible to Petabytescpu:+1000 coreswan : 10Gb Þ Internet2lan: 10Gb Þ Infinibandplatform: Lustre open source

goal: to become extensibility platform for public HIVE users for their large scale computational needs for large clinical research projects.

Public-HIVE

location: GWU Dr Mazumder’s labstorage: ~300 Terabytescpu: ~400 coreswan: 1Gblan: 10 GBplatform: metal

goal: support and integrate wider community of researchers into HIVE process, allow access to cutting edge regulatory complaint tools and standards, perform pilot free projects with academic, industry and government entities to promote and ease the access to novel NGS techniques. To incorporate HIVE into education.

HIVE-ZONElocation: virtual cloudstorage: ~extensiblecpu: ~extensiblewan: ~extensiblelan: ~extensible

goal: support large scale sporadic surge usage patterns for extra large clinical computations through openFDA .gov initaitve for FDA and for openHIVE platform for wider scientific research and education community.

Amazon

HIVE is an ecosystem of hardware/software/expertise allowing developers and users to implement variety of infrastructures/ tools/ visual interfaces manipulate large amount of complex data through sophisticated computational pipelines in this “sandbox” like environment.

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Methods

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ExamplesofExpertise• Causalinferencewithhigh-dimensional,complex,observational

data:– Bayesianpropensityscoreusingregularizingpriordistributions– Robust likelihoodapproachesforcomparingmanydevicesviaSuper

Learning– MakingbetteruseofclaimscodesviaBayesianhierarchicalprior

distribution• Meta-analysisofindividualparticipantdataforidentificationof

device-effectheterogeneity andforOPC construction• Devicesurveillancethatincorporateregulatorlossfunctions• HandlingmissingdatainCRNsthatuseadistributedsystem• CommonDataElements(CDE)• Distributedmodels• Andmuchmore!!!

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Infrastructure

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• Approachistofacilitateand/orleveragenationalinvestmentsinregistriesandotherrelevantdatasystems(dualpurposing)tocreate‘NationalMedicalDeviceEvaluationSystemonafairlyimmediatebasis,greatlyminimizingthecostordevelopmentresourcesneeded’– Major‘Qualityandsafety’registriesinitiatedbyprofessionalsocieties,

states,healthcaresystems,NIH/AHRQ,other– CMSclaimsincludingPartA,B,C,D– Commercialclaims– PCORICDRNs– AllpayerStatedatabases– ComprehensiveEHRs

CRNs

Focusistoprovidetimelyinformationondeviceexperiencesfordecisionmakingbypatients,physicians,regulatorsandallotherstakeholders

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Evolving CRN Portfolio National• OrthoCRN(akaICOR- USA• VascularCRN– VISION• CardiacCRN• NeurologyCRN– DAISI• GastrointestinalCRN– Obesity• SPAREDCRN– Prostateablation• RoboticSurgeryCRN• TMD/TMJ• VANGUARD• Women’sHealthTechnologies–

UterineFibroids,PelvicFloorDisorders,SterilizationDevices,

• BreastImplants(NBIRpilotunderway)

• AbdominalHerniaCRN

International• InternationalConsortiumOrthopedics

Registries(ICOR)• InternationalConsortiumVascular

Registries(ICVR)• InternationalConsortiumofCardiac

Registries(ICCR)• InternationalCollaborationofBreast

RegistriesActivities(I-COBRA)

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www.fda.govResearchers

HealthCareProviders

Patients

HospitalsIntegratedDeliverySystems

EHRVendors

Government

ONC

StructuredDataCapture(SDC)

EHRStatesData

Harmonization/Interoperability

DeviceIndustry

Addressecosystemquestionsefficiently

CoordinatedRegistryNetwork(CRNs)aspartofNEST

Registry Registry Registry

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SelectedDataSources• 10-20yearsofclinicalregistriesdata(national/international)• Hospitaldischargedata• Statedata• Medicare/Medicaiddata• AHRQdatasources• Truvendata• RoPR - Searchablecentrallistingofpatientregistries• GeneExpressionOmnibus(GEO/NCBI)• IngenuityPathwayAnalysis(IPA)• ElectronicMedicalRecordsandGenomicsNetworkatthe• NationalHumanGenomeResearchInstitute(eMERGE/NHGRI)

includingMCRI– MarshfieldClinicResearchInstitute)• Andmore!

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Partnerships

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Example1. RAPID/VISION:AScalableFrameworktoEfficientlyConductReal-worldEnabledVascularClinicalTrials

• TwoMDEpiNetprojectsVISION(ledbyCornel)andRAPID(ledbyDuke)werelaunchedtocomplementeachother

• VISION- todevelopNationalVascularImplantsSurveillanceandOutcomesNetworkbylinkingVQIregistrytoclaimsandotherdatasourcesforlongitudinalassessment

• RAPID- todevelopedacoredataelement(CDE)setinformedbymultipleregistries,EHRsystems,andstakeholders.

• LeveragingbotheffortstheSPEEDpilotisnowbeingdesignedtodemonstratehowclinicaltrialssufficienttosupportregulatorydecision-makingcanbeefficientlyimplementedintoexistinghealthcaresystemsforexpandingtheindications

• TheSPEEDtrialthatwillinvolve12600patientsfromtheVQIregistrywith(estimated4200prospectiveand8400retrospectivepatientsdataand2940patientswith1yearfollow-updataavailablefordevelopingObjectivePerformanceCriteria– OPCs

• TheprojectsleveragetheGUDIDDatabasetoenablecomparativeeffectivenessresearchofperipheralvasculartechnologies.

• ItwillinvolvedatarefinementandanalysestodevelopcontemporaryOPCsusingRWE,datasharingwithindustrystakeholdersforpotentiallabelingmodification(e.g.,longerlesions,heavycalcifiedlesions,diabeticpatients).

• Thenewparadigmisthatindustrywillhaveaccesstotheconglomerateofdataplustheirowndata.Thus,ifpre-specifiedstatisticalplanismetforagivensubgroupanalysispopulationasperexamplesabove,alabelingmodificationcouldberequested/granted.

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Example2.GrowthAcrossClinicalAreas

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Example3.InternationalRegistries• 2011MDEpiNet/ICORregistrylaunchedinorthopedics• 2012-2014– internationaleffortsreplicatedincardiacand

vascularspace- ICCRandICVR• 2014– MDEpiNetproposedtoIMDRFtocreateIMDRF

RegistryWG– andproduceessentialprinciplesdocuments• 2015and2017– ThreeIMDRFregistryprinciplesdocuments

produced(theconceptofinternationalCRN(iCRNs)endorsedbyIMDRFalongwiththeproposedmethodologypilots)

• TheMDEpiNet/ICVRisnowworkingwithmanufacturers,regulatorsandprofessionalassociationstochampionthefirstinternationalpilottoforexpandingtheindicationsforrAAAdeviceswhileapplyingtheprinciplesofIMDRFregistrydocuments

• ThegoalistofinalizetheprotocolbyDecember2017

Danica.Marinac-Dabic@fda.hhs.gov