Cardiovascular Device-Coordinated Research Network (CDCRN)
Pablo Morales, MDOn behalf of John Laschinger, MD
FDA Division of Cardiovascular DevicesMDEpiNet Annual Meeting
October 20, 2017
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Goal• To create a re-usable infrastructure designed to
efficiently and effectively conduct randomized controlled trials (RCTs) and non-randomized clinical studies necessary to provide the evidence needed for clinical and regulatory decision-making, comparative effectiveness research, and timely issuance of Societal treatment guidelines supported by data.
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Background• Outside of the US, the Internet-based Swedish Web
System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry has proven the benefits of registry use for creating a re-usable infrastructure for the conduct of large simple randomized clinical trials (RCT’s).
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NEngl JMed2013;369:1587-97.
Registry-embedded RCT’sProspective Evidence Acquisition –”Precision + Accuracy”
*
LaschingerJC
DOI:10.1056/NEJMoa1706222 DOI:10.1056/NEJMoa1706443
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SWEDEHEART RRCT Methods (iFR vs. FFR)RegistryEmbedded- TheSwedishCoronaryAngiographyAndAngioplastyRegistry(SCAAR)
• Demographics,baselineclinicaldata• Eligibility– minimalentrycriteria• Randomizationandassignment
ModularAdd-onData(On-lineQuestionnaire)• Specifictrialrelatedangiographicandphysiologicassessments• Proceduraldata,protocoldeviations
Linkages - PrimaryandKeySecondaryOutcomes(within12months;100%f/u)• Primary
§ Death§ MIandUnplannedRevascularization
• KeySecondaryEndpoints:§ TargetLesionRevascularization§ Stentthrombosis§ TargetVesselRevascularization
Adjudication – Keyoutcomeevents(blinded)• DeathandMI(CEC)• UnplannedRevascularizationandsecondaryangiographicoutcomes(independentobserver)
• NationalPopulationRegistries• SWEDEHEARTandSCAARRegistries• DanishNationalPatientRegistryandWesternDenmarkHeartRegistry• ResearchNurse(Iceland)
LaschingerJC NEJM376;1813-1823
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US SWEDEHEART equivalent is CDCRN
• FDA would like to facilitate the creation of a similar infrastructure within the US, – Designed to be sustainable, robust and re-usable– Capable of providing a registry based platform for
the Pre-Market evaluation of cardiovascular medical devices.
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ConceptIncludes key design features: • Interoperability – Shared definitional and temporal
framework across data sources• Connectivity – ability to leverage data from other
sources • Flexibility – baseline dataset and ability to accept
modular add-ons, auto-population by EHR • Sustainability - Ability to fulfill the evidentiary needs
of multiple regulatory and non-regulatory users
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FDA
ClinicalCommunity
&Public
Goal:provideuniquelyreliableclinicalandregulatoryevidenceabouttheaverageeffectsofthewidespreaduseofstudiedtreatmentsonimportantoutcomes(e.g.
mortality)
CDCRN embedded Large Simple RCTPre to post Market Evaluation – TELC
EVIDENCE
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Available Registries and Datasets in the US CV Procedures, Devices and Outcomes
STSNationalDatabases
ACCNCDRegistries
Gov’tDatasets
STS/ACCTVTRegistries
LaschingerJC
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§ NCDRCath/PCI(Adult)*§ >98%ofallprocedures§ >1,600hospitals
§ ImplantableCardioverterDefibrillator(ICD*)§ 100%§ 1,715Hospitals
§ LeftAtrialAppendageOccluder(LAAO)§ 100%
Registry PenetranceClinical Data Acquisition of Hard Endpoints
*JAmCollCardiol:http://dx.doi.org/10.1016/j.jacc.2016.12.004 +AnnThorac Surg 2016;102:1790–7#AnnThorac Surg2017;103:1021–35
LaschingerJC
§ STS+ NationalDatabases§ AdultandPediatric§ SiteandPatientlevelpenetration-
>95%§ 1,117AdultCenters,§ 121CongenitalCenters§ AcquiredINTERMACS,PediMACS
§ TVTAorticandMitral#§ 100%§ >523Sites
§ IMPACT(Pediatric)*§ >90%§ 76Hospitals
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Available STS/ACC Procedure Based RegistriesCapabilities, Strengths, & Needs
EXISTINGCapabilitiesandStrengths
“Early” Data Quality• Accuracyandcompletenessofprocedural
anddischargedata• Abstraction– checkonEHRAccuracy
Sustainability• Riskprediction,benchmarking• Abilitytofulfilltheevidentiaryneedsof
multipleregulatoryandnon-regulatoryusers
• QA/PI
Interoperability• Coredatasets• Commondefinitionalframework
Connectivity• Abilitytolinkwithadministrative
databasesestablished
NEEDEDCapabilities
“Late” Data Quality• Longitudinallossofpatientfollow-up>
30days• Minimizemissingdata
Enhanced Connectivity• Facilitationofdirectlinkagesamong
multipleinteroperabledatasourcesovertime
• Repetitiveprocedurebasedhardoutcomes
Flexibility• Elasticity- Abilitytoacceptmodular
add-ons,scalebasedatasettostudyrequirements
• Improvedacquisition- Embeddingofresearchdatacollectionintoroutineclinicalworkflowandparticipatingpatients’dailyactivities(e.g.EHRautopopulation)LaschingerJC
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CDCRNCentralDatabase
(Trial,demographicandDeviceData)
BroadConsentatStudyenrollmentforuseofIPI* tocreateaCDCRNcentraldatabaseto:• Identifyandtrack all
Patientsenrolledin specificstudiesover“x”years• Flagging NewRecordsin
anyAcademicSocietyDatabase
• Harvesting RecordsFromGovernmentalDatabases(e.g.indexprocedureanniversary)
STSNationalDatabases
ACCNCDRegistries
STS/ACCTVTRegistries
Gov’tDatasets
Continuetooperateindependentlytofulfilltheircurrentindividuallydesignedessentialandsustainablemissions
DirectlylinkalreadyexistingProfessionalSocietyRegistries
&GovernmentDatasets
Createareusableinfrastructureforclinicalandregulatory
evidencegeneration
LinkedRegistriesandDatasets
*IdentifiablePersonalInformation
CDCRN ComponentsEmbedding Clinical Trials in Existing CV Device Registries
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CDCRN Overview
LaschingerJC
CMSSSA-DMFCDC-NDI
AllproceduralrecordsgeneratedinanyCDCRNregistryfor“x”
years
STS-ACCTrial,Device&
DemographicDatabase(TDDD)
LinkedToCDCRN
IndexProcedureDataExtractedTrial,Device,andIdentifiablePersonalInformation(name,SSN,DOB,etc.)
Automaticqueryonindexprocedureanniversarydate(Yearlyfor“x”years)
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CDCRN Overview Data to Sponsor
CDCRNCentralDatabase
Programming:1. DocumentBroadConsentforDirect
Matching2. Allow• FlaggingorHarvesting ofallpatientrecordsgeneratedinCDCRNRegistriesovertimeusingdirectmatching(Name,DOB,SSN,Gender)• SequestrationwithSponsor
• IndexProcedureandmodularadd-ondata• flagged/harvestedrecords
ClinicalTrialDatasourcesforIndex
Procedure
• Hardoutcomes– survival,deviceperformanceandprogressionofCVdiseaseovertotalproductlifecycle
• PASandSurveillanceNeeds
ModularAdd-onDatasets
(Procedural,QoL,imaging,etc.)
IndexProcedureData:
(SponsorCRF,AppropriateRegistryDCF)
SequentialProcedurebasedoutcomesandadministrativedataforfollow-upofdeviceperformance&patientoutcomesoverindefiniteperiodsoftimewithouttheneedfordirectpatientcontact.
LaschingerJC
(Trial,demographicandDeviceData)
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CDCRN has the potential to fulfill criteria identified by the Medical Device Registry Task
Force The 5 priority principles for forming a Coordinated Research Network:1. The ability to uniquely identify medical devices (UDI could be
added as a data field to existing registries and datasets – not essential with name and SSN for linkages);
2. Implementation of standardized clinical vocabularies and dictionaries;
3. Reusable interoperability solutions linking diverse, strategically complementary data sources;
4. Partnered, inclusive governance; and 5. Value-based, incentivized sustainability.
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At FDA White Oak campus on Wednesday, November 29, 2017 from 8AM to 4:30PM by:• John Laschinger, MD, Division of Cardiovascular
Devices Medical Officer and CDCRN Lead• Bram Zuckerman, MD, Division of Cardiovascular
Devices, Director• Nicole Ibrahim, PhD, Division of Cardiovascular
Devices, Deputy Director (Acting)With participation of all stakeholders identified during this presentation.
CDCRN to be launched
Thank You
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