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