GlobalDataSharingandTransparencyIni7a7ves

BarbaraE.Bierer,MDbbierer@partners.orgMAGIConference May3,2016

F494:TheNewWorldofTransparencyforClinicalTrialResults

Disclaimer:

•  Theopinionscontainedhereinarethoseoftheauthorsandarenotintendedtorepresenttheposi7onofBrighamandWomen'sHospitalorHarvardUniversity.

•  TheMRCTCenterissupportedbyvoluntarycontribu7onsfromfounda7ons,corpora7ons,interna7onalorganiza7ons,academicins7tu7onsandgovernmenten77es(seewww.MRCTCenter.org)andwellasbygrants.

•  WearecommiOedtoautonomyinourresearchandtotransparencyinourrela7onships.TheMRCTCenter—anditsdirectors—retainresponsibilityandfinalcontrolofthecontentofanyproducts,resultsanddeliverables.

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Engagediversestakeholderstodefineemergingissuesinglobalclinicaltrialsandtocreateandimplementethical,ac7onable,andprac7calsolu7ons.

OurMission

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MRCTCurrentProjectStatus

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TrainingandCompetencyProtocolEthicsReturnofAggregateResultsTrainingandCompetenciesGlobalRegulatoryEngagementEngagemeDataSharingandTransparencyPost-TrialResponsibili7es

IndividualReturnofResults

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Purpose-drivendatasharingwillenhancescien7ficdiscoveryandpublictrust

•  Benefitsaresubstan7al(e.g.):–  Eliminateduplica7vetrials–  EvaluatecommonAEsbycompoundclassorsubpopula7on–  Iden7fysurrogateendpoints–  Enhancecorrela7veandexplanatoryscience

•  Butbenefitsonlyrealizedif:–  Risksareminimized,withaOen7ontopar7cipantprivacy

•  AOen7ontoinformedconsentandrespectforconsent•  Dataanonymiza7on

–  Dataareinteroperable,datasetscanbepooled•  Datastandardsareavailable,oralterna7vemethodology•  Metadataisshared•  Real-7meanaly7csareavailable

–  State-of-the-artsecurityisinplace

2012-2015MajorMilestonesinClinicalTrialDataSharing:Plaaorms

•  GSKandtheClinicalStudyDataRequest(CSDR)plaaorm,amul7-sponsorrequestsitewheredataareusedinasecureenvironment

•  J&J-YODAprojectthroughwhichYalepartnerswithJ&JandMedtronic

•  Pfizer’sIntegratedSystemforPfizerPIIni7atedResearch(INSPIIRE)Portal

•  DukeClinicalResearchIns7tute–BristolMyersSquibbStrategicIni7a7ve(SOAR),whichsupportsopenaccesstoclinicaltrialsdata

•  NIHBioLINCCdatarepositoryandothers

•  FDA-ProjectDataSphere(cancercompara7vedata)andHigh-PerformanceIntegratedVirtualEnvironment(HIVE),aprivate,cloud-basedenvironmentthatcomprisesdatastoragelibrary,algorithmsforanalysis,andcomputa7onalcapacity

HoweverthesearenotinteroperablenorarethesesystemsintegratedFewvoluntaryacademicorbiotechdatageneratorparWcipants

AccesstodocumentsRequestsforinforma7on

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•  Policy published November 2010

•  ‘Outputs’ table to guide

implementation

•  Change in access policy had big

impact on Agency operations

•  Average 450-500 requests for

information each month

•  But information only goes to the requester and

although they may share, it is less visible

Clinical trial transparency

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EUClinicalTrialsRegister

ProacWvepublicaWonofclinicalstudyreports–Policy70

ClinicalTrialRegulaWonandEUPortalandDatabase–publicinformaWonclinicaltrialsauthorizedinEU

ICJMEdatasharingproposal,26Jan2016

•  TheICMJEdefinesaclinicaltrialasanyresearchprojectthatprospec7velyassignspeopleoragroupofpeopletoaninterven7on,withorwithoutconcurrentcomparisonorcontrolgroups,tostudythecause-and-effectrela7onshipbetweenahealth-relatedinterven7onandahealthoutcome.

•  “Asacondi7onofconsidera7onforpublica7onofaclinicaltrialreportinourmemberjournals,theICMJEproposestorequireauthorstosharewithothersthedeiden8fiedindividual-pa8entdata(IPD)underlyingtheresultspresentedinthear8cle(includingtables,figures,andappendicesorsupplementarymaterial)nolaterthan6monthsaEerpublica8on.Thedataunder-lyingtheresultsaredefinedastheIPDrequiredtore-producethear7cle'sfindings,includingnecessarymetadata.Thisrequirementwillgointoeffectforclinicaltrialsthatbegintoenrollpar7cipantsbeginning1yearakertheICMJEadoptsitsdata-sharingrequirements.”*

•  Anyonecanprovidefeed-backatwww.icmje.orgby18April2016.

hOp://www.icmje.org/news-and-editorials/M15-2928-PAP.pdf

MRCTCenter’sRoleasaNeutralConvener

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Nonprofits

Industry

Pa7entsand

Pa7entOrg

Academia

Gov’t

Journaleditors

Tocreateimplementablesolu1onsfordatasharing

ThePhasesofOurWorkinDataSharing

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DataSharing:CommonICFandDUA

TEMPLATE ICF LANGUAGE FOR DATA SHARING* DATA USE AGREEMENT TEMPLATE

*Panelat2:30todaywilldiscussissuesininformedconsent

DataSharingConference:ConsensusofFutureVisionMarch30-31,2015

•  70representa7vesofpharma,biotech,pa7ent/pa7entadvocates,founda7ons,academics,journaleditorsandothers:

•  Consensusonfuturestrategicvision:1.  Expecta7onsandprac7cesofregistra7onandresultsrepor7ngofall

clinicaltrialswouldberegularizedamongindustryandacademia;

2.  Greateraccesstopar7cipant-levelclinicaltrialdatacouldbefacilitated;

3.  Researcherswouldbeabletoaccessandcombinedataacrossvariousplaaormsandsponsors,tomul7plyopportuni7esfordataanalysis;and

4.  Researchpar7cipantprivacymustbesafeguarded,throughITdesignaswellascondi7onsimposedondatausers.

6/6/16 13SponsoredbytheMRCTCenter,LauraandJohn

ArnoldFounda8onandWellcomeTrust

March2015DataSharingConference:FutureVision

•  OrganizaWonalstructureandGovernance-Acoordina7ng,centralized,interna7onal,not-for-profitorganiza7onwithaccountability;

•  Acentralizedandsingleportal-Acentraluserinterfacewitharobustsearchenginefunc7onality,includinginforma7onontrialsaroundtheworld;

•  Datarequirements–Datastandards,defini7on,dataontologyandmetadatatoallowforandenabletheintegra7onofdifferingdatasetsforanalysis;

•  Sharedorcommonservices–Efficientsharedorcommonservicesacrossdatagenerators/sponsors(e.g.policysesng,datade-iden7fica7on,criteriaforindependentreviewpaneldecisionsorreliance,andsta7s7calservices);and

•  Flexibility–Dataplaaormaccommoda7ngdifferingexpecta7onsandneeds:abilitytohostdata,accessdatafromthirdpartyhosts,ordownloaddataiffreelyavailable.Abilitytou7lizemiddlewaretocommunicatewithanalysisapplica7ons.Analy7cflexibilitynecessary.

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ClinicalTrialDataSharingandTransparencyProject

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ClinicalTrialData

StudyParWcipants

ResearchersPublic

The MRCT Center, the Wellcome Trust, and Arnold Foundation and collaborators have spearheaded a major initiative related to sharing of clinical trials data, to enable stakeholders to comply with ICMJE proposed requirements, pending EU regulations, and IOM guidelines inter alia on clinical trial data sharing. Our goal is to ensure a collaborative, unified approach to a common platform and portal. We convened stakeholders from the US and Europe and beyond on March 21-22, 2016 at the Wellcome Trust to vet the vision of a global, federated portal of all data sharing sites from industry, academia and others with the capacity to host data and render such data interoperable.

•  InStrategy:Wehavelaunched3integratedworkinggroupstodeveloporganiza7onalblueprintforthesuggestednot-for-profiten7ty:

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MRCTGovernance

WorkingGroup

Informa7onTechnology(IT)WorkingGroup

BusinessModels

WorkingGroup

Definepurpose,plan,governanceandscopeofnewen7ty

Developglobal-levelITplaaormblueprint

Developsustainablebusinessmodel

DataSharing:StrategyPhase

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TheMRCTCenter’sDataSharingWorkgroupMembers

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GovernanceWorkStream ITWorkStream BusinessModelsWorkStream

Co-Chairs:MRCTCenterWellcomeTrustArnoldFoundaWon

Co-Chairs:IdaSim(UCSF)BarbaraBierer(MRCT)

Co-Chairs:WellcomeTrustMRCTCenter

TeamMembers:MarkBarnes(MRCTCenter)BarbaraBierer(MRCTCenter)StuartBuck(ArnoldFoundaWon)MarlaJoBrickman(Pfizer)NinaHill(Pfizer)RebeccaLi(MRCTCenter)NickLingler(DeloiceConsulWng)Jus7nMcCarthy(Pfizer)HeatherMarino(MRCTCenter)SandraMorris(Johnson&Johnson)JenniferO’Callaghan(WellcomeTrust)NicolaPerrin(WellcomeTrust)PaulSeligman(Amgen)IdaSim(UCSF)JessicaScoO(GlaxoSmithKlein)CatrinTudurSmith(UniversityofLiverpool)NatalieZaidman(Pfizer)

TeamMembers:GeorgeAlter(UofMichigan)MuntherBaara(Pfizer)BarbaraBierer(MRCTCenter)KrisBolt(MRCTCenter)BrianBot(SageBionetworks)AnneClaiborne(IOM)KhaledElEmam(UofOcawa)GhassanKaram(WHO)MichaelKhan(UofColorado)SeanKhozin(FDA)RebeccaKush(CDISC)RebeccaLi(MRCTCenter)GeneLichtman(HCRI)MichelleMancher(IOM)HeatherMarino(MRCTCenter)ChrisMavergames(Cochrane)EricPerakslis(Takeda)FrankRockhold(GSK)

TeamMembers:BarbaraBierer(MRCTCenter)PatrickCullinan(Takeda)RebeccaLi(MRCTCenter)PeterLyons(Deloice)HeatherMarino(MRCTCenter)NicolaPerrin(WellcomeTrust)RohinRajan(Deloice)

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Vision

Toadvancehumanhealththroughclinicaltrialsdatasharing,therebyrespec7ngandhonoringthecontribu7onsofsponsors,funders,inves7gatorsand,mostessen7ally,clinicaltrialpar7cipants

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MissionPromote,coordinate,andfacilitateclinicalresearchdatasharingthroughthecreaWonandimplementaWonofasustainableglobaldata-sharingenterprisethatwill:

•  Protectstudypar7cipants’privacyandrespectthelegi7mateinterestsofdatagenerators,fundersandsponsors

•  Encompassthefullbreadthofclinicaltrialsfundedandconductedbyacademia,government,industryandothers

•  Respectandbridgetoorincorporateexis7ngdatasharingplaaorms

•  Providethecapabilitytohostandanalyzedata,aswellastoenablediscoveryofdataonexternalorgeneratorplaaorms.

•  Interactwithandcomplementcurrentregistries,resultsrepor7ngplaaorms,andregulatoryini7a7ves

•  Provideanindependentreviewprocessfordatarequests,whererequired

•  Developglobal,fairdatasharingpoliciesandprac7ces6/6/16 19

Scope

Thisdatasharingini7a7vewillfunc7onasaplaaormforthesharingofclinicaltrialsdatabyhos7ngdataforstakeholdersthatmaylackthenecessaryresourcestodosoandbycoordina7ngandintegra7ngexis7ngini7a7ves,asappropriate.Phasedapproach:•  PhaseIlaunch,withdefini7onofminimumviableproduct(MVP)•  PhaseIIandbeyond:acquisi7onanddevelopmentofaddi7onal

func7onali7es

FocusonIPD

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•  Vivli,adaptedfromtheGreekwordforlibrary,‘vivliothiki,”andtheLa7nroot“viv,”orlife.

•  WehopeVivli“thelibraryoflife,”willevokecoopera7on,collabora7onandadetermina7ontorespectthealtruismofclinicaltrialpar7cipantsworldwideforthebenefitofmedicineandpublichealth.

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Thedatasharingorganiza7on:iden7tyandbrand

Vivlitoestablishresourcesandexper7setopromotetransparency,standardsandequity

•  Abilitytohostdataandaggregatedata

•  Dynamicanaly7ctools

•  Commontemplatesandresources:–  Publiceduca7onandtools–  Informedconsenttemplates,op7mizedforcountryandpurpose

–  Datacontributoragreements

–  Enforceabledatarequesteranddatauseagreements,specificforpurpose,thatprohibitre-iden7fica7oninteralia

•  Independentreviewpanels(orrelianceagreements)fordatathataresubjecttointermediaryreview

•  Datastandardsanddatacura7on

•  Risk-baseddataanonymiza7on

•  Developmentofstandardsandframeworkstointegratedataplaaorms

•  State-of-the-artsecurityprovisionstominimizerisk6/6/16 22

ProposedOrganiza7onalStructureforNonProfitVivli

BoardofDirectors

Finance&AuditCommiOees

AdvisoryTechnicalCommiOee

ExternalAdvisoryCommiOee

President/ExecDirector

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ApproachtotheWork

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UseCaseDocuments–Definescope,u7lityandfeaturesetofITplaaormincluding:

•  DataAnalysisUseCases•  Outlinehowdatauserswillinteract

withtheplaaormtofind,request,andanalyzedata

•  Analyzingpublishedandunpublisheddatafromstudies

•  DataSubmissionUseCases•  Outlineshowdatageneratorswill

depositdataintheplaaorm•  Addressesanonymiza7onanddata

standardiza7onissues

MRCTCenterITWorkgroup

PlaeormUseCases

DataSharingPlaaorm

5Essen7alDomainsforPlaaorm

PlaeormTopics

IPDIntakeandCuraWon Mustbeabletointakeandcuratedatawithflexibilitytoscaletonewtypesofdata

CatalogMetadataandDatasetIdenWfiers

Musthaveaccuratestructuredmetadataanduniqueiden7fiersforeachdataset,toenableprecisegranularsearching

ReviewProcessforRequests Mustbeabletoaccommodatedifferentreviewrequirementsandprocesses

AnonymizaWonandDUAs Cri7caltomaintainpar7cipantprivacy

AnalysisToolsandWorkspace Musthaveasecureanalysisspace,enablingasmuchcross-datasetaggregra7onaspossible,withtheflexibilitytodevelopaccommoda7onofmanytypesoftools

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Overviewofplaaormdatasharingscenarios

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VivliPlaeorm

CatalogMetadata

Non-IPDe.g.,protocol,SAP,

IndividualPaWentData(IPD)

Analy7cEnvironmentandTools

SAS R etc.

Query,Request,andAnaly7csUserInterface

IPD

IPD Non-IPD

R

ScenarioA

ScenarioB

Non-IPD

SAS

PossibilitytoaggregatedatasetsacrossSAS

environments

DataRequester

Userauthen7ca7onDatauseagreement

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250trials

Sponsorno8fiesplaOormof#of

par8cipa8ngtrials

Plaaormcurates

metadataforthe250trials

IPDSHARED

SearchabletermsmatchavailableIPD

Reviewprocess

PlaaormPar7cipa7ngTrials(e.gSponsors)

•  NoIRPreview•  Plaaormreview•  Datageneratorreview

PlaaormPar7cipa7ngTrials(e.g.Publica7on-based)

• Publica7onpreparedforsubmission

SubmissiontoJournal

• DataPackagePreparedforPlaaorm(anonymized)

SubmissiontoPlaaorm

•  IPD/DataPackageandPublica7onheldinEmbargo

Ar7clePublished&Dataavailableonplaaorm

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WhyVivliisNeeded

•  Datahos7ngcapacity•  Analy7cfunc7onality/value•  Economiesofscale

–  Technical–  Policy–  Opera7onal

•  Lowercostssecondarytoeconomiesofscale

Ø Buildingupon,leveraging,andpartneringwithexis7ngplaaormsandcrea7nganewonlythatwhichisessen7al

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Connec8ngcurrentclinicaltrialplaOormsHos8ngtrialsthatdonotcurrentlyhaveahomeOfferingaddi8onalservices-  Advancedsearchcapabili8es-  Anonymiza8on-  Sta8s8calanalysistools

- 

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Anewglobalplaeormfordatasharing

Comments,ques7onsanddiscussion