Reducing Barriers to Clinical Trials Data Sharing: Cooperative … · 2017-01-31 · clinical trial together with a summary that is understandable to a layperson, and the clinical

ReducingBarrierstoClinicalTrialsDataSharing:CooperativeSciencetoImprovePublicHealth

Valuingpatientcontributions,respectingexistingresearchcommunities,andincreasingdiscovery

RebeccaLi,PhD,ExecutiveDirector

MRCTCenterMission

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Engagediversestakeholderstodefineemergingissuesinglobalclinicaltrialsandtocreateandimplementethical,actionable,andpracticalsolutions.

ClinicalTrialsDataSharing:Audiences

Thesharingofdatafromclinicaltrialswithotherresearchersorthegeneralpublic,includingindividualparticipantdata(rawdata),metadata,andsummary-leveldata

ClinicalTrialData

StudyParticipants

ResearchersPublic



ClinicalTrialData

StudyParticipants

ResearchersPublic

EuropeanRegulation

EUParliament:Regulation(EU)No536/2014(2014):

Sponsorofaclinicaltrialmustsubmit“asummaryoftheresultsoftheclinicaltrialtogetherwithasummarythatisunderstandabletoalayperson,andtheclinicalstudyreport,whereapplicable,withinthedefinedtimelines.”

Article37:Irrespectiveoftheoutcomeofaclinicaltrial,withinoneyearfromtheendofaclinicaltrialinallMemberStatesconcerned,thesponsorshallsubmittotheEUdatabaseasummaryoftheresultsoftheclinicaltrial.

EURequirespostinglaypersonssummarytoEUPortal– by2017/2018

ReturningResults- MRCTMission

Ø Goals:ReturningClinicalTrialResultstostudyparticipantsØ Developstandardsandbestpractices.

Ø Createaguidancedocument,includingtemplates.

Ø Addressperceivedbarrierstowidespreadimplementation.

Ø Returningresultsallowssponsorsandinvestigatorstorecognizeandhonortheessentialcontributionsandvolunteerismofclinicaltrialparticipants.

Ø Expectationsofacademic,industry,not-for-profitsponsorssimilar

Ø ReturningresultsisakeyaspectofImprovingTransparencyofclinicaltrialsandIncreasingPublicTrust.

ProjectScope:Communicationanddisseminationofsummaryresearchresultstoindividualparticipants

TheMRCTCenterTools&Deliverables

AnRORGuidanceDocumentforgroupswishingtoreturnresultsincluding:• Logisticsanddetailedprocessesforresultssharing• Contentofresearchresultsummaries• Culturalandhealthliteracyconsiderations• Timing

AnRORToolkitincluding:• TemplatesforPhase1,2&3,studiesendingearly• Neutrallanguageguide• Endpointslanguageguide

Goto:mrctcenter.org-- Resources– Returnofaggregateresults

http://mrctcenter.org/news/updated-versions-of-return-of-results-guidance-document-and-toolkit-released/

AlignedwithHRAguidelineswhichreferstothesedocuments

ParticipantClinicalTrialResultsSummaries-Process• Writeinunbiasedandnotpromotionallanguage• Obtainreviewbyindependentandobjectiveeditor(s)andpatient

representative(s)whenpossible• Translateintoadditionallanguagesconsistentwithtranslationsof

informedconsent• Makeavailableanindividualfromthestudysiteorneutralinformed

thirdpartytoanswerquestionsforparticipants• Makeprovisionsforvulnerablepopulationsandotherinstances• Considerastowhethertoinform,andwhomtoinform,intheevent

ofaparticipant’sdeath• Useplainlanguage(sixth-eightgradereadinglevel)• Applyhealthandnumeracyprinciples

Returnofresultstemplates

• Located in MRCT Return of Results Toolkit

• Templates for Phase 1, Phases 2 and 3, and Trials ending early

• Includes examples

• Incorporates principles of Health Literacy and Numeracy

ParticipantClinicalTrialResultsSummaries- Example

Content ExampleWhy thestudywasdone(cont.)

Forclinicaltrialsthatstopearly:Thisstudywasstoppedearlierthanplanned.Thiscanhappenformanyreasons.

Thisstudystoppedearlybecause[addoneofthepossiblestatementsbelow,oryourownsimpleexplanation,tothissentence.Ifthereismorethanonereason,listallthatapply.]…toomanyparticipantshadsideeffects(seebelow).…[druggenericname]didnotimprovepatientresults.…[druggenericname]wasnotaseffectiveasexpected[comparator].…[druggenericname]wasmuchmoreeffectivethanexpected.[ifapplicable,add]Thestudywasstoppedsoallparticipantshadachancetotake[druggenericname].…notenoughpeoplejoinedthestudy.[Includeastatementaboutwhatwillhappennext.…• Forsideeffects..• Forefficacy…• Forfutility…• Lowaccrual:….]1/31/17 10

NeutralLanguageGuideLanguagetoavoid Languagetoconsider

Thisstudyproved… Thisstudyfoundthat...Thisdoesnotmeaneveryoneinthatgrouphadtheseresults.

Thisstudyprovedthatusing<drugA>toprevent<disease/condition>iseffective.

Thisstudyfoundthatpeoplewith<disease/condition>whogot<drugA>had<primaryendpoint>.

Thismeansthat<DrugA>isbetterthan<DrugB>.

Inthisstudy,peoplewhogot<drugA>hadmore<studyendpoint>thansomepeoplewhogot<DrugB>withthesamehealthconditions.

<DrugA>isbettertoleratedthan<DrugB>.

Inthisstudy,fewerpatientswhotook<DrugA>had<listspecificadverseevents>thanpatientswhotook<DrugB>.

SimilarprincipleshavebeensuggestedbyTransCelerate BioPharma:RecommendationsforDraftingNon-PromotionalLaySummariesofClinicalTrialResults

EndpointDescriptionsandExamples

Endpoint Descriptionofthetypeofendpoint Exampleinsimple,plainlanguage

Composite Acompositeendpoint,astheprimaryendpoint,combinesmultipleoutcomes(e.g.death,gettingsickagain(relapse),seriousevent)andtestresultsintoonemeasureofhowwellthedrug/therapy/deviceworks.Thisisusefulwhentherearemanydifferentoutcomesthatcanhappenduringatrial.Thiscanalsobecalledacombinedormulti-partendpoint.

“TheXXXstudymeasured[patients/people]toseeifthoseinGroupA(ABCtreatment)orGroupB(XYZtreatment)livedlonger,hadfewerheartattacks,orfewerhospitalvisitsforheartfailure.Theseeventsweremeasuredtogether(combined)becauseeachoneisquiterare.Researchersalsowantedtoseeifthedrugworkedinpatientswhohadall3conditions.Thestudyfoundthattherewasnochangeinthenumberofeventsfor[patients/people]inGroupAorGroupB.”

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Numeracy:Overview

• Theabilitytousebasicprobabilityandmathematicalconceptstoexplainmathematicalandstatisticalterms.

• Numeracyprinciplesinhealthliteracyfocusonsimpleexplanations,insteadofusingcomplexfractions,percentagesorstatisticalterms.

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NumeracyPrinciples:Implementation

• Lessismore– howcriticalarethenumbers?• Providefewerchoices– choosestrategicallywhichoptionstoshow• Dothemath– calculateorconvertnumbers,readersareunlikely

toconductevenbasicmath• Givenumbersmeaningandcontext– explainwhatnumbersmean• Usecommontermsandimaginableformats• Usevisuals• Usewholenumbers• Useconsistentdenominatorsandtimeframe• Naturalfrequenciesvspercentages– “1outof10”maybemore

usefulthanpercentagesbecauseitgivescontextandimagery

From:“HealthLiteracyMissouriBestPracticesforNumeracy,”citedinMRCTReturnofResultsToolkit.(2016),Appendix4 14

14%Or

About 1 in 7

Example

Example

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In 20% (or 1 in 5) of patients,tumors got at least 30% smaller

In 80% (or 4 in 5) of patients,tumors did not get at least 30% smaller

Returnofresults:MRCTCenterworkgroup

Academic/MedicalCenter:CarmenAldinger– MRCTCenterMarkBarnes- Ropes&Gray,LLP/MRCTCenterBarbaraBierer- Brigham&Women'sHospital/MRCTAssuntaDeRienzo - Brigham&Women'sHospitalAlla Digilova – MRCTCenterRebeccaHLi– MRCTCenterHollyFernandezLynch- HarvardLawSchoolPearlO'Rourke- PartnersHealthCareNesri Padayatchi - Univ.ofKwaZulu-NatalAmishShah- MRCT/HarvardLawSchoolZacharyShapiro– MRCT/HarvardLawSchoolPatrickTaylor- Children'sHospital,BostonSarahWhite- PartnersHealthCareElizabethWitte– HarvardMedicalSchoolSabune Winkler– HarvardMedicalSchoolIndustry/TradeAssociations:SalvatoreAlesci – PhRMARichardBergstroem – EFPIAElizabethGarofalo - NovartisPharmaAGLauraHagan- MerckSeranoSandraHayes-Licitra – Johnson&JohnsonAngelikaJoos – MerckSharp&DohmeBarbaraKress– MerckSarahLarson– BiogenIdecDavidLeventhal– PfizerCraigLipset – PfizerLaurieMyers– Merck(CO-CHAIR)

AlexNasr– AbbVieMaryAnnPlummer– J&J(priorCO-CHAIR)SandyPrucka – LillyBenRotz – LillyBethRoxland– Johnson&JohnsonJessicaScott– GSKInstitutionalReview Boards:DavidForster- WIRBCopernicusGroupMaryOster– NEIRBJimSaunders- NEIRBNonprofit:Behtash Bahador – CISCRPPhyllisFrosst - PersonalizedMedicineCoalitionZachHallinan– CISCRPMarcWilenzick– InternationalAIDSVaccineInitiativePatientAdvocates:NicolaBedlington– EuropeanPatientsForumDeborahCollyar– PAIR(COCHAIR)DavidHaerry – EuropeanAIDSTreatmentGroupCherylJernigan- SusanG.KomenYannLeCam – EURODISMarcelloLosso - HIVRAMOSJanePerlmutter – GeminiGroupResearch/ConsultingFirms:BarbaraGodlew - TheFAIRECompany,LLCPierreGervais- QTResearchPauloLacativa - CCBRClinicalResearchDavidWalling– CollaborativeNeuroScience

QuestionsonPlainLanguageSummaries?

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ClinicalTrialData

StudyParticipants

ResearchersPublic

OurWorkinDataSharing

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••Harmonizinglanguage&agreementsamongsponsorsPolicy

••Loweringbarrierstodatasharing••AcademiccreditfordatasharingAdvocacy

••Creatingaplatformfordatasharing••Makingdataonotherplatformsmorediscoverable

Implementation

Policy

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••Harmonizinglanguage&agreementsamongsponsors

Policy

• DataContributoragreement

• DataUseagreement

• Informedconsentagreementlanguage• IRPPrinciplesdocumentdefinedforparticipatingIRPs

Policy

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••LoweringbarrierstodatasharingAdvocacy

• Conveningstakeholderswhoarecurrentlysharingandthosewhodonotcurrentlyshare

• Lowerthebarriersforthosewhodonothavetheresourcesorknowledgetosharedata

• Advancepolicychangesthatenableacademiccreditfordatathatismadewidelyavailablefortheadvancementofscienceandmedicine

Policy

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Createasustainableglobaldata-sharingplatform

Implementation

• LaunchVivli,anon-profitcenterforglobaldatasharing

• Makingdataonotherplatformsmorediscoverablethrougharobustsearchengine

MajorClinicalTrialDataSharing:Platforms

• CSDRPLATFORM- leadingindustrymulti-sponsorrequestsite

• Clinicaltrials.gov – searchabledatabaseincludingsummaryresults

• J&J- YODA project- YalepartnerswithJ&J/Medtronic

• Duke ClinicalResearchInstitute– BristolMyersSquibbStrategicInitiative(SOAR),whichsupportsopenaccesstoclinicaltrialsdata

• ProjectDatasphere – cancercomparatordata,andmore

• NIHdatarepositoriesand(BIOLINCCand60+others)

• FDA Oncology’sdataaggregationeffort- InformationExchangeandDataTransformation(INFORMED).

• OPENTRIALS – indexesallfreelyavailableinformation,noIPD

• EMADatabase– CSRssubmittedtotheagencyaspartofaMAA

CurrentPlatformDifferentiatingFactors

FACTOR VARIABLES

Data types Summary leveldata IPDdata*

Reviewprocess No review Discretionary Review

DataStandards Specificformatrequired Multipleformatsaccepted

Contributor Members only Anyresearcher

Requestor Researcher/Expert Public/no qualifications

Hosts data No Yes

Downloadabledata No Yes

Review ofrequest None Discretionary

Analysis space Noneprovided Spaceandlicensed toolsprovided

Specificityofplatform Specificto sponsortype,geographyortherapeuticarea

Multi-stakeholder, global,alltherapeuticareas

Connect/search otherplatforms

No Yes

1/31/17 25*IPD– IndividualParticipantleveldata

CurrentPlatformDifferentiatingFactors

FACTOR VARIABLES Vivli

Data types Summary leveldata IPDdata*

Reviewprocess No review Discretionary Review

DataStandards Specificformatrequired Multipleformatsaccepted

Contributor Members only Anyresearcher

Requestor Researcher/Expert Public/no qualifications

Hostsdata No Yes

Downloadabledata No Yes

Review ofrequest None Discretionary

Analysis space Noneprovided Spaceandlicensed toolsprovided

Specificityofplatform Specificto sponsortype,geographyortherapeuticarea

Multi-stakeholder, global,alltherapeuticareas

Connect/search otherplatforms

No Yes

1/31/17 26*IPD– IndividualParticipantleveldata

CurrentGap

Weandothershaveidentifiedsignificantcurrentchallengestoutilizingexistingdataonclinicaltrialsforfurtherresearch:• Manyacademiciansandothersdonothaveameanstomakedata

availableinaturn-keyfashion.• Althoughtechnologyhasmadeiteasiertomakedataavailable,

dataarestilldifficulttodiscover.• Arobustcentralizedsearchenginedoesnotexisttolocatedata

acrossthedifferentdatageneratorsanddataplatforms.• Combingdatasetsfromdifferentgeneratorsisresource- andtime-

intensiveduetoinconsistentadoptionofdatastandards,datarequirements,securitystandardsandpolicies.

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WhyVivliisNeeded

• Datahostingcapacity– VIVLIisageneralaccessdataplatformthatflexiblydesignedtomeetglobal

capacityneeds

• Analyticfunctionality/value– currentfederatedarchitectures(e.g.,SENTINEL,PCORnet)offeronly

limitedanalyticcapabilities(e.g.,counts)– Toenablemeta-analysisandotheraggregatedanalyses,datasetsneedto

beheldinasinglehostenvironment– ThegreatertheproportionofIPDdatasetsheldbyonehost,thegreater

theabilitytodoaggregatedanalyses– NootherplatformaimsforVivli’sscaleandscopeofIPDhosting

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CenterandBackground

TheMulti-RegionalClinicalTrialsCenterofBrighamandWomen’sHospitalandHarvardUniversity(MRCTCenter)haschampionedeffortstoenhancesharingof,

andaccessto,clinicaltrialsdataaroundtheworld.

Vivliisbeingformedtoprovidegovernanceandmanagementofaplatform—agnostictodisease,country,sponsorandfunder—toreducebarrierstoclinical

trialsdatasharing.

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Variousstakeholderpositions

• Industry– Datasharingon“multi-sponsor”orsingleinstitutionplatforms– Attheleadingedgeofdatasharing– Allrequirereviewfordata

• Academic– Noinstitutionalsolution;creatingURLsorusingother(e.g.NIH)resources– Individuals:(1)Ifshare,prefertodelegatemanagementwithopenaccess

or(2)closelyheldunderstrictcontrolsforaccess

• Non-profitandpatientadvocacygroups– Generallyencouragingofdatasharingwithappropriateparticipant

informationandconsent– Appreciatethat“standaloneplatforms”losethevalueofinteroperability

andofcollectiveadvantageof“bigdata”

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1) Enablinginteroperabilityofdatafrommultiplesources;

2) Hostingdataforstakeholdersthatdonothavetheabilitytodoso;

3) Coordinatingandpartneringwithexistingdata-sharinginitiatives,policies,andprocessesasappropriate;

4) Promotingreasonedsolutionstochallengesofdatasharing.

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Scope

Mission

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Promote,coordinate,andfacilitateclinicalresearchdatasharingthroughthecreationandimplementationofa

sustainableglobaldata-sharingenterprise

TheUniqueRemitofVivli– EnhancingDiscovery

Advancedmetadatasearchanddiscovery capability

Simplified access request systemtodataresidingonotherplatforms

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Searching multipledatabasesina

fragmentedlandscape

Discovery ofdatacanbechallenging

Morecommunitiesandpartners=morediscoverabledata

Astheenhancedmetadatacatalogmatures,moredata,includingexternallyhosteddata,willbediscoverablethroughVivli

TheUniqueRemitofVivli– ProvidingVisibilityandCombiningDatainaCentralizedPlatform

CombinedIndustry,Academic,andBiotechdatadiscoverablethroughonesearchengine

Anonymized IndividualParticipant-LevelData(IPD)availableforrequest

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VivliSolutionsOfferings

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VivliSearchandRequestTool

VivliYodaCSDR

GSK Lilly Takeda RocheEtc. JnJ Medtronic Vivli

More

Other

IRP IRP IRP IRP

OpenSearch UserRequest ApprovedRequest

Secureanalytic

Environment

Dr.XData

Vivli

Yoda

GSK

Centralizedsearchandrequestportalfordatahostedonmultipleplatforms

EnhancedMetadataformoreprecisesearchresults

SecurespacetocombineIPDdatafrom

multiplesources,includinguploadofacademicdata

Hostingforclinicaltrialdata,includingmintingDOI forpublicationpurposes

Respectingothercontributorreview

processesanddatausetermswhileprovidinguserwithcentralizedmechanismforrequest

Examplesofexistingplatforms

ExampleofNewSearchFunctionality

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DevelopmentAdvisorsandSupporters

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TheMRCTCenterwouldliketothankthefollowingsupportersandfunders*fortheircontributionstotheVivliproject:

• DeloitteConsulting• GlaxoSmithKline• TheInstituteofMedicine• TheLauraandJohnArnoldFoundation• Johnson&Johnson• TheLyda HillFoundation• PfizerFoundation• WellcomeTrust

*Inalphabeticalorder

ChallengeswithLaunchingaNewPlatform

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• CreateincentivestructureswithinVivli forsharingwithexternalmandatestorequireclinicaltrialdatasharing

• Harmonizingrequirementsofdiversestakeholders• AcceleratingtheVivlitimelinetolaunch• Maintainlowfinancialbarrierstoentry

Joinus

• Partnerwithus- ourmissiontoistoaccelerateyourdiscoveriesthroughintegratingofdataglobally acrossplatformsanddatabases

• Pleasecollaboratewithusbymakingyourdatadiscoverable

• ConsiderlearningmoreaboutsupportingtheVivli effort

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THANKYOU

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Reducing Barriers to Clinical Trials Data Sharing: Cooperative … · 2017-01-31 · clinical trial together with a summary that is understandable to a layperson, and the clinical

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