standards and ontology-driven workflow automation of ... sde/zabrowski.pdf · standards and...
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©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork1PointCrossLifeSciences
StandardsandOntology-drivenWorkflowAutomationofClinicalStudies
www.pointcross.com
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork2PointCrossLifeSciences
• Multiplelaboratories,investigationsitesandcontractresearchorganizationsareinvolved--- Workflowsareinter-organizational
• Expensiveandverytimeconsumingdatamanagement,programmingandstatisticalanalysiseffort--- 75%to80%oftimeisspentwithwranglingwithdatatogetittothepointwherestatisticalanalysiscanbeperformed*1*2
• Regulatedanddesignedforsubmissiontoregulatoryagencies--- GCP,GLP
• RecentmandatesrequirethatthecollecteddatabeorganizedunderCDISCexchangestandardsandanalysisdatasetsbesubmittedinADaM --- Digitaldatainstandardformatsareheretostay.
• NewStudyProtocolsandProtocolAmendmentsareexpensiveandaddsignificanttimetothelifecycleofstudies--- cantheirproductionbestreamlined.
CharacteristicsoftheClinicalTrialWorkflow
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork3PointCrossLifeSciences
ClinicalStudyWorkflow(Lifecycle)– “AsItHasBeen”
DataAnalysis Plan(SAP)
DataCollection DesignCase Report Form (CRF)
DataCollection by Sites
ClinicalDevelopmentPlanStudyDesign
Protocol
ClinicalStudyReportSubmission Planning
&Packaging
CROs,Programers,Bio-Statisticians
ClinicalDevelopmentPlan
DataAnalysis,CohortAnalysis,TFLs
CTMS
CDMS
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork4PointCrossLifeSciences
ChainingblocksofInter-OrganizationalWorkflows
Organization- CRO
ODMof“CRO”
• Workflows
• Analysis
• Search
ExchangeFormat
• StandardsManagement
• TerminologyManagement
ExchangeFormat
Organization– SiteInvestigators&EDC
ODMof“EDC”
• Workflows
• Analysis
• Search
ExchangeFormat
• StandardsManagement
• TerminologyManagement
ExchangeFormat
FDA
Organization- Sponsor
ODMof“Sponsor”
• Workflows
• Analysis
• Search
• StandardsManagement
• TerminologyManagement
ExchangeFormat
Organization- Sponsor
ODMof“Sponsor”
• Workflows
• Analysis
• Search
ExchangeFormat
• StandardsManagement
• TerminologyManagement
ExchangeFormat
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork5PointCrossLifeSciences
Keybuildingblocksofinter-organizationalworkflowsØUseExchangeStandardonlyforexchangingdata,specifications,andmodels
ØOrganizationsmustdefinethebusinessuseoftheexchangeddataanddevelopaninternalOperationalDataModelthatistunedforthatpurpose
ØEnsurethattherequiredmetadataandotherattributesthathelpmanageworkflows,decisions,orotherbusinesspurposeareincorporatedintotheODM
Ø Dataheldinsideeachorganizationservesthatorganizationusingtheapplications,workflowsandanalyticstheyneed–exchangestandardsareONLYfortransferringthedatatoanotherorganization
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork6PointCrossLifeSciences
ExchangeStandardsforData,Specifications,andModels
SubmissionPackaging
Sponsor
Sponsor
CRO
EDC
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork7PointCrossLifeSciences
• SDTM,SENDandADaM areexchangestandardsforcollecteddataoranalysisdatasets• Allowsdatatobeexchangedbetweentwoorganizations• Makesdatamachinereadable• ExchangestandardsdoNOTmakedataanalysisready– machinesatthe
receivingendneedtoreadandprocessthedata
• PRMisaexchangestandardforspecificationsofaprotocol
• SDM,CDASHandODM-XMLareexchangestandardsforstudydesigns,anddatamodelsincludingeCRF anddatamodelsforEDC
ExchangeStandardsforData,Specifications,andModels
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork8PointCrossLifeSciences
ClinicalTrials– “To-Be”
Ø CDISCstandardsallowdigitizationandstandardstructureforexchangeofspecifications,modelsanddatabetweenorganizations– workflowautomation
Ø Sponsorscatalogtrial designsandprotocolsbasedonTherapeuticAreas– workflowbetweensponsorsandCROsorsites
Ø StudyDesignsarespecifiedwithSDMreducingcostandimpactofprotocolamendments– workflowautomationbetweensponsorsandsites
Ø CRFs,eCRFs andannotatedeCRFS canbegeneratedwithautomationandCDASHtoEDCODMXML
Ø EDCODMXMLtoSDTMgeneration
Ø StandardSAP(analysisplan)scriptsorquerymaskstoselectstratifiedcohortsforanalysis
Ø Planningandpackagingofsubmissions– workflowautomation
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork9PointCrossLifeSciences
OpportunitiestoStreamlineandReduceCosts
Ø MachineReadableProtocolstoAnnotatedeCRF
Ø DataProvisioningforBiostatisticians,ScientistsandMedicalOfficers
Ø TabulationDataGeneration(ODMtoSDTM)
Ø eCRF fordesigninEDC
Ø WorkflowactionitemsinCTMS
Ø StatisticalAnalysisPlanà QueryMaskforPatientCohorts&UseofTemplatedScriptsà AnalysisDatasets
Ø Planningandpackagingofsubmissions– workflowautomation
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork10PointCrossLifeSciences
FunctionalModulesofanODM
SDESemanticDataExchange
FunnelDevelopment
Kit
Workflow&
Automation
DataRepository
(HDFS,Cassandra,Oracle)
MDRMetaDataRepository
OntologyEngine
OData,DSL
ExternalSystems
AnalyticsDataVisualization,IGO
SearchQueryMask
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StandardsManagement
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TerminologyManagement
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TerminologyManagement• Manage Terminologies
• CDISC Controlled Terminologies – Prepared and released
by CDISC
• Custom Terminologies – Sponsor defined terminologies
during standard model creation
• System codelists - Codelists utilized by system in solutions
for values in the drop downs for various modules.
• Audit Trail – Track the changes performed within the
system codelists
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RoleBasedAccessControlManagement
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ClinicalParameterSearch
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RepurposingClinicalStudyData
Informationisusedwithinaspecifictrialbutisnot(easily)availableforfurtheruse
Organizationsspendalargeamountofresourcestoacquiredatainclinicaltrials.
Courtesy:“PORTIN– agamechangertowardstranslationalresearchPortalfortranslationaldataintegration”22ndSeptember2017– 4thGlobalPrecisionMedicine&BiomarkerSummit– ChristianeUnger
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork18PointCrossLifeSciences
Whatifwewantedtoknow
In all the clinical trials we have conducted, how many individuals are there with biomarker X measurement greater than Y, and data available for clinical endpoint Z? How many of those have DNA available and consent for research use?
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork19PointCrossLifeSciences
Howmucheffortmightittake?
Forbes- CleaningBigData:MostTime-Consuming,LeastEnjoyableDataScienceTask,SurveySays
79%
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork20PointCrossLifeSciences
Wasitfun?
Forbes- CleaningBigData:MostTime-Consuming,LeastEnjoyableDataScienceTask,SurveySays
79%78%
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ClinicalTrials– As-Is
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DisparateTechniquesforDisparateSources
• Curation– insearchfor“singletruth”• Mapping– fromsourceformattoaconsumableform• Ontology– torelateinformationtootherrelatedinformation• Semanticharmonization– synonymsmakedatasearchable• Normalization– ofdatamodelsandunitsforsearchabledata• Repurposesingletruthdataintomultipleforms- kaleidoscope• Provenance– sourceororiginofdataandtimestamps• IndexingandSearch- acrossallthesingletruthdatalakes• RealTimeDataAccessRights-basedonPrivacyLaws,ICFs,andRoles• API’s– forinteroperabilitywithexternalapplications
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork23PointCrossLifeSciences
SupporttheResearchCycle
FunctionalMarkers
Omics
InformedConsent
RWD
Bio-samples
DigitalPathology
Think
Assess
Search
Find
View
Immersive,Interactive
PK/DMPK
CDMS/EDC
MedicalHistory
Registries
NonclinicalToxicology
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork24PointCrossLifeSciences
AboutPointCrossLifeSciencesØ PointCrossLifeSciencesisawhollyownedsubsidiaryofPointCrossInc.
Ø FoundedNov1999
ü Initialindustryfocus– OilandGasExplorationandProduction
ü TechnologyFocus– Bigdataanalytics,warehousingofstructuredandunstructureddata
fromnaturalprocesses
Ø BioPharmaindustryfocussince2009
Ø GlobalClients:Roche,Sanofi,Bayer,Eisai,Ipsen,J&J….
Ø Contributor,ExhibitoratIndustry
Ø FDAcontractorandprovideroftechnology
Ø Locations– FosterCity,CA,SilverSpring,MD,Paris,France,Bangalore,India
Ø Gartner“CoolVendor”inLifeSciencesin2013
Page 24
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork26PointCrossLifeSciences
PointCrossVisionfora360degreesemanticallyintegratedR&DHub
DataModel
CROInteract
StudyData Validate M5
FDAPMDA
ModelManagement
StudyLifeCycle SubmissionPlanning
ADAMSDTM
CROs,Partners
ManageTerminologies,GenerateAuditTrailReports,UserAdministration
SpecCROInter-act
StudyData Validate M4
FDAPMDA
StudySpec StudyLifeCycle SubmissionPlanning
LIMS
CROs,Partners
ManageTerminologies,GenerateAuditTrailReports,UserAdministration
CFRPart11Compliant
SEND
SDTMADaMSEND Bio
sampleBio-
Analytics
OMICS&MolecularBiomarkers
Nonclinical
Clinical
Translational
Pre-Clinical
Ontologies
Stores,UniversalDataModelbasedRepositories,SearchandIndexing
Datasources
ExternalGovernmentalandSubscriptionRegistries(NCBI,Uniprot,COSMIC…)
RealWorldDataEMR/EHR
Remote/RT/StreamingMonitoring
EDC,LegacyStudies
CIMSDSIMS
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork27PointCrossLifeSciences
Xbiom- dataandmetadatamaturationMetaDataAcquisition Metadatastorage DataExploitation
SDTMADaM
SEND(CDISC)
Biosample
Bio-Analytics
OMICS&MolecularBiomarkers
Pre- Clinical
MetadataModel
-SearchandIndexing
XbiomInsightsClinical&Biomarker
Research
XbiomInsightsNonclinical
XbiomRegulatoryClinical
XbiomRegulatoryNonclinical
EDC/CDMS
TaxonomyandUnit
Harmonization
CohortStratification
IGO
Viewer
APIs
SPECIFY
Validate
Models,MappersTerminologies
TOOLS
LegacyStudies
Remote/RT/StreamingMonitoring
ReferenceRegistries(NCBI,Uniprot,COSMIC…)
SDE Solutions
(ICF,privacy)
RealWorldData
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork28PointCrossLifeSciences
XbiomClinicalforInsightsorStudyWorkflowAutomation
ModelManagementandStudyDataSpecification
Study&SubmissionWorkflowAutomation–
FromEDCtoAnalysis
FromAnalysistoTFL
Packaging– M5eCTD
ClinicalTrialandBio-Markerwarehouse
Searchable– acrossstudies
Discoverable
AnalysisReady
VirtualStudies
StratifiedCohortSelection
Bio-SampleAvailabilitytrackingforadditionalbio-markersurveys
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork29PointCrossLifeSciences
ExchangeStandardsforData,Specifications,andModels
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork30PointCrossLifeSciences
ClinicalTrials– As-IsØ Pharmacompanies(sponsors)documentprotocolsforthetrials
Ø ThedesignofthetrialanditsorganizationisspecifiedthroughaCTMSsystemordocumented
Ø Eachtrialtendstobedesignedfromscratchwithlittletemplating - costoftrialsincrease
Ø CRFsaremanuallydesigned
Ø DatacollectedandmanagedbyCDMS
Ø Lotsofdatamanagersneededtomaintainandmaketherightdataavailabletotheprogrammersandscriptdevelopers
Ø Lotsofbio-statisticiansneededtoextractanalysisdatasetsanddoanalysisoncomputedendpoints
Ø Manuallaborintensiveworkgeneratingthetables,listing,andfigurestosupportmedicalassessmentofsafetyorefficacyandgenerationofStudyReports
©2011PointCross.AllRightsReserved.PuttingKnowledgetoWork31PointCrossLifeSciences
BuildingblocksofInter-organizationalWorkflows
OrganizationA OrganizationB
ODMof“A” ODMof“B”
• Workflows
• Analysis
• Search
• Workflows
• Analysis
• Search
ExchangeFormat
ExchangeFormat
• StandardsManagement
• TerminologyManagement
• StandardsManagement
• TerminologyManagement