Standards and Ontology-driven Workflow Automation of ... SDE/Zabrowski.pdf · Standards and Ontology-driven Workflow Automation of Clinical Studies . PointCross Life Sciences 2 Putting

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StandardsandOntology-drivenWorkflowAutomationofClinicalStudies

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• Multiplelaboratories,investigationsitesandcontractresearchorganizationsareinvolved--- Workflowsareinter-organizational

• Expensiveandverytimeconsumingdatamanagement,programmingandstatisticalanalysiseffort--- 75%to80%oftimeisspentwithwranglingwithdatatogetittothepointwherestatisticalanalysiscanbeperformed*1*2

• Regulatedanddesignedforsubmissiontoregulatoryagencies--- GCP,GLP

• RecentmandatesrequirethatthecollecteddatabeorganizedunderCDISCexchangestandardsandanalysisdatasetsbesubmittedinADaM --- Digitaldatainstandardformatsareheretostay.

• NewStudyProtocolsandProtocolAmendmentsareexpensiveandaddsignificanttimetothelifecycleofstudies--- cantheirproductionbestreamlined.

CharacteristicsoftheClinicalTrialWorkflow


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


ChainingblocksofInter-OrganizationalWorkflows

Organization- CRO

ODMof“CRO”

• Workflows

• Analysis

• Search

ExchangeFormat

• StandardsManagement

• TerminologyManagement

ExchangeFormat

Organization– SiteInvestigators&EDC

ODMof“EDC”

• Workflows

• Analysis

• Search

ExchangeFormat



ExchangeFormat

FDA

Organization- Sponsor

ODMof“Sponsor”

• Workflows

• Analysis

• Search



ExchangeFormat

Organization- Sponsor

ODMof“Sponsor”

• Workflows

• Analysis

• Search

ExchangeFormat



ExchangeFormat


Keybuildingblocksofinter-organizationalworkflowsØUseExchangeStandardonlyforexchangingdata,specifications,andmodels

ØOrganizationsmustdefinethebusinessuseoftheexchangeddataanddevelopaninternalOperationalDataModelthatistunedforthatpurpose

ØEnsurethattherequiredmetadataandotherattributesthathelpmanageworkflows,decisions,orotherbusinesspurposeareincorporatedintotheODM

Ø Dataheldinsideeachorganizationservesthatorganizationusingtheapplications,workflowsandanalyticstheyneed–exchangestandardsareONLYfortransferringthedatatoanotherorganization


ExchangeStandardsforData,Specifications,andModels

SubmissionPackaging

Sponsor

Sponsor

CRO

EDC


• SDTM,SENDandADaM areexchangestandardsforcollecteddataoranalysisdatasets• Allowsdatatobeexchangedbetweentwoorganizations• Makesdatamachinereadable• ExchangestandardsdoNOTmakedataanalysisready– machinesatthe

receivingendneedtoreadandprocessthedata

• PRMisaexchangestandardforspecificationsofaprotocol

• SDM,CDASHandODM-XMLareexchangestandardsforstudydesigns,anddatamodelsincludingeCRF anddatamodelsforEDC



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


OpportunitiestoStreamlineandReduceCosts

Ø MachineReadableProtocolstoAnnotatedeCRF

Ø DataProvisioningforBiostatisticians,ScientistsandMedicalOfficers

Ø TabulationDataGeneration(ODMtoSDTM)

Ø eCRF fordesigninEDC

Ø WorkflowactionitemsinCTMS

Ø StatisticalAnalysisPlanà QueryMaskforPatientCohorts&UseofTemplatedScriptsà AnalysisDatasets

Ø Planningandpackagingofsubmissions– workflowautomation


FunctionalModulesofanODM

SDESemanticDataExchange

FunnelDevelopment

Kit

Workflow&

Automation

DataRepository

(HDFS,Cassandra,Oracle)

MDRMetaDataRepository

OntologyEngine

OData,DSL

ExternalSystems

AnalyticsDataVisualization,IGO

SearchQueryMask


StandardsManagement


TerminologyManagement


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


RoleBasedAccessControlManagement



ClinicalParameterSearch


RepurposingClinicalStudyData

Informationisusedwithinaspecifictrialbutisnot(easily)availableforfurtheruse

Organizationsspendalargeamountofresourcestoacquiredatainclinicaltrials.

Courtesy:“PORTIN– agamechangertowardstranslationalresearchPortalfortranslationaldataintegration”22ndSeptember2017– 4thGlobalPrecisionMedicine&BiomarkerSummit– ChristianeUnger


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?


Howmucheffortmightittake?

Forbes- CleaningBigData:MostTime-Consuming,LeastEnjoyableDataScienceTask,SurveySays

79%


Wasitfun?

Forbes- CleaningBigData:MostTime-Consuming,LeastEnjoyableDataScienceTask,SurveySays

79%78%


ClinicalTrials– As-Is


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


SupporttheResearchCycle

FunctionalMarkers

Omics

InformedConsent

RWD

Bio-samples

DigitalPathology

Think

Assess

Search

Find

View

Immersive,Interactive

PK/DMPK

CDMS/EDC

MedicalHistory

Registries

NonclinicalToxicology


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


SupplementalSlides


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


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


XbiomClinicalforInsightsorStudyWorkflowAutomation

ModelManagementandStudyDataSpecification

Study&SubmissionWorkflowAutomation–

FromEDCtoAnalysis

FromAnalysistoTFL

Packaging– M5eCTD

ClinicalTrialandBio-Markerwarehouse

Searchable– acrossstudies

Discoverable

AnalysisReady

VirtualStudies

StratifiedCohortSelection

Bio-SampleAvailabilitytrackingforadditionalbio-markersurveys




ClinicalTrials– As-IsØ Pharmacompanies(sponsors)documentprotocolsforthetrials

Ø ThedesignofthetrialanditsorganizationisspecifiedthroughaCTMSsystemordocumented

Ø Eachtrialtendstobedesignedfromscratchwithlittletemplating - costoftrialsincrease

Ø CRFsaremanuallydesigned

Ø DatacollectedandmanagedbyCDMS

Ø Lotsofdatamanagersneededtomaintainandmaketherightdataavailabletotheprogrammersandscriptdevelopers

Ø Lotsofbio-statisticiansneededtoextractanalysisdatasetsanddoanalysisoncomputedendpoints

Ø Manuallaborintensiveworkgeneratingthetables,listing,andfigurestosupportmedicalassessmentofsafetyorefficacyandgenerationofStudyReports


BuildingblocksofInter-organizationalWorkflows

OrganizationA OrganizationB

ODMof“A” ODMof“B”

• Workflows

• Analysis

• Search

• Workflows

• Analysis

• Search

ExchangeFormat

ExchangeFormat





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Standards and Ontology-driven Workflow Automation of ... SDE/Zabrowski.pdf · Standards and Ontology-driven Workflow Automation of Clinical Studies . PointCross Life Sciences 2 Putting