© 2011 medidata solutions, inc. – proprietary and confidential© 2012 medidata solutions, inc....

25
© 2011 Medidata Solutions, Inc. – Proprietary and Confidential © 2012 Medidata Solutions, Inc. – Proprietary and Confidential 1 Optimizing Clinical Trials: Concept to Conclusion TM Optimizing Clinical Trials: Concept to ConclusionProtocol Representation Model (PRM) in the Real World Richard Young | Director, EMEA Monday, 17 th December, 2012

Upload: joshua-lynch

Post on 11-Jan-2016

224 views

Category:

Documents


2 download

TRANSCRIPT

Page 1: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 1Optimizing Clinical Trials: Concept to Conclusion TM

Optimizing Clinical Trials:Concept to Conclusion™

Protocol Representation Model (PRM) in the Real World

Richard Young | Director, EMEA

Monday, 17th December, 2012

Page 2: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 2Optimizing Clinical Trials: Concept to Conclusion TM

Per Patient Costs – USD ($)

Phase I Phase II Phase IIIa Phase IIIb Phase IV0

5,000

10,000

15,000

20,000

25,000

30,000

35,000

40,000

45,000

50,000

20082011

Pharmalot, reporting data from Cutting Edge Informatics, 26 Jul 2011

Page 3: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 3Optimizing Clinical Trials: Concept to Conclusion TM 3© 2011 Medidata Solutions, Inc.

Challenges of Clinical Development

Increasingly complex trials and trial design

Explosion of analytics and data related to trials

Increasing difficulty recruiting patients

Many processes continue to be siloed, manual or inefficient

Low visibility for performance management Growing importance of

emerging markets

High risks, delayed approvals, delayed

revenue

Struggle to adapt to emerging world of genomic-based drugs

Page 4: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 4Optimizing Clinical Trials: Concept to Conclusion TM

From Data to Intelligence

Confidence in DECISION

Time / ResourceRAW Data

CLEAN Data

Standard Reports

Ad hoc Reports

What Happened ?

Why ?

What Will Happen ?

Best Outcome ?

EXPLORE

PREDICT

OPTIMISE

DATA INFORMATION KNOWLEDGE INTELLIGENCE

Page 5: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 5Optimizing Clinical Trials: Concept to Conclusion TM 5© 2011 Medidata Solutions, Inc.

Protocol Representation Model

• CDISC has a standard model for the protocol• Protocol Representation Model (PRM)

• The PRM was developed to • Support the generation of a protocol document,

• Support research study (clinical trial) registration and tracking,

• Support regulatory needs,

• Facilitate single-sourced, downstream electronic consumption of the protocol content

• In SIMPLE terms, PRM enables us to• Define the core clinical components

• Define the relationship between the components

Page 6: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 6Optimizing Clinical Trials: Concept to Conclusion TM 6© 2011 Medidata Solutions, Inc.

class P...

Product

+ typeCode: CD+ classCode: SET<CD>+ pre1938Indicator: BL+ expirationDate: TS::Material+ identifier: SET<II>+ name: SET<TN>+ description: ST+ formCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

Drug

+ lotNumberText: ST+ strength: RTO<PQ,PQ>+ activeIngredientIndicator: BL::Product+ typeCode: CD+ classCode: SET<CD>+ pre1938Indicator: BL+ expirationDate: TS::Material+ identifier: SET<II>+ name: SET<TN>+ description: ST+ formCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

Device

+ reprocessedDeviceCode: CD+ availableForEvaluationIndicator: BL+ overTheCounterProductIndicator: BL+ singleUseDeviceIndicator: BL+ deviceAge: PQ+ manufactureDate: TS::Product+ typeCode: CD+ classCode: SET<CD>+ pre1938Indicator: BL+ expirationDate: TS::Material+ identifier: SET<II>+ name: SET<TN>+ description: ST+ formCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

StudyAgent

+ leadAgentIndicator: BL+ comparatorIndicator: BL+ statusCode: CD+ statusDateRange: IVL<TS>

TherapeuticAgent

+ identifier: II+ statusCode: CD+ statusDateRange: IVL<TS>

RegulatedProduct

+ approvalIdentifier: SET<II>+ authorizationTypeCode: CD+ approvalStatusCode: CD+ expandedAccessStatusCode: CD

NonTherapeuticAgent

Biologic

+ lotNumberText: ST+ strength: RTO<PQ,PQ>::Product+ typeCode: CD+ classCode: SET<CD>+ pre1938Indicator: BL+ expirationDate: TS::Material+ identifier: SET<II>+ name: SET<TN>+ description: ST+ formCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

RegulatoryApplicationSponsor

+ statusCode: CD+ statusDateRange: IVL<TS>

RegulatoryApplication

+ identifier: II+ typeCode: CD

RegulatoryAuthority

+ jurisdictionCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

Submission

+ typeCode: CD+ receiptDate: TS+ regulatoryAssessmentCode: CD+ assessmentDateRange: IVL<TS>

SubmissionUnit

+ typeCode: CD+ serialNumberText: ST+ receiptDate: TS+ statusCode: CD+ statusDateRange: IVL<TS>

«StudyRelationship»SubmissionUnitRelationship

Document

+ publicTitle: ST+ officialTitle: ST+ typeCode: CD+ publicDescription: ST+ scientificDescription: ST+ keywordCode: SET<CD>+ keywordText: SET<ST>+ text: ST+ revisionText: ST+ universalResourceLocator: URL+ bibliographicDesignation: ST+ languageCode: CD

StudyProtocol

+ acronym: ST+ phaseCode: CD+ diseaseCode: SET<CD>+ targetAnatomicSiteCode: CD+ primaryPurposeCode: CD+ purposeStatement: ST+ designConfigurationCode: CD+ studySchematic: ED+ allocationCode: CD+ confidentialityCode: CD+ populationDescription: ST+ subjectTypeCode: CD+ plannedStudySubjectExperience: ST+ acceptsHealthyVolunteersIndicator: BL+ targetAccrualNumberRange: IVL<INT>+ periodicTargetAccrualNumber: RTO<INT,PQ>+ accrualReportingMethodCode: CD+ responsiblePartyCode: CD+/ multiInstitutionIndicator: BL+ participatingOrganizationTypeCode: CD+ participatingCountryCode: SET<CD>+ AECodingSystem: CD::Document+ publicTitle: ST+ officialTitle: ST+ typeCode: CD+ publicDescription: ST+ scientificDescription: ST+ keywordCode: SET<CD>+ keywordText: SET<ST>+ text: ST+ revisionText: ST+ universalResourceLocator: URL+ bibliographicDesignation: ST+ languageCode: CD

«StudyRelationship»DocumentRelationship

OversightAuthority

Organization

+ identifier: SET<II>+ name: SET<ON>+ typeCode: CD+ description: ST+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

OversightCommittee

+ typeCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

StudySite

+ identifier: II+ leadOrganizationIndicator: BL+ reviewBoardApprovalNumberText: ST+ reviewBoardApprovalStatusCode: CD+ reviewBoardApprovalDate: TS+ targetAccrualNumber: INT+ accrualStatusCode: CD+ accrualStatusDate: TS+ dateRange: IVL<TS>+ statusCode: CD+ statusDateRange: IVL<TS>

DocumentIdentification

+ identifier: II+ primaryIndicator: BL+ typeCode: CD+ assignedDate: TS

«StudyRelationship»DocumentIdentificationRelationship

StudyOversightAuthority

Registry

+ name: ST+ acronym: ST

Activity

+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

Arm

+ name: ST+ typeCode: CD+ description: ST+ randomizationWeightText: ST

ExpandedAccessStudyProtocol

::StudyProtocol+ acronym: ST+ phaseCode: CD+ diseaseCode: SET<CD>+ targetAnatomicSiteCode: CD+ primaryPurposeCode: CD+ purposeStatement: ST+ designConfigurationCode: CD+ studySchematic: ED+ allocationCode: CD+ confidentialityCode: CD+ populationDescription: ST+ subjectTypeCode: CD+ plannedStudySubjectExperience: ST+ acceptsHealthyVolunteersIndicator: BL+ targetAccrualNumberRange: IVL<INT>+ periodicTargetAccrualNumber: RTO<INT,PQ>+ accrualReportingMethodCode: CD+ responsiblePartyCode: CD+/ multiInstitutionIndicator: BL+ participatingOrganizationTypeCode: CD+ participatingCountryCode: SET<CD>+ AECodingSystem: CD::Document+ publicTitle: ST+ officialTitle: ST+ typeCode: CD+ publicDescription: ST+ scientificDescription: ST+ keywordCode: SET<CD>+ keywordText: SET<ST>+ text: ST+ revisionText: ST+ universalResourceLocator: URL+ bibliographicDesignation: ST+ languageCode: CD

InterventionalStudyProtocol

+ numberOfInterventionGroups: INT+ interventionDescription: ST+ controlType: CD+ controlConcurrencyType: CD+ allocationCode: CD+ blindingSchemaCode: CD+ blindedRoleCode: SET<CD>::StudyProtocol+ acronym: ST+ phaseCode: CD+ diseaseCode: SET<CD>+ targetAnatomicSiteCode: CD+ primaryPurposeCode: CD+ purposeStatement: ST+ designConfigurationCode: CD+ studySchematic: ED+ allocationCode: CD+ confidentialityCode: CD+ populationDescription: ST+ subjectTypeCode: CD+ plannedStudySubjectExperience: ST+ acceptsHealthyVolunteersIndicator: BL+ targetAccrualNumberRange: IVL<INT>+ periodicTargetAccrualNumber: RTO<INT,PQ>+ accrualReportingMethodCode: CD+ responsiblePartyCode: CD+/ multiInstitutionIndicator: BL+ participatingOrganizationTypeCode: CD+ participatingCountryCode: SET<CD>+ AECodingSystem: CD::Document+ publicTitle: ST+ officialTitle: ST+ typeCode: CD+ publicDescription: ST+ scientificDescription: ST+ keywordCode: SET<CD>+ keywordText: SET<ST>+ text: ST+ revisionText: ST+ universalResourceLocator: URL+ bibliographicDesignation: ST+ languageCode: CD

Material

+ identifier: SET<II>+ name: SET<TN>+ description: ST+ formCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

ObservationalStudyProtocol

+ samplingMethodCode: CD+ timePerspectiveCode: CD::StudyProtocol+ acronym: ST+ phaseCode: CD+ diseaseCode: SET<CD>+ targetAnatomicSiteCode: CD+ primaryPurposeCode: CD+ purposeStatement: ST+ designConfigurationCode: CD+ studySchematic: ED+ allocationCode: CD+ confidentialityCode: CD+ populationDescription: ST+ subjectTypeCode: CD+ plannedStudySubjectExperience: ST+ acceptsHealthyVolunteersIndicator: BL+ targetAccrualNumberRange: IVL<INT>+ periodicTargetAccrualNumber: RTO<INT,PQ>+ accrualReportingMethodCode: CD+ responsiblePartyCode: CD+/ multiInstitutionIndicator: BL+ participatingOrganizationTypeCode: CD+ participatingCountryCode: SET<CD>+ AECodingSystem: CD::Document+ publicTitle: ST+ officialTitle: ST+ typeCode: CD+ publicDescription: ST+ scientificDescription: ST+ keywordCode: SET<CD>+ keywordText: SET<ST>+ text: ST+ revisionText: ST+ universalResourceLocator: URL+ bibliographicDesignation: ST+ languageCode: CD

OrganizationalContact

+ typeCode: SET<CD>+ primaryIndicator: BL+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

PerformedActiv ity

+ actualDateRange: IVL<TS>+ actualDuration: PQ+ effectiveDateRange: IVL<TS>+ effectiveDuration: PQ+ missedIndicator: BL+ missedReason: SET<SC>+ delayDuration: PQ::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PerformedAdministrativeActiv ity

+ varianceReason: ST::PerformedActivity+ actualDateRange: IVL<TS>+ actualDuration: PQ+ effectiveDateRange: IVL<TS>+ effectiveDuration: PQ+ missedIndicator: BL+ missedReason: SET<SC>+ delayDuration: PQ::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

Person

+ name: PN+ initials: ST+ postalAddress: AD+ telecomAddress: SET<TEL>+ educationLevelCode: CD+ academicDegree: SET<CD>+ ethnicGroupCode: SET<CD>+ raceCode: SET<CD>+ maritalStatusCode: CD+ primaryOccupationCode: CD+ occupationDateRange: IVL<TS>+ deathIndicator: BL+ statusCode: CD+ statusDateRange: IVL<TS>::BiologicEntity+ sexCode: CD+ birthOrder: INT+ birthCountryCode: CD+ birthDate: TS+ deathDate: TS

BiologicEntity

+ sexCode: CD+ birthOrder: INT+ birthCountryCode: CD+ birthDate: TS+ deathDate: TS

PlannedArm

+ targetAccrualNumber: INT::Arm+ name: ST+ typeCode: CD+ description: ST+ randomizationWeightText: ST

PlannedEligibilityCriterion

+ criterionName: ST+ requiredResponse: ST+ value: ST+ criterionCode: CD+ operator: ST+ displayOrder: INT::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PlannedObservation

::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PlannedActiv ity

+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PlannedAdministrativeActiv ity

::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

StudyLegalSponsor

+ primaryIndicator: BL

LegalSponsor

StudyReference

+ medlineIdentifierNumber: INT+ citationDescription: ST+ linkPageDescription: ST+ universalResourceLocator: URL+ resultReferenceIndicator: BL

StudyResourcing

+ activeIndicator: BL+ inactiveComment: ST

StudySiteContact

+ roleCode: CD+ primaryIndicator: BL+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

StudySiteInvestigator

::StudySiteContact+ roleCode: CD+ primaryIndicator: BL+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

StudyOutcomeMeasure

+ name: ST+ typeCode: SET<CD>+ primaryIndicator: BL+ timeFrameText: ST

StudyObjective

+ description: ST+ primaryIndicator: BL

StudyOverallStatus

+ statusCode: CD+ statusDate: TS+ anticipatedIndicator: BL+ studyStoppedReasonCode: CD+ comment: ST

StudyRecruitmentStatus

+ statusCode: CD+ statusDate: TS

View Description:This View represents the core aspects of a protocol itself, the people, organizations and the roles they may play in the context of a study.

HL7 RIM Entity

HL7 RIM Role

HL7 RIM Participation

HL7 RIM Act

HL7 RIM ActRelationship

Placeholder

Draft

Legend

IdentifiedBiologicEntity

+ identifier: II+ typeCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

ClinicalResearchStaff

+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

HealthCareProv ider

+ identifier: II+ certificateLicenseText: ST+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

HealthCareFacility

+ identifier: II+ postalAddress: AD+ statusCode: CD+ statusDateRange: IVL<TS>

ResearchOrganization

+ typeCode: CD+ statusCode: CD+ statusDateRange: IVL<TS>

ResourceProv ider

+ identifier: II+ statusCode: CD+ statusDateRange: IVL<TS>

StudyResourceProv ider

+ primaryIndicator: BL

IdentifierAssigner

PlannedExclusionCriterion

::PlannedEligibilityCriterion+ criterionName: ST+ requiredResponse: ST+ value: ST+ criterionCode: CD+ operator: ST+ displayOrder: INT::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PlannedInclusionCriterion

::PlannedEligibilityCriterion+ criterionName: ST+ requiredResponse: ST+ value: ST+ criterionCode: CD+ operator: ST+ displayOrder: INT::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

StudyRelationship

+ typeCode: CD+ inversionIndicator: BL+ contextControlCode: CD+ contextConductionIndicator: BL+ sequenceNumber: INT+ priorityNumber: INT+ pauseQuantity: PQ+ checkpointCode: CD+ splitCode: CD+ joinCode: CD+ negationIndicator: BL+ conjunctionCode: CD+ separableIndicator: BL+ subsetCode: CS+ uncertaintyCode: CD+ description: ST+ probability: REAL+ evaluableExpressionCode: CD+ comment: ST

PlannedProcedure

+ methodCode: CD+ approachSiteCode: CD+ targetSiteCode: CD+ targetSiteConditionCode: CD::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

PlannedSubstanceAdministration

+ dose: PQ+ doseDescription: ST+ doseFrequencyCode: CD+ doseRegimen: ST+ doseFormCode: CD+ doseTotal: PQ+ routeOfAdministrationCode: CD+ locationOfDoseAdministrationCode: CD+ treatmentVehicleCode: CD+ treatmentVehicleAmount: PQ::PlannedActivity+ name: SET<ST>+ actualIndicator: BL+ contingentIndicator: BL+ studyFocusIndicator: BL+ inStudySegmentPlannedActivityTypeCode: CD+ additionalDurationDescription: ST+ plannedRangeOfRepetitionsText: ST::Activity+ identifier: II+ nameCode: CD+ textDescription: ST+ categoryCode: CD+ subcategoryCode: CD+ reasonCode: SET<CD>+ statusCode: CD+ statusDateRange: IVL<TS>+ comment: ST

StudyContact

+ roleCode: SET<CD>+ primaryIndicator: BL+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

StudyInvestigator

+ identifier: II+ signatureText: ST+ dateRange: IVL<TS>::StudyContact+ roleCode: SET<CD>+ primaryIndicator: BL+ postalAddress: AD+ telecomAddress: SET<TEL>+ statusCode: CD+ statusDateRange: IVL<TS>

0..*

functions as / is represented by

0..1

1

identifies / associates to

1

0..*

oversees / isoverseen by

1

0..1

is issued by / issues

0..*

1..*

groups / is groupedby

1

1..*

is a division of /is divided into

1

0..*

performs / is performed at

0..1

1

plays / is played by

0..*

1

plays / is played by

0..1

1plays / is played by

0..*

0..1

plays / is playedby

0..1

0..1

plays / is played by

0..*

1

functions as / is represented by

0..*

1

submits / is submitted by

1

1..*

1

1

associates asubmission unitto / isassociated to asubmission unitvia

1..*

0..*

is includedin / includes

1..*

1..*

is associated to a submission via /associates a submission to 1

1..*

groups / is groupedby

0..1

1

associates to / maybe the target for0..*

1

associates from / is identified by

0..*

0..*executes/ is executed at

1

0..*

associates from / may bethe source for

1

0..*

oversees / is overseen by

0..*

1

is played by / plays

0..1

0..1

plays/ is played by

0..1

1plays / is played by0..1

1

is played by / plays

0..1

1

is scoped by / scopes

0..*

0..1

functions as / is represented by

0..*

0..1

plays / is played by

0..1

1

plays / is played by

0..*

0..1

has component /used as component0..*

1

operates as /represented by

0..*

1

provides / isprovided by 1

0..1

is issued by / issues

0..*

0..1

plays / is played by

1

1

plays / is played by

0..1

0..1

plays/ is played by

0..*

1

is played by / plays

0..*

0..*

is evaluating / is a research topic in

11

is used as / is fulfil led by

0..*

1

scopes / is scoped by

1..*

1

plays / is played by

0..1

1..*

is measured by / measures

1..*

0..1

is operationalizedby/ is described by

0..*

0..1

is responsible for /is theresponsibility of 1

1

operates as / represented by

0..*

1

plays / is played by

0..*

0..*

describes / is described by

1..*

0..*

is the resource for / is resourced by

0..*

1

is scoped by / scopes0..*

1scopes/ is scoped by

0..*

1..*

contains / iscontained in

1

1..*

describes / has

1

0..*

describes / may have

1

0..*

plays / is played by

1

0..*

scoped by / scopes

1

0..*

is scoped by / scopes

1

0..1

plays / is played by

0..1

0..*

controls / is controlled by1

0..*

is scoped by / scopes

1

0..1 plays / is played by

0..*

1..*

participates in / isconducted by

1

0..1

functions as / is represented by

0..*

0..1

functions as/ is represented by

0..*

Page 7: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 7Optimizing Clinical Trials: Concept to Conclusion TM 7© 2011 Medidata Solutions, Inc.

• Summary of Study Design (EXAMPLE)

• This is a prospective, randomized, double-blind, double-dummy, placebo

controlled, forced-titration, multicenter, parallel group trial. Stage I or II

hypertensive patients, age 18 years of age or older, who meet all other

inclusion and exclusion criteria and successfully complete the placebo run-in

period will be randomized at the site level.

Protocol Representation Model

Page 8: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 8Optimizing Clinical Trials: Concept to Conclusion TM 8© 2011 Medidata Solutions, Inc.

• Summary of Study Design (EXAMPLE)

• This is a prospective, randomized, double-blind, double-dummy, placebo

controlled, forced-titration, multicenter, parallel group trial. Stage I or II

hypertensive patients, age 18 years of age or older, who meet all other

inclusion and exclusion criteria and successfully complete the placebo run-in

period will be randomized at the site level.

Protocol Representation Model

Subject age description

Configuration

Degree of blindPopulation

disease description

Page 9: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 10Optimizing Clinical Trials: Concept to Conclusion TM 10© 2011 Medidata Solutions, Inc.

Protocol Representation Model

Page 10: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11Optimizing Clinical Trials: Concept to Conclusion TM 11© 2011 Medidata Solutions, Inc.

Objective #1

Endpoint #1

Procedure #1

Variable #1

Variable #2

Procedure #2

Variable #3

Variable #4

Objective #2

Endpoint #2

Procedure #3

Variable #5

Variable #6

Protocol Representation Model

Page 11: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 12Optimizing Clinical Trials: Concept to Conclusion TM

A New World..........

Results:

• Simplify protocols• Reduce number of procedures and cost per patient• Reduce effort setting up downstream systems• Eliminate effort associated with cleaning and analyzing

’excess’ data

• Avoid amendments/rework• Reduce cycle time (creation and review of clincial

deliverables)• Reduce duplicate data entry, reformatting and rewriting of

information

People/Behaviours: Process: Technology:

• More disciplined approach• Willingness to seek peer feedback• Business acumen - ability to

assess trade-offs bertween time cost value & risk

• Focus on outcomes & audience (start with the end in mind, consider consumers)

• Shift from study level to project level planning

• Plan -> Design -> Document• Leverage project level information• Apply study specific information• Generate clinical deliverables• Streamline review & approval

• Electronic study design tool (inc. content management capabilities and publishing templates)

• Integration with • upstream planning and study

registration solutions• downstream data collection

solutions• benchmarking data and

clinical standards

• Shift from clinical document management to information management

• Increase the quality and consistency of clinical information• Align objectives, endpoints and procedures

Strategy/Goal:

• Demonstrate traceability from strategy to plan to study design

• Support parallel development of Protocol, RAP, eCRF and CSR • Leverage industry benchmarks

Modular Authoring

Te

mp

late

s a

nd

Re

use

Fe

asi

bili

ty A

sse

ssm

en

tR

evi

ew

/ A

pp

rova

l/ D

istr

ibu

tion

Au

tho

rin

gP

lan

nin

g &

stu

dy

de

sig

n

CIL

Medidata Designer

Enter study id

1

Trigger: CIL ‘wants to’

1

Study Information Skeleton Created

Automatic

Medidata Designer

2, 3

Grow study information in Design environment

8

Medidata Designer

CIL / EST

2,3,4,5,6,7

Medidata Designer

Select delivery template(s)

9

CIL / EST

9

8,9 10

Automatic

Medidata Designer

Populate study information from Design env

Medidata Designer

CIL / EST

11

Develop WORD content within Design env

9

Templates include:- CSP- Protocol- RAP- eT&E- CSR focus document / shell- Disclosure summary (tbd)

12

CIL / EST

12

Upload deliverables to eDX for review

eDX

eDX

Approval of deliverables

Governance

eDX

13

15

12

Review of deliverables

Internal / External

14

17

IMMS

CIL / EST

PIER

16

CIL / EST

Upload approved deliverables to PIER

16

15

Upload approved deliverables to IMMS

Conduct Protocol Specific Feasibility

??

Regional Medical Director

Or does this input to WORD content?

Do we need Inc/Exc flow into eDX in order to perform

feasibility analysis (ref SB)? Or is this just manual

reference?

Draft

Final

Internal functionality not mapped: review, report, ppt

Internal references utilised in growing the information but not mapped:

- Reference content- Standard procedures

- Indicative costs

What is captured here?- new content or

- content that cannot go into design environment

IR interface for tables/listing & graphs – where?

Would details for adaptive trials have to be added here?

Trigger:1, Want wider input2, Develop WORD

content

Trigger??

Comments / Edits

Comments / Edits

‘Approved’ / FPAData Input and Output

1.Study id’s 2. Medium term study design (OneCDP)3. Study Master Data (MDM)4. Library of approved standard content (eProtocol) {All studies, Asset, study level}5. Legacy information (IMMS)6. Standard procedures (within system from MDR?)7. Indicative costs (eProtocol)8. Study information 9. Document Template Library10. Study information from design environment in template11. Additional information captured in WORD in design environment12. Draft deliverable13. Review deliverable14. Final ‘Approvable’ Deliverable15. Approved Deliverable16. Published Deliverable17 Archived Deliverable18. eDocument Metadata

2

15,16Technical Authoring Team

Store & Manage Deliverable Metadata

Medidata Designer

9

Technical Authoring Team

6

??

eProtocol, IMMS

Technical Authoring Team

Metadata Search of Ref Content for Reuse

9

eProtocol

18

2

Define Deliverables Templates

Technical Authoring Team

Copy Existing Deliverables Content: ??

??

??

Scope:Start = medium term study design onwardsEnd = approval, publishing & archiving of all study deliverables; deliverable metadata to facilitate re-use

eSignature or workflow transfer

to IMMS

Page 12: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 13Optimizing Clinical Trials: Concept to Conclusion TM

A New World Realised

PRM

Page 13: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

The Typical Protocol in 2012

• Average of 13 endpoints – 1 primary and 5 ‘key’ secondary

• Median of 170 total procedures• 85 procedures support primary and key secondary

endpoints

• Median 50 inclusion and exclusion criteria and 180+ case report form pages

• Requires study volunteers to make 11 visits over an average of 175 days

14Source: Tufts CSDD, 2012

Page 14: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

Mean Number of Data Points Collected per Study

Phase I Phase II Phase III Pase IV

110,833

378,446

929,203

675,652

15Source: Medidata Solutions Worldwide, 2012

Page 15: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

Rising Protocol Complexity and Burden (All TAs, All Phases)

00 – 03 04-07 08-11

Unique procedures per protocol (median) 20.5 28.2 30.4

Total procedures per protocol (median) 105.9 158.1 166.6

Total investigative site work burden (median units)

28.9 44.6 47.5

Total eligibility criteria 31 49 N/A

Median study duration in days 140 154 175

Median number of CRF pages per protocol 55 180 N/A

16

Getz, Campo, Kaitin. Variability in Protocol Design Complexity by Phase and Therapeutic Area. DIJ 2011 45(4); 413-420.

Source: Tufts CSDD

Page 16: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

• Ongoing shift from acute to chronic diseases

• Pipeline composition shift from traditional NCEs to biologics

• Focus on doing more in earlier development phases

• Phase IV becoming more robust and sophisticated

• Growing requirements from purchasers and payers

• Habit and legacy protocol templates and authoring practices

• Risk mitigation/risk avoidance

Primary Drivers of Protocol Complexity

Page 17: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

IMPACT: Amendment Prevalence19

Note: All values are means*Analysis excludes protocols without any amendments

Protocol Phase

Number ofAmendments*

Number of Changes

per Amendment

Phase I 2.0 5.6

Phase II 2.6 6.8

Phase III 3.6 8.5

Phase IIIb/IV 2.3 8.3

ALL PROTOCOLS 2.4 6.9

• 46% of all amendments occur BEFORE first patient first dose• 37% of all amendments are considered ‘avoidable’

Source: Tufts CSDD, 2012

Page 18: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

IMPACT: Extraneous Protocol Data

• Two primary areas of ‘protocol waste’ – (1) Essential procedures performed excessively (2) Extraneous and unused procedures

• New 2012 Tufts CSDD study among 15 participating pharmaceutical and biotechnology companies to assess cost of ‘non-core’ procedures– Study sponsored by Medidata Solutions

• N = 117 PII/III protocols; N= 22,143 procedures analyzed; cost data N=16,607 procedures

• Global, multiple therapeutic areas, No pediatric, devices, orphan diseases and No extensions

20

Page 19: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

Procedure Classifications

Core• Procedures supporting primary and/or

secondary objectives• Procedures supporting primary, *key*

secondary and safety endpoints

Non-Core• Procedures supporting tertiary and exploratory

objectives and endpoints• Procedures supporting *supportive* secondary and

exploratory endpoints• Safety and efficacy procedures that are not included

as an endpoint or objective• Procedures not tied to an endpoint or objective

Required - GCP Compliance• Screening requirements• Informed Consent• Drug dispensing (compliance)

Standard Procedures • Performed in all trials: concommitant

medications, demographics, adverse event assessment etc...

Page 20: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

One-out-of-Four Phase II/III Protocol Procedures are ‘Non-Core’

22

57.8%24.1%

8.8%

9.4%

Core NonCore Required Standard Procedures

Source: Tufts CSDD, 2012

Page 21: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

$1 Million in Direct Procedure Costs per Protocol is Paying for Non-Core Activity

Overall$000

Phase II$000

Phase III$000

All $6,001 $2,068 $9,174

Core $3,133 (52%) $1,316 (64%) $4,599 (50%)Non-Core $1,051 (18%) $262 (13%) $1,688 (18%)Required $1,372 (23%) $329 (16%) $2,214 (24%)Standard $474 (7%) $161 (8%) $673 (7%)

23

* All values are means; Aggregate of costs for all patients receiving the procedures scheduled per visit per protocol

Source: Tufts CSDD, 2012

Page 22: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

Conservative Impact of Extraneous Protocol Data Costs• The total direct cost to industry to perform ‘Non-Core procedures is an

estimated $3.7 billion annually – Only counts an investigational drug in clinical development once although it

may be in active clinical trials for multiple indications. – Counts only one clinical trial per active compound per phase when multiple

trials are likely conducted simultaneously.

• This study only examined direct procedure cost and does not include the indirect cost of personnel time to capture, monitor, clean, analyze, manage and store tertiary and exploratory procedure data.

• The ethical cost of exposing study volunteers to the risk of performing less essential, and unnecessary, procedures has also not been considered in this analysis.

24

Page 23: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 25Optimizing Clinical Trials: Concept to Conclusion TM

Page 24: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 26Optimizing Clinical Trials: Concept to Conclusion TM

Potential Financial ImpactMeasured over implementation stage

Eliminate costs

Reduce effort

Improve Quality and Consistency

Focus on Study Design

30-50% efficiency gain in protocol development process (authoring and review cycles)Sponsor experience and Medidata best practice

$150k/late phase study decrease in study costs through linking exerciseSponsor experience

$453k/per controllable amendment reductionKen Getz, Tufts Center for Study of Drug Development study results on costMedidata best practice

30-50% EDC study start-up time and effort reductionMedidata best practice

50% time saving exporting to ClinicalTrial.govSponsor and Medidata expected results

Decrease costs of collecting/storing/validating/managing unnecessary patient data$3,354/per day for 100% SDV per PICAS

Integration

Page 25: © 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 11 Optimizing Clinical Trials:

© 2011 Medidata Solutions, Inc. – Proprietary and Confidential© 2012 Medidata Solutions, Inc. – Proprietary and Confidential 29Optimizing Clinical Trials: Concept to Conclusion TM

Conclusions

• Adopting PRM, ENABLES• Significant process change involved in adoption• Real business value can be demonstrated• Opportunity to

• Influence trial cost and complexity• Drive reuse and efficiency• Interface with other standards

• Application of standards will enable organizations to build BI and analytic capability never possible before

• Adopting PRM, WILL• Drive significant operational, clinical, ethical and technical savings/benefits