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Solutions to the meet global requirements for public data disclosureAn Overview of Trial Transparency Requirements
Note about this presentation• This presentation is intended as an introduction to clinical
trial registration and results disclosure requirements. Level: BEGINNER
• This presentation is intended to provide an overview of the evolution and current state of clinical trial registration and results disclosure and regulatory requirements are paraphrased using lay language for clearer communication. However, the presentation should NOT be considered a complete or authoritative source of information.
April 15, 2010 ARMA Presentation
Agenda
April 15, 2010
• A Brief History of Clinical Trial Transparency .• Clinical Trial Transparency Requirements .• The Challenges with Trial Transparency .• The Cost of Compliance – Survey Results .• Solution Overview .
ARMA Presentation
April 15, 2010
A Brief History of Clinical Trial Transparency
Agenda
ARMA Presentation
What is a Clinical Trial• A clinical trial evaluates new therapies to test whether they are safe
and effective• Clinical Trials are generally divided into four phases:
• Phase I: Initial safety investigation and evaluating dosage ranges
• Phase II: Initial efficacy investigation and further safetyassessment
• Phase III: Extensive exploration of efficacy and safety in a largerpopulation
• Phase IV: Post market evaluation of the drug in the “real world”
• And two main types :
• Interventional: The investigators give the research subjects a particular medicine or other intervention.
• Observational: The investigators observe the subjects and measure their outcomes. The researchers do not actively manage the experiment.
April 15, 2010 ARMA Presentation
April 15, 2010
Have You Ever Participated in a Clinical Trial?
ARMA Presentation
A Problem with Transparency• Trials repeated unnecessarily, adding to patient risk
• TGN1412. In 2006, the drug caused catastrophic systemic organ failure in the trial subjects. A similar study had been conducted in 1994 (March 2006)
• Potential safety concerns or lack of efficacy not adequately reported
• Paxil – Apparent suppression of unfavorable research (2004)• Vioxx – Meta analysis published with safety concerns (November,
2004, The Lancet) and NEJM editorial (December, 2005)• Trasylol – Negative results from a retrospective study initially
withheld (September 2006)• Avanida – Meta analysis published with safety concerns (June,
2007, NEJM)
April 15, 2010 ARMA Presentation
A Problem with Perception• In 2006, only 7% percent of Americans believe that statements
made by Pharmaceutical Companies are "generally honest and trustworthy” - Harris Poll Survey in July 2006
• There was a perception that Life Sciences companies engage in selective publication:
• By not publishing Trials that don’t support the desired efficacy statements
• By not including Trials that indicate undesired adverse events in peer-review articles
• By not conducting meta-analysis across trials looking for adverse events with enough rigor
• There was a perception that the FDA was too cozy with Life Sciences companies
April 15, 2010 ARMA Presentation
Timeline – Mandatory Disclosure
April 15, 2010
1980 1990 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009
1988 Hope Act
AIDS Study Enrollment
1988 Hope Act
AIDS Study Enrollment
FDAMA 113 1997(No Registry
Available)
FDAMA 113 1997(No Registry
Available)
Clinicaltrials.gov implemented
Clinicaltrials.gov implemented
FDAMA 113(Mar 2002)
Registry Available
FDAMA 113(Mar 2002)
Registry Available
Int. LegislationSouth Africa
Int. LegislationSouth Africa
Int. LegislationItaly
Int. LegislationItaly
Maine Law
Enacted
Maine Law
Enacted
Int. LegislationIsrael
Int. LegislationIsrael
FDA-AA 2007
Title VIII
FDA-AA 2007
Title VIII
Multiple States introduce
Legislation
Multiple States introduce
Legislation
Maine RegulationMaine Regulation
Registration Required
Argentina, Brazil, Czech Republic (gov't posts, like
EudraCT)
India, France, etc.
Registration Required
Argentina, Brazil, Czech Republic (gov't posts, like
EudraCT)
India, France, etc.
EMEA
EudraCTfor Pediatric Trials
EMEA
EudraCTfor Pediatric Trials
Mandatory disclosure includes trial registration and, under some laws, results posting
ARMA Presentation
Voluntary and Mandatory Disclosure• Voluntary Disclosure
• Africa(Pan-African registry)
• Australia• China• Cuba• Germany• Japan• Netherlands
(may be mandatory soon) • Sri Lanka• UK
April 15, 2010
• Disclosure Required– Argentina– Brazil– Czech Republic– France– India– Israel– Italy– South Africa– Taiwan– US FDAMA 113 (1997) and FDAAA
(2007)
ARMA Presentation
April 15, 2010
Clinical Trial Transparency Requirements
Agenda
ARMA Presentation
Trial Registration in the US• Trials that DO require registration
• Most Phase II , III and IV drug clinical trials• Sponsors may voluntarily register trials that do not
require registration by law
• Trials that DO NOT require registration according to FDAAA
• Phase I Trials• Observational Studies
April 15, 2010 ARMA Presentation
Trial Registration in the US• State of Maine Registration of Trials
• The State of Maine has recently passed an amendment to their disclosure law that additionally requires registration of observational studies, as well as making most optional fields mandatory.
• Registration for device trials • Device trials have a slightly different definition for ‘applicable
clinical trial’. • Under FDAAA there is a special provision that allows “delayed
public disclosure” of registration information for trials for a novel device.
April 15, 2010 ARMA Presentation
Results Disclosure Status in the US• FDAAA
• Disclosure of results required for a sub-set of registered clinical trials. Results must be disclosed for all interventional trials of FDA approved marketed products.
• Note:- It is possible that results disclosure will be required for unapproved
drugs by September 27, 2010 under FDAAA
• Results Disclosure – Maine• The State of Maine has recently passed an amendment to their
own trial disclosure law that requires disclosure of results for observational trials and discontinued trials.
April 15, 2010 ARMA Presentation
Deadlines: Results• FDAAA requires results not later than 12 months after:
• The earlier of either the estimated or actual date of the last visit of the last patient specifically for purposes of data collection for the primary outcome of the trial
• Within 30 days of receiving a marketing authorization for a new drug
• Note:- Sponsor can apply for an extension in certain circumstances when
a trial is still ongoing with blinded data.
April 15, 2010 ARMA Presentation
Elements that may be added in 2010• The expansion of FDAAA, mostly for trial results
disclosure, is under consideration by US lawmakers and must be finalized by September 27, 2010.Under consideration are:
• Adding a summary of the trial and results in non-technical language.
• Adding a technical summary of the trial and results• Disclosing the full protocol or at least that information on the
protocol for the trial that may be necessary to help evaluate the results of the trial.
• Requiring results for unapproved products• Other categories as the HHS Secretary determines appropriate.
April 15, 2010 ARMA Presentation
EU Clinical Trial Results Disclosure• Legal requirement
• Disclose Results on EudraCT (EU Clinical Trials Database)
• Applies to pediatric trials (for now)• All Pediatric trials conducted in the EU or if part of a PIP• For pediatric trials, results are to be disclosed within 6 months of
study completion for both unapproved and marketed products.• For adult trials, results are to be disclosed 1 year after study
completion.
• Results to be made public sometime in early 2011
• Note: EudraCT to make protocol registration data public in Q3, 2010
April 15, 2010 ARMA Presentation
April 15, 2010
The Challenges with Trial Transparency
Agenda
ARMA Presentation
Clinical Trial Registry Landscape• Areas that influence disclosure
• Legal requirements and the registries that support their regulations such as FDAAA, Maine, EudraCT, clinicaltrials.gov.
• Policy Influences such as International Committee of Medical Journal Editors (ICMJE), WHO, WMA
• Organizational SOPs and guidelines• Institutional Review Boards (IRB) and Ethics Committees (EC)
• These four areas establish• Required data (depth and breadth of data)• Timing for submission and disclosure
• The requirements from these four may not align with one another.
April 15, 2010
Requests and interests from patient advocacy groups and the media add further
disclosure pressures
ICMJE IRB & EC
REGULATORYORGANIZATIONAL SOP
ARMA Presentation
Register Study atClinicalTrials.gov to comply with FDAAA, Maine
and ICMJE
Study Approved First Patient Enrolled
Register trial before study approval with EudraCT,
South Africa, etc.
Open New Site In US
Update Study atClinicalTrials.gov
Open New Site In EU
Update Study atClinicalTrials.gov
Register Study in local country
Study CompletePrimary Completion
Date
Submit Results at EudraCT of pediatric trials (expected by early 2011) Submit Results to
ClinicalTrials.gov
Update Study atEudraCT
Multiple Registries / Different Timelines
• Study and results data must be provided to multiple registries• Accurate and consistent data should be reported across registries.
• Registries may have different disclosure timeframes
April 15, 2010 ARMA Presentation
Complex Compliance Environment• Globally, there are many interest groups closely monitoring
clinical trials• Regulations and data requirements are frequently changing
and are not aligned internationally• Deadlines demand rapid integration of new requirements• Rules for disclosure are complex and often subject to
interpretation• Organizations may not have full control over what is
disclosed• Registration and results disclosure information remains
publicly available on clinicaltrials.gov indefinitely (including the complete record of data changes)
April 15, 2010 ARMA Presentation
Consequences for Non-Compliance• US
• FDAAA- $10,000 for first event- $10,000 per day for every day late (if not corrected within
30 days)- Public notice of failure in registry/results data bank- Withholding remaining or future grant funding (where
applicable)• State of Maine
- Barred in Maine from advertising prescription drugs on television, radio or in print
- Up to $10,000 per day
April 15, 2010 ARMA Presentation
Consequences for Non-Compliance• International
• No application possible without prior registration where trial registration is mandated
• Local IRB/ethics boards may deny approval, even in areas where registration is voluntary
• ICMJE• Unable to publish articles in peer-review journals that follow
the strict interpretation of the ICMJE rules.
April 15, 2010 ARMA Presentation
Other Non-Compliance Risks• Violation of FDA labeling and advertising regulations • Violation of the False Claims Act• Violation of SEC rule prohibiting “forward-looking
statements”• Significant restitution payments to private insurance
companies• Damage to reputation, good will and brand equity• Company placed under consent decree• In the US, Sponsors must submit Form 3674 certifying
compliance, with criminal and civil penalties for submitting a false certificate
April 15, 2010 ARMA Presentation
April 15, 2010
The Cost of Compliance
Survey Results
Agenda
ARMA Presentation
Departments Responsible for Posting
April 15, 2010
Department Primarily Responsible for RegistrationClinical OperationsRegulatory AffairsClinical Sciences / Clinical R&DMedical WritingMedical AffairsClinical Communications and Standards
Department Primarily Responsible for Results
Regulatory AffairsClinical OperationsBiostatisticsMedical and Scientific AffairsPublicationClinical R&DMedical WritingClinical Communications and Standards
ARMA Presentation
Trial Disclosure - Stakeholders
April 15, 2010 ARMA Presentation
Trial Transparency – Time Allocation
April 15, 2010 ARMA Presentation
Results Disclosure – Time Allocation
April 15, 2010 ARMA Presentation
Cost for a Typical Company
April 15, 2010 ARMA Presentation
Process# of
Processesper Month
# of Processesper Year
Cost per Year
General Administrative Tasks $75,836.14
# of new trials registration 4 43 $27,441.82
# of site/location updates 23 273 $9,433.51
# of clinical trials registration updates (excl. site/location updates)
15 180 $12,390.31
# of new trial results disclosures 3 31 $136,875.35
# of trial results disclosure updates 9 111 $117,114.81
# of ICH E3 study synopsis prepared 3 34 $35,780.29
Total Cost $414,872.24
Number of International Registries
# of additional Regs.# of Months in 2010 with new registries
Cost per Year
Additional Registries 5 6 $216,983.10Total costs in 2010 with Additional Registries $631,855.34
April 15, 2010
Solution Overview
Agenda
ARMA Presentation
Common Data Sources• Clinical Trial Management System (CTMS)/Clinical Trial
Database or Trial Spreadsheet• Protocol/Clinical Study Report
• Informed Consent Forms• Clinical Data Management System (CDMS) such as SAS• Pharmacovigilance System
April 15, 2010 ARMA Presentation
Common Requirements for a Solution• Centralized data capture and transformation for protocol
registration and results posting (automated to minimize manual data entry, ensuring ensure data integrity)
• Automated upload of protocol registration and results to registries
• A flexible platform that supports extension to international registries
• Mapping of common data elements across registry records to maximize efficiency and guarantee consistency
• Robust workflow for registration and results, including disclosure assessment, review and approval workflows
• Full audit trail & version control
April 15, 2010 ARMA Presentation
Support for Data Standards
April 15, 2010 ARMA Presentation
cd Comprehensiv e Logical Model
Entities and Roles::Access
Entities and Roles::Activ ityRoleRelationship
+ relationshipCode: PSMCodedConcept+ sequenceNumber: NUMBER+ negationIndicator: BOOLEAN+ time: TimingSpecification+ contactMediumCode: PSMCodedConcept+ targetRoleAwarenessCode: PSMCodedConcept+ signatureCode: PSMCodedConcept+ signature: PSMDescription+ slotReservationIndicator: BOOLEAN+ substitionConditionCode: PSMCodedConcept+ id: PSMID+ status: PSMCodedConcept
Entities and Roles::Dev ice
- manufacturerModelName: - softwareName: - localRemoteControlStateCode: - alertLevelCode: - lastCalibrationTime:
Entities and Roles::Employee
+ jobCode: PSMCodedConcept
Entities and Roles::Entity
+ instantiationType: ENUM {Placeholder, Actual}+ id: SET <PSMID>+ name: string+ code: PSMCodedConcept+ quantity: int+ description: PSMDescription+ statusCode: BRIDGStatus+ existenceTime: BRIDGInterval+ riskCode: PSMCodedConcept+ handlingCode: PSMCodedConcept+ contactInformation: SET <PSMContactAddr>
Entities and Roles::Liv ingEntity
+ birthTime: + sex: + deceasedInd: boolean+ deceasedTime: - multipleBirthInd: boolean- multipleBirthOrderNumber: int- organDonorInd: boolean
Entities and Roles::ManufacturedMaterial
- lotNumberText: string- expirationTime: - stabilityTime:
Entities and Roles::Material
+ formCode:
Entities and Roles::NonPersonLiv ingEntity
+ strain: - genderStatusCode:
Entities and Roles::Organization
+ geographicAddress: + electronicCommAddr: + standardIndustryClassCode:
Entities and Roles::Patient
+ confidentialityCode:
Entities and Roles::Person
+ geographicAddress: - maritalStatusCode: - educationLevelCode: + raceCode: - disabil ityCode: - l ivingArrangementCdoe: + electronicCommAddr: - religiousAffi l iationCode: + ethnicGroupCode:
Entities and Roles::Place
+ gpsText: - mobileInd: boolean- addr: - directionsText: - positionText:
Entities and Roles::
ResearchProgram
+ type:
Entities and Roles::Role
+ id: + code: PSMCodedConcept+ name: + status: + effectiveStartDate: + effectiveEndDate: + geographicAddress: + electronicCommAddr: + certificate/l icenseText:
Entities and Roles::Study
OProtocolStructure::Activ ityDeriv edData
OProtocolStructure::ElectronicSystem
OProtocolStructure::ResponsibilityAssignment
AbstractActivity
BasicTypes::RIMActivity
+ businessProcessMode: PSMBusinessProcessMode+ code: PSMCodedConcept+ derivationExpression: TEXT+ status: PSMCodedConcept+ availabilityTime: TimingSpecification+ priorityCode: PSMCodedConcept+ confidentialityCode: PSMCodedConcept+ repeatNumber: rangeOfIntegers+ interruptibleIndicator: BOOLEAN+ uncertaintyCode: CodedConcept+ reasonCode: PSMCodedConcept
BasicTypes::RIMActiv ityRelationship
+ relationshipCode: PSMCodedConcept+ sequenceNumber: NUMBER+ pauseCriterion: + checkpointCode: + splitCode: + joinCode: + negationIndicator: BOOLEAN+ conjunctionCode:
«ODM ItemData»Design Concepts::DiagnosticImage
OStudy Design and Data Collection::OEncounterDefinitionList--???
+ listOfDataCollectionInstruments:
OStudy Design and Data Collection::OBRIDGDeriv ationExpression
+ type: ENUM{transformation, selection}+ rule: TEXT+ id: PSMID+ name: TEXT
OStudy Design and Data Collection::OBRIDGTransition
+ criterion: RULE+ eventName: TEXT
Plans::Protocol/Plan
BusinessObjects::Amendment
Protocol Concepts::Bias
«implementationClass»BusinessObjects::
BusinessRule
BusinessObjects::ClinicalDev elopmentPlan
BusinessObjects::CommunicationRecord
Protocol Concepts::Concurrency
Protocol Concepts::
Configuration
Protocol Concepts::Constraint
Protocol Concepts::
Control
Protocol Concepts::DesignCharacteristic
+ synopsis: + type: test value domain = a,d,f,g+ summaryDescription: + summaryCode: + detailedMethodDescription: + detailedMethodCode:
Protocol Concepts::StudyDocument
+ effectiveEndDate: DATETIME+ version: + author: SET+ effectiveStartDate: DATETIME+ ID: SET PSMID+ documentID: + type: ENUMERATED = formal plus non...+ description: PSMDescription+ title: + status: PSMStatus+ confidentialityCode: PSMCodedConcept+ businessProcessMode: PSMBusinessProcessMode
Protocol Concepts::EligibilityCriterion
Protocol Concepts::ExclusionCriterion
BusinessObjects::IntegratedDev elopmentPlan
Design Concepts::Masking
+ level: + objectOfMasking (set): + procedureToBreak: + unmaskTriggerEvent (set):
Protocol Concepts::Milestone
BasicTypes::BRIDGAnalysisVariable
+ name: TEXT+ value: + controlledName: PSMCodedConcept+ businessProcessMode: PSMBusinessProcessMode
BasicTypes::BRIDGBusinessProcessMode
+ modeValue: ENUM {Plan, Execute}
BasicTypes::BRIDGContactAddr
+ type: PSMCodedConcept+ effectiveTime: BRIDGInterval+ usage: PSMCodedConcept
BasicTypes::BRIDGID
+ source: Text+ version: Text+ value: Text
BasicTypes::BRIDGInterv al
- startTime: timestamp+ endTime: timestamp
BasicTypes::BRIDGStatus
+ effectiveEndDate: + effectiveStartDate: + statusValue:
BusinessObjects::ProtocolRev iew
+ date: + result:
Design Concepts::Randomization
+ minimumBlockSize: + maximumBlockSize:
Protocol Concepts::
Scope
BusinessObjects::SiteStudyManagementProjectPlan
BusinessObjects::SiteSubjectManagementProjectPlan
BusinessObjects::SponsorStudyManagementProjectPlan
BusinessObjects::Study
+ startDate: Date+ endDate: Date+ type: PSMCodedConcept+ phase: PSMCodedConcept+ randomizedIndicator: Text+ SubjectType: PSMCodedConcept
Protocol Concepts::StudyBackground(why)
+ description: PSMDescription+ summaryOfPreviousFindings: PSMDescription+ summaryOfRisksAndBenefits: PSMDescription+ justificationOfObjectives: PSMDescription+ justificationOfApproach: PSMDescription+ populationDescription: PSMDescription+ rationaleForEndpoints: PSMDescription+ rationaleForDesign: PSMDescription+ rationaleForMasking: PSMDescription+ rationaleForControl: PSMDescription+ rationaleForAnalysisApproach: PSMDescription
Protocol Concepts::StudyObjectiv e(what)
+ description: PSMDescription+ intentCode: SET ENUMERATED+ objectiveType: ENUM{Primary,Secondary,Ancillary}+ id: PSMID
Protocol Concepts::StudyObjectiv eRelationship
+ type: PSMCodedConcept
Protocol Concepts::StudyObligation
+ type: ENUMERATED+ description: PSMDescription+ commissioningParty: + responsibleParty:
BusinessObjects::Activ itySchedule (the "how",
"where", "when", "who")
+ description: PSMDescription
BusinessObjects::SupplementalMaterial
+ type: + description: PSMDescription+ version: + ID: SET PSMID
Protocol Concepts::Variance
BusinessObjects::Waiv er
Name: Comprehensive Logical ModelAuthor: FridsmaVersion: 1.0Created: 7/22/2005 2:53:51 PMUpdated: 7/29/2005 2:33:32 PM
BusinessObjects::Adv erseEv entPlan
BusinessObjects::DataManagementPlan
BusinessObjects::ContingencyPlan
BusinessObjects::SubjectRecruitmentPlan
BusinessObjects::DataMonitoringCommitteePlan
BusinessObjects::SafetyMonitoringPlan
BusinessObjects::Inv estigatorRecruitmentPlan
BusinessObjects::AssayProcedures
BusinessObjects::ClinicalTrialMaterialPlans
BusinessObjects::BiospecimenPlan
BusinessObjects::ProtocolDocument
BusinessObjects::ClinicalStudyReport
BusinessObjects::EnrollmentRecord
BusinessObjects::FinalRandomizationAssignment
BusinessObjects::GuideBusinessObjects::
RandomizationAssignment
+ randomizationCode: + subjectID: + assignmentDateTime:
BusinessObjects::
RegulatoryRecord
Protocol Concepts::Outcome
- description: BRIDGDescription- ranking: OutcomeRank- associatedObjective: Set- analyticMethods: Set- asMeasuredBy: Set- outcomeVariable: - threshold:
Statistical Concepts::Hypothesis
+ statement: PSMDescription- associatedObjective: - clinicallySignificantDiff: char
AbstractActivity
Statistical Concepts::Computation
- description: PSMDescription- algorithm: char- input: AbstractStatisticalParameter- output: AbstractStatisticalParameter
Statistical Concepts::StatisticalModel
+ description: PSMDescription# outputStatistic: StudyVariable- computations: Set- assumptions: Set
Statistical Concepts::SampleSizeCalculation
+ clinicalJustification: TEXT
Statistical Concepts::AnalysisSetCriterion
- description: char- subgroupVariable: StudyDatum- sequence: int
Statistical Concepts::StatisticalAnalysisSet
+ description: PSMDescription- scopeType: AnalysisScopeTypes
Statistical Concepts::StatisticalAssumption
+ description: PSMDescription
Statistical Concepts::SequentialAnalysisStrategy
+ alphaSpendingFunction: + timingFunction: + analysis: + trialAdjustmentRule:
Statistical Concepts::StatisticalConceptArea
- evaluableSubjectDefinition: char- intentToTreatPopulation: char- clinicallyMeaningfulDifference: char- proceduresForMissingData: char- statSoftware: char- methodForMinimizingBias: char- subjectReplacementStrategy: char- randAndStratificationProcedures: char
Statistical Concepts::HypothesisTest
+ significanceLevel: double+ lowerRejectionRegion: int+ upperRejectionRegion: int+ testStatistic: + comparisonType: AnalyticComparisonTypes# associatedSummaryVariables:
AbstractActivity
Statistical Concepts::Analysis
+ description: PSMDescription+ analysisType: Set{AnalysisTypes}+ analysisRole: + rationaleForAnalysisApproach: PSMDescription# associatedStrategy: # associatedHypotheses:
Design Concepts::StudySchedule
- Periods: Set- Tasks: Set- TaskVisits: Set- associatedArms: Set
AbstractActivity
«Period»Design Concepts::Element
- Children: Set- epochType: EpochTypes
AbstractActivity
Design Concepts::PlannedTask
- displayName: char[]- whoPerforms: int- sequence: int- procDefID: PSMCodedConcept- sourceText: char[]
AbstractActivity
Design Concepts::Ev entTask
- localFacil ityType: LocalFacil ityType- centralFacil itityType: CentralFacil itiyType- eventID: OID- taskID: OID- purposes: Set
SubjectEvent
Design Concepts::ProtocolEv ent
- parent: AbstractActivity- eventType: ScheduledEventType- studyOffset: PSMInterval- studyDayOrTime: char
Design Concepts::Ev entTaskPurpose
- isBaseline: boolean- purposeType: PurposeType- associatedOutcome:
SubjectEvent
Design Concepts::UnscheduledEv ent
- eventType: UnscheduledEventType
BusinessObjects::StatisticalAnalysisPlan
Design Concepts::StudyActiv ityRef
- activityID: OID
«ODM ItemData»Design Concepts::Observ ation
- transactionType:
«ODM:ItemData»Design Concepts::
TreatmentConfirmed
«ODM:ItemDef»Design Concepts::
PlannedInterv ention
«ODM:ItemDef»Design Concepts::
PlannedObserv ation
AbstractActivity
«abstract»Design
Concepts::StudyActivityDef
«implementationClass»Design Concepts::ClinicalDecision
«implementationClass»Design Concepts::
TemporalRule
BasicTypes::StudyVariable
- OID: long- Name: char- unitOfMeasureID: OID- minValid: - maxValid: - controlledName: ENUM
BasicTypes::StudyDatum
- complete: bool- value: Value- timestamp: timestamp- itemOID:
BasicTypes::ActActRelation
- description: BRIDGDescription- relationQualifier: BRIDGCodedConcept- mode: PSMBusinessProcessMode- effectiveTime: BRIDGInterval+ priorityNumber: NUMBER- negationRule: AbstractRule- detail: char- sourceAct: AbstractActivity- destAct: AbstractActivity- sequence: int
+ «property» relationQualifier() : PSMCodedConcept+ «property» sourceAct() : AbstractActivity+ «property» destAct() : AbstractActivity
BasicTypes::AbstractRule
- isExclusive: bool
+ run() : bool
BasicTypes::AnalysisVariableInst
- roleInAnalysis: RoleInAnalysisTypes
Design Concepts::Arm
- nameOfArm: char[]- plannedEnrollmentPerArm: char[]- randomizationWeightForArn: int- associatedSchedules: Set
BasicTypes::BRIDGCodedConcept
- code: TEXT- codeSystem: - codeSystemName: TEXT- codeSystemVersion: NUMBER- displayName: TEXT- originalText: TEXT- translation: SET{PSMCodedConcept}
«ODM:ItemData»Design Concepts::
SubjectDatum
- subjectID: int
0..*
1
*
1
1..*
*
1
+source 1
+target 0..*
1 *
+correlativeStudy 0..*
+primaryStudy 1
1 *
hasAnalysisSets
*-_StatisticalAnalysisSet
hasAssumptions
hasModel
kindOfAnalysis
hasHypotheses
kindOfAnalysis
hasPurposes
hasAnalyses
kindOfActRelation
isKindOf
hasComputations
«abstraction»
1 1..*
hasAnalyses
*
-_Hypothesis
1
1..*
1-sourceobjective
*
*
+target activity
hasChildAnalyses
Defined By
-sourceactivity
*
Scheduled Sub Activities
Defined By
hasAnalysisSets
restates Objective
hasStrategy
hasElements
tasksPerformedThisSchedule
hasArms
as Measured By
hasUnscheduledEvents
hasOngoingEvents
Implements
hasCriteria
implements
«execution mode»
kindOfActivityRelation
implements
hasElements
associatedVariable
*-_DevelopmentPlan
kindOf
HasSubElements
hasSchedules
1..*
1..*
hasScheduledEvents
1
taskAtEvent
1..*
+TerminatingActivity 1..*
+EndEvent 1
+StartEvent 1
+FirstActivity 1..*
+passedTo
1+targetActivity
1+contains
1..*+IsContainedIn
1
1
1..*
1
-sourceactivity
0..*+generates
+sourceActivity
The BRIDG Model
April 15, 2010
Clinical TrialRegistration
Protocol Authoring and Documentation
Clinical Trial Design
Protocol activities and Safety monitoring (AE)
Structured Statistical Analysis
Eligibility Determination
From Douglas B. Fridsma, MD, PhD
ARMA Presentation
Structured Content ManagementPhase I-IIINon-Clinical Phase IV
Submission Planning
IND NDA Annual
Study Planning& Management
SiteManagement
Clinical DataManagement
Safety CM&C Labeling &Commercial
Data collectionRandomization
CRF Edit checksSite queries
ProtocolAuthoring &Collaboration•Objective•Stat Plan•CRF•ScheduleAmendments
StudyConcepts
BudgetFunding &Tacking
ProtocolDisclosures &
CSR Publication
IRB Approvals
CV’s
Enrollment /Consent
DMCCollaboration
Data SetsInterim Final
AggregateReporting
PSUR ASR
ExpeditedReporting
AE/SAE CaseManagement
Productmanufacture
Route
Control ofExcipientsProcedures\
validation
Control ofProduct
proceduresbatch analysis
InvestigatorBrochure
USPI/SPL
Promotional &Ads
Protocols AnalysisData Setstoxicology
pharmacokinetics
Registries and Journals
1572 Forms
Monitoring
April 15, 2010 ARMA Presentation
• How will they deal with non-US registries? …and differing US states?
• How will they keep up with rapidly evolving requirements
• How do they ensure disclosure consistency globally?• Where does the data exist inside their organization?• What validation requirements do they have?• What are the Best Disclosure Practices?• Can they support an audit of their registry and results
disclosure process?• Will they consider SaaS solutions• Is business process outsourcing an option for them?
Key Questions Companies Face
April 15, 2010 ARMA Presentation