solutions to the meet global requirements for public data disclosure an overview of trial...

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

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)


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


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


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.


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.


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.


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.


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

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


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)


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


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.


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

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


Trial Transparency – Time Allocation


Results Disclosure – Time Allocation


Cost for a Typical Company


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


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


Support for Data Standards


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


• 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


Thomas Wicks

Intrasphere Technologies

(212)[email protected]

solutions to the meet global requirements for public data disclosure an overview of trial...

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