Solutions to the meet global requirements
for public data disclosure
An 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
•
A Brief History of Clinical Trial Transparency
• Clinical Trial Transparency Requirements
• The Challenges with Trial Transparency
• The Cost of Compliance – Survey Results
• Solution Overview
April 15, 2010
ARMA Presentation
.
.
.
.
.
A Brief History of Clinical Trial Transparency
Agenda
April 15, 2010
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 safety
assessment
•
Phase III:
Extensive exploration of efficacy and safety in a larger
population
•
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
Have You Ever Participated in a Clinical
Trial?
April 15, 2010
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
Maine Law
Enacted
FDAMA 113
(Mar 2002)
Registry Available
FDAMA 113 1997
(No Registry
Available)
1988 Hope Act
AIDS Study
Enrollment
1980
Clinicaltrials.gov
implemented
1990
2000
2001
2002
2003
2004
Int. Legislation
Israel
Maine Regulation
Int. Legislation
South Africa
FDA-AA 2007
Title VIII
Int. Legislation
Italy
Multiple States
introduce
Legislation
2005
2006
2007
Registration
Required
Argentina, Brazil,
Czech Republic
(gov't posts, like
EudraCT)
India, France, etc.
EMEA
EudraCT
for Pediatric Trials
2008
2009
Mandatory disclosure includes trial registration and, under some laws, results posting
April 15, 2010
ARMA Presentation
Voluntary and Mandatory Disclosure
•
Voluntary Disclosure
•
•
•
•
•
•
•
•
•
•
Disclosure Required
Africa
(Pan-African registry)
Australia
China
Cuba
Germany
Japan
Netherlands
(may be mandatory soon)
Sri Lanka
UK
April 15, 2010
ARMA Presentation
–
–
–
–
–
–
–
–
–
–
Argentina
Brazil
Czech Republic
France
India
Israel
Italy
South Africa
Taiwan
US FDAMA 113 (1997) and FDAAA
(2007)
Clinical Trial Transparency Requirements
Agenda
April 15, 2010
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
The Challenges with Trial Transparency
Agenda
April 15, 2010
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
ORGANIZATIONAL SOP
ICMJE
REGULATORY
IRB & EC
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
ARMA Presentation
Requests and interests from patient
advocacy groups and the media add further
disclosure pressures
Multiple Registries / Different Timelines
Update Study at
EudraCT
Register trial before study
approval with EudraCT,
South Africa, etc.
Study Approved
Register Study at
ClinicalTrials.gov
to comply with
FDAAA, Maine
and ICMJE
First Patient Enrolled
Register Study in
local country
Update Study at
ClinicalTrials.gov
Open New Site In US
• Study
Update Study at
ClinicalTrials.gov
Open New Site In EU
Submit Results
at EudraCT of
pediatric trials
(expected by
early 2011)
Submit Results to
ClinicalTrials.gov
Study Complete
Primary Completion
Date
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
The Cost of Compliance
Survey Results
Agenda
April 15, 2010
ARMA Presentation
Departments Responsible for Posting
Department Primarily Responsible for Registration
Clinical Operations
Regulatory Affairs
Clinical Sciences / Clinical R&D
Medical Writing
Medical Affairs
Clinical Communications and Standards
Department Primarily Responsible for Results
Regulatory Affairs
Clinical Operations
Biostatistics
Medical and Scientific Affairs
Publication
Clinical R&D
Medical Writing
Clinical Communications and Standards
April 15, 2010
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
# of
Processes
per Month
Process
# of
Processes
per Year
General Administrative Tasks
Cost per
Year
$75,836.14
# of new trials registration
4
43
$27,441.82
23
273
$9,433.51
15
180
$12,390.31
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
# of site/location updates
# of clinical trials registration updates (excl. site/location
updates)
# of new trial results disclosures
Number of
International
Registries
Additional Registries
April 15, 2010
# of additional Regs.
# of Months in 2010
with new registries
5
6
Total costs in 2010 with Additional Registries
ARMA Presentation
Cost per Year
$216,983.10
$631,855.34
Solution Overview
Agenda
April 15, 2010
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
Clinical Trial Design
Protocol Authoring
and Documentation
The BRIDG Model
cd Comprehensiv e Logical Model
Design Concepts::Masking
+
+
+
+
level:
objectOfMasking (set):
procedureToBreak:
unmaskTriggerEvent (set):
Protocol
Concepts::
Control
HasSubElements
AbstractActivity
«Period»
Design Concepts::Element
Protocol Concepts::DesignCharacteristic
Name:
Author:
Version:
Created:
Updated:
Comprehensive Logical Model
Fridsma
1.0
7/22/2005 2:53:51 PM
7/29/2005 2:33:32 PM
+
+
+
+
+
+
Protocol
Concepts::
Scope
-
Protocol
Concepts::
Configuration
synopsis:
type: test value domain = a,d,f,g
summaryDescription:
summaryCode:
detailedMethodDescription:
detailedMethodCode:
Children: Set
epochType: EpochTypes
AbstractActivity
Clinical Trial
Registration
hasElements
hasScheduledEvents
Design Concepts::PlannedTask
-
Protocol
Concepts::Bias
displayName: char[]
whoPerforms: int
sequence: int
procDefID: PSMCodedConcept
sourceText: char[]
SubjectEvent
Protocol Concepts::StudyBackground(w hy)
+
+
+
+
+
+
+
+
+
+
+
Design Concepts::Arm
Design Concepts::ProtocolEv ent
description: PSMDescription
summaryOfPreviousFindings: PSMDescription
summaryOfRisksAndBenefits: PSMDescription
justificationOfObjectives: PSMDescription
justificationOfApproach: PSMDescription
populationDescription: PSMDescription
rationaleForEndpoints: PSMDescription
rationaleForDesign: PSMDescription
rationaleForMasking: PSMDescription
rationaleForControl: PSMDescription
rationaleForAnalysisApproach: PSMDescription
hasElements
Protocol Concepts::StudyObligation
+
+
+
+
1
type: ENUMERATED
description: PSMDescription
commissioningParty:
responsibleParty:
Design Concepts::
Randomization
+
+
Protocol Concepts::
Concurrency
-
-
parent: AbstractActivity
eventType: ScheduledEventType
studyOffset: PSMInterval
studyDayOrTime: char
nameOfArm: char[]
plannedEnrollmentPerArm: char[]
randomizationWeightForArn: int
associatedSchedules: Set
tasksPerformedThisSchedule
taskAtEvent
hasOngoingEvents
minimumBlockSize:
maximumBlockSize:
1..*
AbstractActivity
+correlativeStudy 0..*
Design Concepts::Ev entTask
BusinessObj ects::Study
BusinessObj ects::
ClinicalDev elopmentPlan
-_DevelopmentPlan
+
+
+
+
+
+
BusinessObj ects:
:Amendment
*
-
+primaryStudy 1
startDate: Date
endDate: Date
type: PSMCodedConcept
phase: PSMCodedConcept
randomizedIndicator: Text
SubjectType: PSMCodedConcept
hasArms
Design Concepts::StudySchedule
localFacilityType: LocalFacilityType
centralFacilitityType: CentralFacilitiyType
eventID: OID
taskID: OID
purposes: Set
-
Periods: Set
Tasks: Set
TaskVisits: Set
associatedArms: Set
hasUnscheduledEvents
BusinessObj ects::
IntegratedDev elopmentPlan
Protocol Concepts::StudyObj ectiv e(w hat)
+
+
+
+
1
+
SubjectEvent
Design Concepts::UnscheduledEv ent
BusinessObj ects::
Activ itySchedule (the "how ",
"w here", "w hen", "w ho")
-
eventType: UnscheduledEventType
-
activityID: OID
description: PSMDescription
description: PSMDescription
intentCode: SET ENUMERATED
objectiveType: ENUM{Primary,Secondary,Ancillary}
id: PSMID
hasPurposes
«execution mode»
*
Design Concepts::
StudyActiv ityRef
Scheduled Sub Activities
0..*
-source
objective
Protocol Concepts::StudyDocument
+
+
+
+
+
+
+
+
+
+
+
+
1
1..*
Protocol Concepts::Outcome
BusinessObj ects::
ProtocolDocument
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
1..* -
BusinessObj ects::
ClinicalStudyReport
description: BRIDGDescription
ranking: OutcomeRank
associatedObjective: Set
analyticMethods: Set
asMeasuredBy: Set
outcomeVariable:
threshold:
Defined By
as Measured By
-
Design Concepts::Ev entTaskPurpose
BasicTypes::StudyDatum
isBaseline: boolean
purposeType: PurposeType
associatedOutcome:
-
BusinessObj ects::
CommunicationRecord
+
type:
+target 0..*
Defined By
+
+
+
+
-
-
«ODM ItemData»
Design Concepts::
DiagnosticImage
subjectID: int
BasicTypes::StudyVariable
-
«ODM:ItemData»
Design Concepts::
TreatmentConfirmed
Statistical Concepts::StatisticalConceptArea
Entities and Roles::Organization
+
+
+
instantiationType: ENUM {Placeholder, Actual}
id: SET <PSMID>
1
name: string
code: PSMCodedConcept
quantity: int
description: PSMDescription
statusCode: BRIDGStatus
1
existenceTime: BRIDGInterval
riskCode: PSMCodedConcept
handlingCode: PSMCodedConcept
contactInformation: SET <PSMContactAddr>
BusinessObj ects::
StatisticalAnalysisPlan
*
1
Entities and Roles::Role
* +
+
+
+
+
+
+
+
+
Entities and Roles::Activ ityRoleRelationship
id:
code: PSMCodedConcept
name:
status:
effectiveStartDate:
effectiveEndDate:
geographicAddress:
electronicCommAddr:
certificate/licenseText:
+
+
+
+
+
* +
+
+
+
+
+
+
1
geographicAddress:
electronicCommAddr:
standardIndustryClassCode:
1
birthTime:
sex:
deceasedInd: boolean
deceasedTime:
multipleBirthInd: boolean
multipleBirthOrderNumber: int
organDonorInd: boolean
+
hasHypotheses
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::
ManufacturedMaterial
Entities and Roles::
Access
Entities and Roles::Person
significanceLevel: double
lowerRejectionRegion: int
upperRejectionRegion: int
testStatistic:
comparisonType: AnalyticComparisonTypes
associatedSummaryVariables:
BasicTypes::ActActRelation
hasAnalysisSets
hasAnalyses
geographicAddress:
maritalStatusCode:
educationLevelCode:
raceCode:
disabilityCode:
livingArrangementCdoe:
electronicCommAddr:
religiousAffiliationCode:
ethnicGroupCode:
«property» relationQualifier() : PSMCodedConcept
«property» sourceAct() : AbstractActivity
«property» destAct() : AbstractActivity
kindOfActRelation
kindOfAnalysis
kindOfAnalysis
-_StatisticalAnalysisSet
*
Protocol Concepts::StudyObj ectiv eRelationship
+
type: PSMCodedConcept
statement: PSMDescription
associatedObjective:
clinicallySignificantDiff: char
*
Statistical Concepts::
StatisticalAssumption
AbstractActivity
-_Hypothesis
*
hasAnalyses
+
BasicTypes::
AbstractRule
description: PSMDescription
Statistical Concepts::Analysis
+
+
+
+
#
#
description: PSMDescription
analysisType: Set{AnalysisTypes}
analysisRole:
rationaleForAnalysisApproach: PSMDescription
associatedStrategy:
associatedHypotheses:
hasStrategy
-
isExclusive: bool
+
run() : bool
hasAssumptions
hasModel
Statistical Concepts::StatisticalModel
+
#
-
description: PSMDescription
outputStatistic: StudyVariable
computations: Set
assumptions: Set
implements
Implements
implements
hasComputations
Entities and Roles::Dev ice
-
+
+
+
clinicalJustification: TEXT
Statistical Concepts::Hypothesis
+
-
hasChildAnalyses
strain:
genderStatusCode:
description: BRIDGDescription
relationQualifier: BRIDGCodedConcept
mode: PSMBusinessProcessMode
effectiveTime: BRIDGInterval
priorityNumber: NUMBER
negationRule: AbstractRule
detail: char
sourceAct: AbstractActivity
destAct: AbstractActivity
sequence: int
AbstractActivity
businessProcessMode: PSMBusinessProcessMode
code: PSMCodedConcept
derivationExpression: TEXT
status: PSMCodedConcept
+TerminatingActivity 1..*
availabilityTime: TimingSpecification
priorityCode: PSMCodedConcept
confidentialityCode: PSMCodedConcept
repeatNumber: rangeOfIntegers
+EndEvent 1
interruptibleIndicator: BOOLEAN
uncertaintyCode: CodedConcept
+StartEvent 1
reasonCode: PSMCodedConcept
Entities and Roles::
NonPersonLiv ingEntity
+
-
+
-
Statistical Concepts::
SampleSizeCalculation
+FirstActivity 1..*
+
+
+
+
description: char
subgroupVariable: StudyDatum
sequence: int
+
BasicTypes::RIMActivity
+
+
+
+
+
+
+
+
+
+
+
confidentialityCode:
OProtocolStructure::
ElectronicSystem
lotNumberText: string
expirationTime:
stabilityTime:
description: PSMDescription
scopeType: AnalysisScopeTypes
hasCriteria
-source
activity
+target activity
-source
activity
1
-
+
-
Statistical Concepts::HypothesisTest
+
+
+
+
+
#
jobCode: PSMCodedConcept
Entities and Roles::Patient
+
«ODM:ItemDef»
Design Concepts::
PlannedObserv ation
Statistical Concepts::
StatisticalAnalysisSet
hasAnalysisSets
evaluableSubjectDefinition: char
intentToTreatPopulation: char
clinicallyMeaningfulDifference: char
proceduresForMissingData: char
statSoftware: char
methodForMinimizingBias: char
subjectReplacementStrategy: char
randAndStratificationProcedures: char
Statistical Concepts::AnalysisSetCriterion
Entities and Roles::Employee
+
formCode:
-
-
1..*
Entities and
Roles::Material
Entities and Roles::Liv ingEntity
+
+
+
+
-
OID: long
Name: char
unitOfMeasureID: OID
minValid:
maxValid:
controlledName: ENUM
restates Objective
*
1..*
+
+
+
+
+
+
+
+
+
+
+
kindOfActivityRelation
relationshipCode: PSMCodedConcept
sequenceNumber: NUMBER
pauseCriterion:
checkpointCode:
splitCode:
joinCode:
negationIndicator: BOOLEAN
conjunctionCode:
Entities and Roles::Entity
gpsText:
mobileInd: boolean
addr:
directionsText:
positionText:
roleInAnalysis: RoleInAnalysisTypes
transactionType:
BasicTypes::RIMActiv ityRelationship
+
+
+
+
+
+
+
+
Entities and Roles::Place
«ODM:ItemDef»
Design Concepts::
PlannedInterv ention
kindOf
«abstract»
Design
Concepts::
StudyActivityDef
«ODM:ItemData»
Design Concepts::
SubjectDatum
-
type:
description: PSMDescription
version:
ID: SET PSMID
Entities and Roles::
Study
+
-
AbstractActivity
isKindOf
BasicTypes::AnalysisVariableInst
associatedVariable
«ODM ItemData»
Design Concepts::Observ ation
BusinessObj ects::
SupplementalMaterial
+source 1
Entities and
Roles::
ResearchProgram
complete: bool
value: Value
timestamp: timestamp
itemOID:
*
manufacturerModelName:
softwareName:
localRemoteControlStateCode:
alertLevelCode:
lastCalibrationTime:
+IsContainedIn
+contains 1
OProtocolStructure::
ResponsibilityAssignment
1
1..* +targetActivity
+sourceActivity 1
«implementationClass»
Design Concepts::
TemporalRule
Statistical Concepts::
SequentialAnalysisStrategy
+
+
+
+
alphaSpendingFunction:
timingFunction:
analysis:
trialAdjustmentRule:
AbstractActivity
«implementationClass»
BusinessObj ects::
BusinessRule
«implementationClass»
Design Concepts::
ClinicalDecision
Statistical Concepts::Computation
-
description: PSMDescription
algorithm: char
input: AbstractStatisticalParameter
output: AbstractStatisticalParameter
+passedTo
+generates 0..*
OProtocolStructure::
Activ ityDeriv edData
hasSchedules
Plans::Protocol/Plan
BusinessObj ects::
SiteSubj ectManagementProj ectPlan
1..*
1
OStudy Design and Data Collection::
OBRIDGDeriv ationExpression
BasicTypes::BRIDGInterv al
BasicTypes::BRIDGBusinessProcessMode
+
modeValue: ENUM {Plan, Execute}
+
startTime: timestamp
endTime: timestamp
+
+
+
+
BusinessObj ects::
RandomizationAssignment
OStudy Design and Data Collection::OBRIDGTransition
BasicTypes::BRIDGID
+
+
+
source: Text
version: Text
value: Text
+
+
criterion: RULE
eventName: TEXT
+
+
+
+
name: TEXT
value:
controlledName: PSMCodedConcept
businessProcessMode: PSMBusinessProcessMode
code: TEXT
codeSystem:
codeSystemName: TEXT
codeSystemVersion: NUMBER
displayName: TEXT
originalText: TEXT
translation: SET{PSMCodedConcept}
+
+
+
BusinessObj ects::
EnrollmentRecord
randomizationCode:
subjectID:
assignmentDateTime:
BusinessObj ects::Guide
BasicTypes::BRIDGContactAddr
«abstraction»
+
+
+
type: PSMCodedConcept
effectiveTime: BRIDGInterval
usage: PSMCodedConcept
BusinessObj ects::BiospecimenPlan
BusinessObj ects::AssayProcedures
BusinessObj ects::
Waiv er
OStudy Design and Data Collection::
OEncounterDefinitionList--???
effectiveEndDate:
effectiveStartDate:
statusValue:
BusinessObj ects::
ClinicalTrialMaterialPlans
BusinessObj ects::
DataMonitoringCommitteePlan
BusinessObj ects::
FinalRandomizationAssignment
Protocol Concepts::Constraint
BasicTypes::BRIDGStatus
+
+
+
1 1..*
BusinessObj ects::Inv estigatorRecruitmentPlan
BusinessObj ects::
DataManagementPlan
BasicTypes::BRIDGAnalysisVariable
BasicTypes::BRIDGCodedConcept
-
Structured
Statistical Analysis
BusinessObj ects:
:
RegulatoryRecord
type: ENUM{transformation, selection}
rule: TEXT
id: PSMID
name: TEXT
BusinessObj ects::
SiteStudyManagementProj ectPlan
BusinessObj ects::
SponsorStudyManagementProj ectPlan
+
Protocol Concepts::
EligibilityCriterion
listOfDataCollectionInstruments:
Protocol Concepts::
Variance
Protocol Concepts::
ExclusionCriterion
BusinessObj ects:
:ProtocolRev iew
+
+
date:
result:
Protocol Concepts::
Milestone
Protocol activities and
Safety monitoring (AE)
Eligibility
Determination
BusinessObj ects::
Adv erseEv entPlan
BusinessObj ects::
ContingencyPlan
BusinessObj ects::
Subj ectRecruitmentPlan
BusinessObj ects::SafetyMonitoringPlan
From Douglas B. Fridsma, MD, PhD
April 15, 2010
ARMA Presentation
Structured Content Management
Non-Clinical
Phase I-III
Phase IV
Submission Planning
IND
Protocols Analysis
Data Sets
toxicology
pharmacokinetics
Registries and Journals
Study Planning
& Management
Study
Concepts
Protocol
Authoring &
Collaboration
•Objective
•Stat Plan
•CRF
•Schedule
Amendments
Annual
Site
Management
Clinical Data
Management
Safety
CM&C
IRB Approvals
Data collection
Randomization
CRF Edit checks
Site queries
AE/SAE Case
Management
Product
manufacture
Route
USPI/SPL
1572 Forms
Data Sets
Interim Final
Expedited
Reporting
Control of
Excipients
Procedures\
validation
Promotional &
Ads
CV’s
DMC
Collaboration
Aggregate
Reporting
PSUR ASR
Control of
Product
procedures
batch analysis
Investigator
Brochure
Budget
Funding &
Tacking
Enrollment /
Consent
Protocol
Disclosures &
CSR Publication
Monitoring
April 15, 2010
NDA
ARMA Presentation
Labeling &
Commercial
Key Questions Companies Face
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?
•
April 15, 2010
ARMA Presentation
Thomas Wicks
Intrasphere Technologies
(212)937-8225
thomas.wicks@intrasphere.com