Secure Interim Analysis Data Access and Automated … · 2017-10-08 · Secure Interim Analysis...
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Secure Interim Analysis Data Access and Automated DMC/DSMB Management with ACES® Eric J. Silva, Cytel, Inc. Steven Ketchum, Ph.D., Sunesis Pharmaceuticals
Transcript of Secure Interim Analysis Data Access and Automated … · 2017-10-08 · Secure Interim Analysis...
SecureInterimAnalysisDataAccessandAutomatedDMC/DSMBManagementwithACES
EricJ.Silva,Cytel,Inc.StevenKetchum,Ph.D.,SunesisPharmaceuticals
14-Dec-2011 2011 Cytel, Inc. and Sunesis. All Rights Reserved. 2
Introductions: Todays Speakers
EricJ.SilvaManager,EnterpriseandHostedSolutionsCytel,[email protected]
StevenKetchum,Ph.D.Sr.VicePresident,R&D
www.sunesis.com
TheconsiderationswhenforminginformationpathsforDMC/DSMBcommunications
Schedulinganinterimanalysis whenisbest?
Howtobuildfirewallstoprotectinterimdata
Whatcanyoudotobuildregulatorytrust?
Howtoautomategenerationofsupportingdocumentationneededforinterimanalysis
HowisACESbeingusedtoday?
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What You Will Learn
Background
TraditionalProcessConcerns
DMC/DSMBCommunications
PlanningInterimAnalyses
WhereDoesACESFitIn?
ActualandPotentialBenefits
ClosingRemarks
Q&A
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Agenda
Safetymonitoringisrequired
RoleofDMCsisexpandingandbecomingmorecomplex
TraditionalDMCresponsibilities
AdaptivedesignclinicaltrialsincreaseDMCresponsibility
Adaptivedesignrequiresacommunicationplanthatallowsfortrialmodificationsafterinterimanalyses
Background
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Overthepast10years,therehasbeenansignificantincreaseintheuseofDataMonitoringCommittees.
Sponsor
IndependentStatisticalCenter(ISC)
DataMonitoringCommittee(DMC)DataMonitoringSafetyBoard(DSMB)
SteeringCommittee
IVRS
EDC
DrugSupply
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Key Roles in Interim Analyses
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Traditional Process
)
CreateDocuments(Protocol,SAP,DMCCharter)
Store/ArchiveDocuments
EnrollSubjects&Collect
Responses
SendResponseDatatoISC
PerformAnalysisand
CreateReports
SendAnalysistoDMC
Spo
nsor
ISC
DM
C MakeRecommendation
SendRecommendation
toSponsor/Steering
Committee
MakeDecision
AboutTrial
Ste
erin
gC
omm
ittee Afterdecision
1.DMCnotified2.DrugSupplynotified3.IVRSnotified
Create andTestAnalysisPrograms
Request additional information
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SOPTrainingandEnforcement
FirewallImplementation
OperationalBias UnblindedAnalyses
BlindMaintenance
AssurancesofLimitation SponsorInvolvement
SteeringCommitteeInvolvement
LackofConsistency Process Notifications Snapshots
InterimAnalysesData AnalysisPrograms Output
Documentation Who,What,When
Security InformationAccess LackofAuditing
Concerns with Traditional Process
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How Can ACES Help?
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ACESisasecure,webbasedplatformtohelpclinicalteamsimplementfixedand
adaptivetrialdesignswithinterimanalyses
WorkflowAutomation
SecureFirewalls
DocumentStorage
Auditing Reporting GlobalAccess
CreateSecureFirewalls UniqueUsernamesand
Passwords
RoleBasedSecurity
MaintainsStudyBlind
DocumentandInformationStorage Centralized
ControlledAccess
Auditable
Protect Trial Integrity
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Security
Audit TrailDocument Storage
AutomatedAnalysis BlindedInterimAnalysis
RestrictAccesstoBlindedInformation LimitSponsorInvolvement
ControlAccesstoInformation CentralizedInformation
Portal
Reduce Operational Bias
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Security
Audit TrailDocument Storage
Information Portal
Automated Analysis
Information Portal
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Firewalls
Security
Audit TrailDocument Storage
Automated Analysis
Information Portal
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Firewalls
Information Portal
Unblinded Blinded
DMC and ISC Sponsor and Steering Committee
Sponsorexposuretounblindedinterimdata,throughtheDMCorotherwise,canpresentsubstantialrisktotheintegrityofthetrial.
UnblindedinterimdataandtheresultsofinterimanalysesshouldnotbeaccessiblebyanyoneotherthanDMCmembersorthestatistician(s)performingtheseanalysesandpresentingthemtotheDMC.
Sponsorsshouldestablishwrittenprocedures,whichmaybeincludedintheDMCcharter,toensuretheminimizationofbias,suchasmaintainingconfidentialityoftheinterimdata.
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Building Firewalls and Protecting Data
Source: FDA Guidance: Establishment and Operation of Clinical Trial Data Monitoring Committees, March 2006
ACESsatisfiestheserequirementsbyenforcingtherulesidentifiedintheDMCCharter,andbyprovidingunequivocal
evidenceofthatenforcement.
"Awelltrustedfirewallestablishedfortrialconductbeyondthoseestablishedfor
conventionalgroupsequentialtrials canhelpprovideassurancethatstatisticaland
operationalbiaseshavenotbeenintroduced."
FDADraftGuidanceonAdaptiveDesign(2010)
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Building Regulatory Trust
FDArecommendsthattheDMCorthegrouppreparingtheconfidentialinterimreportstotheDMCmaintainallmeetingrecordsinordertobestensurecontinuedconfidentialityofinterimdata.
FDAmayrequestcopiesoftheserecordswhenthestudyiscompleted.
FDAmayalsorequestaccesstotheelectronicdatasetsusedforeachsetofinterimanalysis.
FDArecommendsthatsponsorsarrangeforarchivingsuchelectronicdatasets.
ACESsatisfiestheserequirementsprovidingcapabilitiestoautomateinterimanalysisreporting,archiveinputdatasets
andoutputreports,andmaintainmeetingrecords.
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Automating Analysis and Reporting
Source: FDA Guidance: Establishment and Operation of Clinical Trial Data Monitoring Committees, March 2006
Auditing Accountability AutomaticSnapshots
Data Parameters Outputs Decisions
RealTimeProcessInspections
Consistency
Increase Regulatory Trust
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Security
Audit Trail
Document Storage
Information Portal
Automated Analysis
Interim Snapshots
Process Tracking(Workflow)
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ACES Process
CreateDocuments
(Protocol,SAP,DMCCharter)
Store/ArchiveDocuments
EnrollSubjects&Collect
Responses
SendResponseDatatoISC
PerformAnalysisand
CreateReports
SendAnalysistoDMC
Spo
nsor
ISC
DM
C MakeRecommendation
SendRecommendationtoSponsor/Steering
Committee
MakeDecisionaboutTrial
Ste
erin
gC
omm
ittee
in ACES
Afterdecision1.DMCnotified2.DrugSupplynotified3.IVRSnotified
in ACES in ACES
Create andTest
AnalysisPrograms
LoadFinalAnalysisPrograms
into ACES
Request additional information
with ACES
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ACES Demo
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Benefits of Using ACES
Access
Centralized WebBased InternalandExternalUsers
Centralized WebBased InternalandExternalUsers
Workflow
UserManagement TrialDesign InterimAnalysesPlanning
UserManagement TrialDesign InterimAnalysesPlanning
Consistency
AcrossStudies Process Communication
AcrossStudies Process Communication
Control
UserAuthentication Firewalls AccessRestrictions
UserAuthentication Firewalls AccessRestrictions
Documentation
TrialDocuments InterimAnalyses AuditedAccess
TrialDocuments InterimAnalyses AuditedAccess
Trust&Confidence
Transparency Evidence Reporting
Transparency Evidence Reporting
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StatisticsPackages SAS R
DocumentManagementSystems
System Integrations
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Security
Audit Trail
Document Storage
Information Portal
Automated Analysis
Interim Snapshots
Process Tracking(Workflow)
API
Document Management
Systems
R
SAS
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Future Extensions and Integrations
IVRS/IWRS
DrugSupply
EDCCTMS
SubjectData ResponseData
TrialData Investigator/SiteData PlannedMetrics
RandomizationData DynamicChange/Update
TreatmentProbabilities
WarehouseandSiteInventories
ResupplyThresholds
Design/Simulation
Algorithm ParameterData
DashboardsandAnalytics
SubjectEvents/Responses EnrollmentForecasting DrugSupplyForecasting SiteMonitoring
Optimization Portfolio
Management/NPV
UsingACESforexecutingtrialsandperforminginterimanalysesenables Isolationoftheunblindedtrialdatatoasecureenvironment Avoidsanyquestionofaffectingthetrialintegrity
Allinterimanalysesprocess,data,anddecisionsarecapturedforacompletetrialhistory
Guaranteesthatnochangesweremadetocriticaldocumentsafterdatawasunblinded StatisticalAnalysisPlan(SAP) DMCCharters ProtocolDocument
Generatesandsecurelystoresblindedorunblindedreportsforreviewbytargetedindividuals MoresecurethanemailorUPS/FedEx Unequivocalassurancethatkeyusers(ISC,DMC)haveopened
documents
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Actual and Potential Benefits
OperationalBias isgreatlyreducedbyusingsecuresystems,andbylimitingaccesstounblindeddata
TrialIntegrity isprotectedbydocumentingtheconduct,logistics,andoperationofthetrialthroughsecurityandaudittrails
RegulatoryConfidence intheconsistentexecutionofadaptivetrialsbyimplementingsystemsthatenforcebestpracticeprocesses
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Closing Remarks
SMi AdaptiveDesignsinClinicalDevelopmentLondon,March2627,2012
Ericspeaksonprotectingtrialintegrity,reducingoperationalbias,andbuildingregulatoryconfidencewhenconductinginterimanalyses
ICSAAppliedStatisticsSymposiumBoston,June2326,2012
Ericstalktitled,OptimizingHumanInteractionsandInformationFlowDuringInterimAnalyses
ASCO,Chicago,June15,2012CyrusMehta,CytelPresident
BIO,Boston,June1921,2012
DIA,Philadelphia,June2428,2012
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Learn More Meet Us
Exact times & places TBA: watch cytel.com
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Please Take the 5-minute Survey
Please complete the short survey that appears immediately upon webinar end.
Your opinions and interests will help guide our thinking toward shaping an agenda for future webinars.
Thank you.
FDADraftGuidanceonAdaptiveDesignClinicalTrials (source:www.fda.gov)
FDAGuidanceonDataMonitoringCommittees (source:www.fda.gov)
EMEAGuidelineonDataMonitoringCommittees (sourcewww.emea.europa.eu)
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Learn More - References
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Thank You for Joining Today
EricJ.Silva,Cytel,Inc.StevenKetchum,Ph.D.,SunesisPharmaceuticals
www.valortrial.com
