PROCESS CHART - Med...2018/05/18 · Risk and Contingency plan Understand Real Needs Clarify what...

Copyright：臨床研究の品質向上ツール作成WG＆日本医師会,2018Allrightsreserved

PROCESSCHART臨床研究の品質向上ツール作成WG

18/03/31 ProcessChart_臨床研究の品質向上ツール作成WG 1


本研究の⽬的• 現時点において品質管理システムあるいは品質管理計画に基づく、Goal志向のデザインアプローチとなるQualitybyDesign（QbD）において、プロトコルに必須の領域あるいは実臨床に関連する領域での品質管理指標として、何を基準にどのように推奨するかについて、まだ汎⽤的なツールがないのが現状である。• 本研究では、被験者保護、データの質確保を⽬標として、QbDによる実施計画書の作成に必要なツールを検討及び作成し臨床研究の品質向上を⽬指す。



本研究で整備⽬標としたQbDツール


QbD概念に対する教育コン

テンツ

QbDによるプロトコル開発

プロセスチャート

品質管理項⽬を組み込んだ実施計画書

フローチャート提⽰PPT提⽰

次期活動で検討（H30年度）


WholeProcessofQbDprotocolplanning


ClinicalQuestionDrugSeeds

ResearchQuestionTPP/CDP

SynopsisProjectCharter

Protocoldraft

QMplanPMplan

ProtocolRMP

SpecificationofClinicalQuestionResearchyourtopicStructureofPICO/PECOBrushupusingFINERmethod

MissionProfiling(TPP/CDP)SetupthegoaloftheStudyProtocolSynopsisConsiderationofProjectScope,Time,CostMakeProjectCharter

QualitymanagementplanSynopsisbrushupDraftcostestimationRiskmanagementandMitigationplanFinalizeProjectmanagementplan

ProtocolfeasibilityassessmentDetailscostestimationConstructionofdraftRMPFinalizationofProtocolFinalizationofRMP

InvestigateRQs ProjectDesign QualitybyDesign FeasibilityAssessment

ScientificOutcome

ManagementOutcome

*

*:TPP:TargetProductProfile,CDP:ClinicalDevelopmentPlan,QM:QualityManagement,PM:ProjectManagement,RMP:Risk-basedMonitoringPlan


INVESTIGATERQS








Protocoldraft

QMplanPMplan

ProtocolRMP







InvestigateResearchQuestions

SpecificationofClinicalQuestion

Researchyourtopic

StructureofPICO/PECO

BrushupusingFINERmethod

7

ClinicalQuestion

ResearchQuestion

Output

input

18/03/31 ProcessChart_臨床研究の品質向上ツール作成WG


SpecificationofClinicalQuestion


Input Process Output

ClinicalQuestion Wants/Needsspecification ResearchTopic

• clinicalquestionfrombedside

• Realunmetneeds• Clinicalwants• Stateoftheart• ClinicalGuideline• Casereport• EHRdata• Reputationsurvey

• Researchhypothesis• Thesaurus• Searchword


Researchyourtopic



ResearchTopic Literaturereview ClinicalQuestion(detail)

• Researchhypothesis• Thesaurus• Searchword

• Clinicalguideline• Pubmed• MEDLINE• CochraneDatabase/SystematicReview• Scopus• GoogleScholar• Criticalappraisalofselectedpapers

• Researchhypothesis(detail)• ClinicalQuestion(detail)


StructureofPICO/PECO



ClinicalQuestion(Detail)

SpecificationofPICO/PECO

ResearchQuestions(draft)

ConsiderStudyDesign

• Researchhypothesis(detail)• ClinicalQuestion(detail)• Compound

• PICO/PECOP(Patient)I(Intervention)/E(Exposure)C(Comparison)O(Objective)• StudyDesign(draft)

• ResearchQuestions(draft)• TrialGoal(draft)• Researchbenchmark

DrugSeeds


RQsbrushupusingFINERmethod



ResearchQuestions(draft)

ResearchQuestions(RQs)

EvaluateRQsbasedonFINER

• ResearchQuestions(draft)• TrialGoal(draft)• Researchbenchmark

• FINERevaluationF:FeasibleI:InterestN:NovelE:EthicalR:Relevant

• ResearchQuestionsTrialGoal(draft)• Researchbenchmark


PROJECTDESIGN








Protocoldraft

QMplanPMplan

ProtocolRMP







ProjectDesign

MissionProfiling（TPP/CDP）

SetupthegoaloftheStudy

ProtocolSynopsis

ConsiderationofProjectScope,Time,Cost

MakeProjectCharter

14

ResearchQuestion

SynopsisProjectChater

Output

input

18/03/31 ProcessChart_臨床研究の品質向上ツール作成WG


MissionProfiling



DrugSeeds

CompoundPatentHealthcareenvironmentHypothesisoftheStudyP:PatientI/E:Intervention/ExposureC:ComparisonO:Outcome

Efficacy/SafetybenchmarkDrugProductDosingRegimenPatentScientificInterestNoveltySocialImpactMedicalRealNeedsPositioninginthemedicalfieldCompetingproductResearchRegulatoryResearchMarketingResearchRiskassessmentDefineCriteriaforGo/Nogo

IdentifyTargetProductProfile

Environmentalfactor

ClinicalDevelopmentPlan（Draft）

ResearchQuestion（RQ）

MissionProfiling

TPPPositioningCompetingproductDevelopmentStrategyRegulatoryStrategyMarketingStrategyPatentInformationDecision-makingapproachRiskestimation


MissionProfiling(contd.)


Asis

Tobe

ResearchQuestionProjectValue

Intangiblevalue

Gapanalysis

CDP

Tangiblevalue

StudyGoal

FINER Relevant

NewTreatment


MissionProfiling 概念図


現状

実⾏シナリオ

課題①

課題②

課題③

プロジェクト①

プロジェクト②

プロジェクト③

現状を正しく理解する⽬指す状態

ギャップを理解し、プロジェクトを定義、シナリオを作り実⾏する

関係性分析課題の明確化プロジェクトの検討体制の検討

ミッション表現成果物の価値を表現シナリオ展開

実⾏性を検証しシナリオを作成

到達レベル

時間

開発シーズ医療ニーズ

新しい医療の提供

CDPTrialPlan

ThegoalofStudy

特許

安全性

薬事規制

TPPTrialProfile

プログラム


SetupthegoaloftheStudy



ClinicalDevelopmentPlan（Draft）Environmental

factorTPPFinancialplanResourceplanDevelopmentScheduleStudyplanThegoalofthestudyStudyDurationDefinitepositioningQualityPolicyRegulatoryStrategyMarketingStrategyPatentInformationDecision-makingapproachRiskandContingencyplan

UnderstandRealNeeds

Clarifywhattoverify

FeasibilityEthicalityMedicalRealNeedsStudyGoalQualityGoalPositioninginthemedicalfieldEstimatecostEstimateResourceEstimatescheduleWhattoverifyAppropriatePICO/PECO

TPPPositioningCompetingproductDevelopmentStrategyRegulatoryStrategyPatentInformationDecision-makingapproachRiskestimationFinancialrequirementsResourcerequirementsDevelopmentScheduleNumberofPatient

Setupthegoalofstudy

EstimateCost,Resource,Schedule

ClinicalDevelopmentPlan


TargetProductProfile（TPP）•  TPP:承認申請に必要な開発プログラム全体の意図が記載され、その時点での適切な情報が記載されているもの。開発のゴールが明記されている。(2007年3⽉FDAガイダンス）

•  TPPに記載すべき項⽬（例）•  製品の概要•  疾患セグメント•  Keyとなる項⽬•  有効性：有効性のベンチマーク、Go/Nogoの判断基準•  安全性：安全性のベンチマーク、Go/Nogoの判断基準•  製剤：規格・安定性や扱いやすさ（保管条件）•  投与計画：経路・⽤法⽤量



ClinicalDevelopmentPlan（CDP）• 臨床開発計画（ClinicalDevelopmentPlan、CDP）•  どのようなターゲットに対して、どういう試験を実施するかにつ

いてまとめたもの

• CDPの項⽬の例•  開発の経緯•  薬効・薬理の概略•  臨床的な位置づけ•  類薬の開発状況•  ⽤量探索・有効性及び安全性評価計画（I相〜III相、⻑期試験等）•  リスクとその対応策•  ⼈員、資⾦計画•  タイムスケジュール•  意思決定⽅法



ProtocolSynopsis



ThegoaloftheStudy

ConsidertheStudyDesign

ProtocolSynopsis

Determinethestudysubject

StudyrealObjectiveStudyDurationAppropriatePICO/PECOP:PatientI/E:Intervention/ExposureC:ComparisonO:OutcomeDefinitepositioningWhattoverifyQualityPolicy

StudyObjectiveTargetSubjectInclusionCriteriaExclusionCriteriaStudyDesignEndpointComparativeControlledTherapyTargetnumberofsubjectsStatisticalAnalysis

QualitygoalTargetSubjectCriteriaNumberofSubjectComparisonEndpointAnalyticalmethodofendpointStudyMethodInvestigationItem

DetermineQualitygoal

Designthenumberofsubject

ObjectifyRQClarifyRQ

ClinicalDevelopmentPlan


ConsiderationofProjectScope,Time,Cost



ProtocolSynopsis

EstimatetheprojectSchedule

Estimatetheprojectcost

DefinitetheQualitygoal

StudyObjectiveStudySubjectInclusionCriteriaExclusionCriteriaStudyDesignEndpointComparativeControlledTherapyTargetnumberofsubjectsStatisticalAnalysisPastCasesOrganizationalKnowledge

StudyScheduleRequisiteDurationtoconductstudyRequisiteQualitygoalRequisitecostRequisiteResourceRegulatoryRequirement

EstimateResource

ProjectCharter

（Draft）

ProjectObjectiveQualitygoalProjectDurationProjectCostDeliverableStudyOrganizationStudyMethod

DeterminetheDeliverable

Referpastcases

OrganizationalKnowledge


MakeProjectCharter



ProjectCharter

（Draft）DecidePriorityofProject

Scope,Time,Cost ProjectCharter

AssesstheProjectRisk

IdentifytheStakeholder

ProjectObjectiveQualitygoalProjectDurationProjectCostDeliverableStudyOrganizationStudyMethodSummaryofStudy

ProjectObjectiveProjectGoalProjectRiskMilestoneScheduleBudgetaryEstimateStakeholderProjectExitcriteriaProjectsuccesscriteriaProjectDurationAssumptionConstraintProjectRequirement（Scope）

Priority（Quality（Scope）,Time,Cost）ProjectRiskRegulatoryRequirementOrganizationalneedsCustomerRequestQualitygoalProjectmemberProjectResource

AssesstheStudycircumstance


QUALITYBYDESIGN








Protocoldraft

QMplanPMplan

ProtocolRMP







QualitybyDesign

Qualitymanagementplan

Synopsisbrushup

Draftcostestimation

RiskmanagementandMitigationplan

FinalizeProjectmanagementplan

ProcessChart_臨床研究の品質向上ツール作成WG 26

SynopsisProjectChater

ProtocoldraftQMplanPMplan

input

Output

18/03/31


Qualitymanagementplan



ProjectCharterIdentifytheProjectRisk

QualityManagementPlan

Definethequalitypolicies,measurements

ProjectObjectiveProjectGoalProjectRiskMilestoneScheduleBudgetaryEstimateStakeholderProjectExitcriteriaProjectsuccesscriteriaProjectDurationAssumptionConstraintProjectRequirement

1.Qualitypolicyofthetrial2.Requirementsofthetrial(customer,lawsandregulations,implementationsystem)3.Scopeandauthority4.Riskidentificationandriskmanagementplan5.Qualitymanagementplan6.Qualitymanagement(monitoringmethods,monitoringmethods)7.Qualityassurance(thepresenceorabsenceofaudit,systemoftheaudit)8.Changemanagement9.Educationandtraining

ClarifythegoaloftheclinicaltrialDefinethequalitypolicyDefinethequalityobjectivesRiskassessment

ProtocolSynopsis


QualityManagementPlanp Clarifythegoaloftheclinicaltrialp Definethequalitypolicyp Definethequalityobjectivesp Riskassessment


TrialProtocol

SOPs,WorkingInstruction

manuals

Preparationforthequalitymanagementplan

Preparationfortheoperatingprocedureorinstructionsfortrial

monitoringandauditing

Planningtheprotocolwell-behavedfromthequalitymanagementplan

•  QualityManagementSystem(SOPs,Computerizedsystems,humanresources,outsourcing,infrastructure)

•  Clinicaltrialprotocol (investigationalnewdrugs,trialdesign,datacollectingprocess,monitoringprocess,documentsorrecords）



Synopsisbrushup



ProtocolSynopsis Protocoldraft

StudyObjectiveTargetSubjectInclusionCriteriaExclusionCriteriaStudyDesignEndpointComparativeControlledTherapyTargetnumberofsubjectsStatisticalAnalysisIndicationStudyDurationQualityrequirementTrialtimeline

QualitygoalTargetSubjectCriteriaNumberofSubjectComparisonEndpointAnalyticalmethodofendpointStudyMethodInvestigationItem

StudyObjectiveTargetSubjectInclusionCriteriaExclusionCriteriaStudyDesignEndpointComparativeControlledTherapyTargetnumberofsubjectsStatisticalAnalysis

ConsidertheQMP

Determinethestudyoutcome

DetermineTrialTimeline

ConsiderthepolicyofRiskManagement


Draftcostestimation



ProtocolDraft ConsiderProtocoldraft

ProjectCostPlan



Considerprotocoldraft,includingtimeline,outcomes,qualitygoals,duration,studyresourceCostestimationQualityrequirements

Estimatetheprojectcost

EstimateResource

DeterminetheDeliverable

Referpastcases

ProjectCharter


RiskManagementandMitigationplan



QualityManagementPlan ConsiderRiskand

AssessmentRiskManagementandMitigationPlan

ConsiderCAPAplan

ConsiderRiskMitigationPlan

1.  RiskManagement2.  RiskQuantitative

Analysis3.  RiskQualitative

Analysis4.  RiskMitigation

plan5.  RiskControl6.  CAPAplan

ConsiderRiskManagementplanIdentifyRiskRiskanalysis:QuantitativeandQualitativeanalysisConsiderRiskMitigationandRiskControlConsiderCAPAplan

1.Qualitypolicyofthetrial2.Requirementsofthetrial(customer,lawsandregulations,implementationsystem)3.Scopeandauthority4.Riskidentificationandriskmanagementplan5.Qualitymanagementplan6.Qualitymanagement(monitoringmethods,monitoringmethods)7.Qualityassurance(thepresenceorabsenceofaudit,systemoftheaudit)8.Changemanagement9.Educationandtraining


FinalizeProjectmanagementplan



RiskManagementandMitigationPlan

DefineProjectActivity

ProjectManagementPlan

ConsiderRiskManagement

plan

Considerresource,cost,

duration,stakeholders


1.ScopeManagement2.ProjectRequirements3.ScheduleManagement4.CostManagement5.QualityManagement6.ResourceManagement7.CommunicationManagement8.RiskManagement9.ProcureManagement10.StakeholderEngagement11.ChangeManagement12.ConfigurationManagement13.Scopebaseline14.Schedulebaseline15.Costbaseline16.Performancebaseline17.ProjectLifecycle18.DevelopmentMethod

CorrectiveandPreventiveActionConsiderQualityManagementplanDefineprojectactivityandscopeDefineprojectdevelopmentandchangemanagementmethodConsiderRiskManagementplanConsiderProtocolDraft

ProjectCostPlan



FEASIBILITYASSESSMENT








Protocoldraft

QMplanPMplan

ProtocolRMP







FeasibilityAssessment

Protocolfeasibilityassessment

Detailscostestimation

ConstructionofdraftRMP

FinalizationofProtocol

FinalizationofRMPProtocolRMP

ProtocoldraftQMplanPMplan

input

Output



Protocolfeasibilityassessment



Protocoldraft Reviewprotocoldraft

Protocolfinaldraft

IdentifycandidatesitesPMplan

QMplanDesignPatientpopulationIndicationI/EcriteriaSamplesizeEndpointsDurationQualityrequirementTrialtimeline

KeyRoleIntroductionObjectiveStudyDesign,EndpointsEnrollmentInvestigationaldrugStudyProcedureStudyScheduleAssessmentofSafetyClinicalMonitoringStatisticalConsiderationsSDV,SourceDataEthicsDataHandlingStudyadministrationCOI,Publication

EnsureclinicalfeasibilityEnsurescientificfeasibilityEnsureethicalfeasibilityEnsureoperationalfeasibilityEnsureregulatoryfeasibilityEnsurelegalfeasibilityDiscusswithPIs,Regulatory

DiscusswithPIs,regulatory

Identifydifficulty


Detailscostestimation



Protocolfinaldraft

Sharewithvendors

Finalcostestimation

Obtainestimatefromvendors

PMplanQMplanDesignTimelineSamplesizeTrialorganizationRegulatoryrequirementProtocolrequirementQualityrequirementCriticaltoQuality(CTQ)Riskmitigationplan

Discussaboutresource(people,materials,cost)ShareprotocolwithvendorsCollectallcostestimationsEstimatedirect,passthrough,fixesandvariablecost

Estimateperpatientcost

Estimatedirectcost

DirectcostPassthroughcostFixescostVariablecostSitecostVendor(EDC/CRF,IXRS,Centrallab,CRO,SMO,Medicalwriting,DM/Stat,Audit)cost



ConstructionofdraftRMP



Protocolfinaldraft

Discussmonitoringplan

DiscussPMplan

PMplanQMplanEndpointsCandidatepatientsBudgetestimateTrialcostTrialorganizationTrialcomplexityPotentialriskFixedtimelineQualityrequirements

AcceptableprotocolfinaldraftMonitoringtypeMonitoringfrequencyMonitoringteamKeyriskindicatorsRiskmitigationplanDraftauditplan

ConfirmacceptanceofproceduresDiscusskeyriskindicatorsDiscussqualityrequirementsDecidemonitoringtype(central,onsite)DecidemonitoringfrequencyUpdateprotocoldraftPreparemonitoringplan

Risk-based MonitoringPlan(draft)DiscussQM

plan

Updateprotocolfinal

draft



FinalizationofProtocol



Finalcostestimation

Finalizeprotocol Fullprotocol

DesignPatientpopulationIndicationI/EcriteriaSamplesizeEndpointsAnalysismethodsTrialtimelineTrialcostTrialorganizationTrialcomplexityTrialdifficultyPotentialriskMonitoringplan

FixedfullinformationforprotocolFixedtrialcostCRFindex

InputfeasibilityresultintodraftprotocolRe-confirmvoiceofcustomerRe-confirmcustomerrequirementsDiscussoutputdata(Table,Figure,Listetc)UpdatedraftprotocolProtocolreviewbyteamProtocolreviewbyexpert

DraftRMP


FinalizationofRMP



FinalProtocol Discussmonitoringplan

PMplanQMplanEndpointsAnalysismethodsTrialtimelineTrialorganizationTrialcomplexityMonitoringtypeMonitoringfrequencyMonitoringteamKeyriskindicatorsRiskmitigationplanDraftauditplan

AcceptablefinalmonitoringplanMonitoringtypeMonitoringfrequencyMonitoringteamKeyriskindicatorsRiskmitigationplanAuditplan

ConfirmacceptanceofproceduresDiscusskeyriskindicatorsDiscussqualityrequirementsDecidemonitoringtype(central,onsite)DecidemonitoringfrequencyUpdateprotocoldraftPreparemonitoringplan

Risk-based MonitoringPlan(Final)DraftRMP

PROCESS CHART - Med...2018/05/18 · Risk and Contingency plan Understand Real Needs Clarify what...

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