Welcome : New Resources for Designing & Running - PowerPoint Presentation

1. Welcome: New Resources for Designing & Running Master ProtocolsThis webinar is being recorded and will be posted to the CTTI websiteAll participants are muted upon entryQuestions can be entered in the chat box during the webinar There will be a “Question & Answer” session at the end of the webinar

2. New Resources for Designing & Running Master ProtocolsLeanne Madre, CTTINicholas Richardson, FDA, CDERDaniel Millar, Janssen R&DAbby Bronson, Edgewise TherapeuticsMarianne Chase, Massachusetts General HospitalOctober 13, 2020

3. DisclaimerThe views and opinions expressed in this presentation are those of the individual presenter and do not necessarily reflect the views of the Clinical Trials Transformation Initiative.

4. Welcome Leanne Madre, CTTI

5. AgendaCTTI Overview Emerging Best Practices & ResourcesIdentifying key deliverables and problem-solving approachesDemonstrating the value of patient-centered design innovationDriving alignment and consensus across key stakeholder groupsQ&A

6. Multi-stakeholder,public-private partnershipco-founded by Duke University & FDA Participation of 500+ more orgs and + 80 member organizationsMISSION: To develop and drive adoption of practices that will increase the quality and efficiency of clinical trials

7. VeloCTTI Project Methodology

8. Project Team Team LeadsTeam MembersDaniel Millar (Janssen R&D)Marianne Chase (Massachusetts General Hospital)Nicholas Richardson (FDA)Shenghui Tang (FDA)Sabrina Paganoni (Massachusetts General Hospital)Jane Perlmutter (Patient Advocate)Dionne Price (FDA)Paulina Selaru (Pfizer)Paul Bycott (Pfizer)Antonio Valkas (EMD Serono)Kert Viele (Berry Consultants)Karen Dimick (Genetech)Greg Licholai (Yale)Sharon Love (UCL)Sumithra Mandrekar (Mayo)Debra Michaels (DIA)Nicholas Kenny (Syneos)Barbara LeStage (Patient Advocate)Roger Lewis (UCLA, Berry ConsultantsAbby Bronson (Edgewise Therapeutics)Michelle Detry (Berry Consultants)Angie Botto-van Bemden (Patient Advocate)Gene Vinson (Syneos)Alain Vuong (GSK)Kirsty Wydenbach (MHRA)Louis Brown (UCL)Amy Burd (LLS)Emma Healy (Novartis)Ritesh Jain (EMD Serono)CTT StaffKim Fisher (Project Manager)Laura Shannon (Communications Manager)

9. Project OverviewNicholas Richardson, CDER, FDA

10. PurposeProvide diverse stakeholders with a roadmap for the successful design and implementation of master protocols

11. ObjectivesCompare and contrast the distinct design and operational features of basket, umbrella, and platform studies.Identify emerging best practices for the design and conduct of master protocol studies.

12. Goals of CTTI’s Master Protocol ProjectDemystify the ProcessProvide Educational ProgramsCreate Forums for DiscussionDrive Knowledge SharingStrengthen the Landscape

13. Tool Development ProcessIdentify Potential STRATEGIESPriortiize ROADBLOCKSDevelopTOOLS

14. Challenges and Problem-Solving ApproachesPre-PlanningPlanningExecution

15. Identifying Key Deliverables & Problem-Solving Approaches: High-Level Roadmap, Value Proposition Guide

16. MULTI-STAKEHOLDER ENGAGEMENTRationalePre-PlanningDESIGNFeasibilityProve valueOPERATIONS

17. MULTI-STAKEHOLDER ENGAGEMENTReach consensusPlanningDESIGNIntegrate, centralize processesEducationOPERATIONS

18. Fidelity,changeExecutionDESIGNCentralization,flexibility,communicationCultivate,maintainOPERATIONSMULTI-STAKEHOLDER ENGAGEMENT

19. New CTTI Master Protocol ResourcesStudy StageToolsPre-PlanningHigh-Level Roadmap: Describes key deliverables and problem-solving approaches critical to differentValue Proposition Guide: Outlines design & operational considerations to demonstrate the value of adopting a master protocol approachFDA Engagement Tool: Describes formal mechanisms to facilitate early engagement with the FDAMaster Protocol Reference & Resources: summary of key referencesPlanningMaster Protocol Content Development Guide: Describes key stakeholders and consensus-building deliverables that are required to build the content of master protocol studiesOperational Partner Assessment Tool: Summarizes factors that should be used to assess operational partners that may be useful to operationalize a master protocol designStatistical Simulation Tool: Lists core simulation modules and tips for how to best communicate findings of simulationsStudy ExecutionStudy Execution Case Studies

20. Value Proposition Guide: Demonstrating the Value of Patient-Centered Design InnovationDaniel Millar, Janssen R&D

21. Value Proposition Guide OverviewCommon challenge addressed:Early adopters — patient advocacy groups and other non-traditional trial sponsors —sometimes struggle to clearly and efficiently articulate the value and feasibility of developing a master protocol study in their disease area of choicePurpose:Identify considerations that can support early adopters’ efforts to think through the “why” and “how” of developing a master protocol studySupport early adopter’s ability to draft content for pitch decks, business plans, and other communications tools to engage stakeholders

22. Components of ValuePatientBenefitPatient-Centered Design InnovationOperational Feasibility Study GovernanceFundingArticulate the Value Proposition

23. Key Success FactorsDESIGNDemonstrate that the use of a master protocol study design increases patients’ access to innovative investigational products and reduces patient burden.OPERATIONAL CAPACITYDescribe how a centralized operational infrastructure will be built to facilitate the implementation of an innovative master protocol study designGOVERNANCEDescribe the governance structure that will facilitate efficient, centralized decision makingFUNDINGDescribe the resources that are required to cover the significant upfront planning costs of a master protocol study and ensure the long-term sustainability of the study

24. Demonstrating Value: Duchenne Adaptive Platform Trial Abby Bronson, Edgewise Therapeutics

25. Driving Value for the Duchenne CommunityThe clinical trial system for Duchenne muscular dystrophy has become incredibly slow and expensive.Multiple siloed trials all competing for the same patients slows all trials – and the redundancy of control groups can increase time and cost.Meanwhile, this global structure does not serve the Duchenne patients – and wastes their most precious resource: time.

26. Adaptive Platform Trial for Duchenne Muscular Dystrophy (APT-DMD)Phase 2, Phase 3, Phase 2/3 and post-approval trialsAge > 4Standard suite of endpointsInterim analyses and safety monitoring across platform and within armsEfficiencies gained from pooling placebo data across arms

27. Parent Project Muscular Dystrophy (PPMD) drug development forum, community engagement, Critical Path Institute (C-Path) Duchenne Regulatory Science ConsortiumBerry Consultants: Design, statistics, analysis planningI-ACT for Children: Master Protocol, Roadmap, Consortium DevelopmentIt Takes a Village

28. Demonstrating Value: Duchenne Platform Trial PATIENT-CENTERED DESIGN INNOVATION Multiple (local) trial sites increase patients’ opportunity to participate and lessens travel burdenPotential for better therapies to reach patients more quickly Less exposure to control groupBroader eligibility criteriaOPERATIONAL FEASIBILITY Potential for faster start-up:Sites already selected, qualified and trainedContracts in place, other operational efficienciesMaster protocol complete; FDA reviewedCRO will provide site training, monitoring, data collection, statistical analyses, regulatory supportSTUDY GOVERNANCEThe DPT Consortium is developing the Duchene Platform Trial, developing the business plan and operation plans for trial implementationFUNDINGFunding for trial planning comes from consortium members, including advocacy groups and drug sponsors

29. Protocol Development Guide & Operational Partner Assessment Tool: Driving alignment and consensus across key stakeholder groupsMarianne Chase, Massachusetts General Hospital

30. Protocol Development Guide OverviewCommon challenges addressed: Driving consensus on key design and operational features of the master protocol study across multiple stakeholdersIdentifying key stakeholders who should be actively engaged early in the planning stages of study development to guide the development of the written protocolDescription:Describes key consensus-building deliverables that need to be achieved in the pre-planning and planning stages of study developmentProvides a list of stakeholders that should be engaged in developing the content of the written master protocol and sub-protocols

31. Key Consensus-Building Deliverables

32. Achieving Consensus Across Multiple StakeholdersPatientsIMP DevelopersRegulatorsSafety ExpertsClinical OperationsData ManagementMedical WriterClinical Scientists

33. Unique Aspects of Consensus BuildingReaching consensus takes more time and resourcesMore stakeholders are required to participate in protocol content development earlier in the processConsensus building deliverables are not linear; they are iterative and cyclical across the life of a master protocol studyEfficiency is gained over time through preserving content of the master protocol document and allowing for flexibility in sub-protocolsMaintaining the content of the master protocol document should be a guiding principal of the consensus building process

34. Protocol Development Process is Integral to Operational Partner Network DevelopmentProtocol Developmentr NetworkPROTOCAL DEVELOPEMENTOPERATIONAL PARTNER NETWORK DEVELOPMENT

35. Operational Partner Assessment Tool Overview PatientsSafety ManagementEDC & Data ManagementCentralLabKey Descriptive ElementsUnique aspects of operational partners’ roleKey assessment factorsTraining and capacity building needsCROSite MonitoringSingle IRB

36. What makes operational partner selection unique in master protocol studies?Master protocol studies iteratively cycle across pre-planning, planning, and execution stages of study development asOperational partners will require training and education on the operational implications of the innovative design features of master protocol studies.Variability in workflow and budgeting will require operational partner to nimbly scale-up and scale-down their services to adjust to changing needs within the studyStandard business practices may need to adjust to better respond to the complex, changing needsFlexibility will be required to handle what may be a greater volume of work overall

37. Operational Partner Selection & Protocol Development: HEALEY ALS Platform Trial Examples

38. HEALEY ALS Platform Trial: Leveraging Innovative Trial Design to Accelerate Drug Development in ALSPatientsIndustry PartnersSitesFoundationsFDA

39. Operational Partner Selection: HEALEY ALS TrialUnique Challenge: Selection and contracting process with central labs commenced before the selection of IMPs. Identification of sample type, storage requirements, and processing turnaround time was ongoing at the time of operations partner selectionSuccess FactorsEnsure that the central lab and specialty labs understand that the scope and complexity of the work will evolve over time as new IMPs are added to the studyDevelop an approach to contracting to address data sharing and privacy concerns between the central lab, specialty lab, and industry partnersAnticipate and prepare to address challenges related to staff turnover.

40. Protocol & Sub-Protocol Content: HEALEY ALS TrialMaster ProtocolTarget patient populationSchedule of ActivitiesPrimary and secondary endpointsSample sizeTreatment durationKeep Master Protocol broad, to accommodate future IMPs without needing to amend the document!Appendix/Sub-ProtocolsRationale for testing investigational product (IP) in the defined patient populationAdditional inclusion/exclusion criteria – based on safety profileDetails about the investigational productAdditional assessments and/or biomarkers to be collectedAdditional secondary endpointsModifications should be based on safety requirements

41. Protocol Content Cross-Functional Review: HEALEY ALS TrialExecutive Leadership TeamIdentify and prioritize issues that should be addressed by specific functional groupsConfirm IMP selection Design & Operation MeetingsAddress issues prioritized by executive teamDiscuss operational implications of design elementsIdentify topics that require regulatory inputIndividual IMP MeetingsDetail review of the master protocol with individual IMP developerIdentify any necessary modifications requiredDevelop IMP-specific sub-protocol

42. Question & AnswerLeanne Madre, CTTI

43. Closing CommentsLeanne Madre, CTTI

44. Future Work Related to Master Protocol StudiesOngoing work to support early adopters who are in the early planning stages of a master protocol studyWorkshops to connect early adopters with experts who have substantial experience in the design and implementation of master protocol studiesCOVID-19 Master Protocol Public Webinar 2021

45. CTTI Mater Protocol Resources Links FDA Engagement ToolHigh-Level RoadmapMaster Protocol Content Development GuideMaster Protocol References & Resources Operational Partner Assessment ToolStatistical Simulation ToolStudy Execution Case StudiesALCHEMISTSTAMPEDEValue Proposition Guide

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