1. 2013 CTN Web Seminar Series Produced by: NIDA CTN CCC Training Office "This training has been funded in whole or in part with Federal funds from the National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, under Contract No.HHSN271201000024C." GETTING MULTI-SITE TRIALS UP AND RUNNING ON TIME Presented by: Colleen Allen, MPH Eve Jelstrom, CRNA, MBA Frankie Kropp, MS November 20, 2013

2. Objectives Identify critical components of multi-site trials for effective implementation. Explain preparation activities and requirements from stakeholders for site endorsement. Consider methods to overcome challenges. 2

3. Resource Collaborators for Trial Implementation 3

4. Resource Collaborators for Trial Implementation (continued) Composition of the Lead Team –CCTN –Node/RRTC –DSC –CCC All in the CTN engage in research; this presentation will focus on the efforts of the Node/RRTC, the Clinical Coordinating Center, and the Data & Statistics Center 4

5. CRITICAL COMPONENTS OF MULTI-SITE TRIALS 5

6. Pre-Implementation Milestones Development Protocol Approval Trial Development and Logistics Data Management Meeting National Training Study Start 6

7. 7 Timeline from Development to Study Start Dev’t Protocol Approval Nat’l Training DM Meeting Study Start Trial Dev & Logist. 6-8 wks before nat’l trng 4 wks before study start CCTN Concept Approval CTN Number assigned Initial Budget/revise as needed Timeline Development Protocol Reviews: PRB, DSMB, Lead Node IRB Approval Site Selection Other Regulatory Submission(s) Revise eCRFs at DM meeting Then, revise Ops Manual as needed (recruitment materials, logs et. al.) Selected Sites Hiring Staff Initiation Visits (Node QA/CCC) Site Endorsements Start Enrollment Training Doc Form Delegation Log Regulatory Training/Document Collection Supplies/Meds to sites Other Study Docs in Dev’t: eCRFs, Ops Manual, QA Plan, SOPs Training Dev & Planning Meds, Labs, and Supplies Contracts Sites to submit for IRB Approval

8. PREPARATION ACTIVITIES AND REQUIREMENTS 8

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10. Development Node/RRTC Protocol development and improvement Budget development Protocol Concept Submission Cost-benefit ratio for each study procedure Expected rate of recruitment for target N Number of sites required to reach target N Impact of inclusion/exclusion criteria on recruitment Potential safety issues and how they will be managed 10

11. Development (continued) CCC Discuss division of responsibilities Consult Lead Team to clarify elements of the study Investigate study needs – medication, packaging, laboratory assessments or other study needs – important for budgeting and cost allocation Collaborate on timeline development DSC Evaluate required assessments and data reporting and collection Tie assessments and data collection to endpoints, protocol adherence and safety monitoring Define requirements and specifications for CRFs Use standard forms to streamline and expedite database development 11

12. Protocol Approval Node/RRTC Update study budget throughout the approval process Once approved, begin initial work on the Ops Manual, the Trial Performance Mgmt/QA plan, Training Plan, Source Doc development, etc. With CCC and NIDA identify any additional regulatory requirements that exist and with CCC complete submissions Determine # of staff hours for each procedure Determine supplies and training for personnel Determine costs for travel, specialty training, etc. Additional documents may include OHRP – Prisoner Certification or IND (Investigational New Drug) application or exemption 12

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14. Protocol Approval (continued) Node/RRTC Determine and document site selection process Present selected sites for Executive Committee/NIDA approval Inform sites once approved Site criteria should be clearly established. Decide targeted sites vs. open call Develop site survey documents and track results Determine and present budget parameters, and once informed, finalize site- specific study budgets 14

15. Protocol Approval (continued) CCC Processes – identifying, recruiting, consenting, screening participants – assessments, and medication management and tracking Develop more detailed timeline and chart responsibilities Discuss and help develop plans for site needs and resource management Discuss management plans for particular study – training, risk, monitoring Confirm study specific regulatory requirements DSC Begin development and programming of CRFs Share drafts of CRFs with the team for review and input Consider planned study workflow: – How performance of required assessments and data collection/reporting will work into study operations 15

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17. Break for Questions 17 Alternatively, questions can be directed to the presenter by sending an email to CTNtraining@emmes.com.

18. TRIAL DEVELOPMENT AND LOGISTICS 18

19. Trial Development and Logistics Coordinate with CCC and DSC to complete – Final drafts of study documents and management tools – Final training plan and documentation – Approval of submitted regulatory materials – Pre-initiation checklist and teleconferences Study documents including the Ops Manual and TPM/QA plans Tools including Study logs and checklists, Progress notes Provides approved submission materials to sites and posts on LiveLink 19 Node/RRTC

20. Trial Development and Logistics (continued) CCC Collaborate to finalize study medication, documents, and management tools Finalize laboratory, consultant, and vendor contracts Finalize Delegation of Authority and Staff Signature Log On calls review Pre-Initiation checklists addressing Lead Node, CCC and DSC key items Collect protocol wide Regulatory Documents DSC Complete and review drafts of all CRFs prior to data management meeting Plan for data management meeting to be held 6-8 weeks prior to National Training Meeting Develop AdvantageEDC User’s Guide and CRF Manual, GlobalTrace User’s Guide and AdvantageEDC Practicum 20

21. Data Management Meeting Lead Node works with CCC and DSC to finalize eCRFs and database Finalize study guidance documents and tools Training plan and documentation form to sites Lead Node monitors site progress towards initiation weekly 21 Node/RRTC

22. Data Management Meeting (continued) Integrate Ops Manual with Protocol with CRFs Identify source documents Finalize all study guidance docs and management tools Finalize training plans and Investigator Meeting agenda 2 day meeting held 6-8 weeks prior to National Training Meeting Critically review CRFs Identify all changes to CRFs; required to meet timeline for database completion prior to protocol training Trial progress and data status reports planning – LN should provide specifications for reports to the DSC by the time of the National Training 22 CCCDSC

23. National Training NODE/RRTC Lead Node coordinates with CCC and DSC to complete all training events Lead Node tracks completion of training requirements for all site and node personnel Lead Node continues monitoring site progress towards initiation weekly 23

24. National Training (continued) CCC Plan for Training 3-4 months prior to training. Finalize Training Documentation Form for use by sites and approval by Lead Node. Decide if Training to occur in person or remotely in consultation with CCTN. Develop agenda and timing for on-site and webinar training sessions. DSC Final study database to be available at the time of the National Training Meeting Plan to provide training on AdvantageEDC, GlobalTrace, and Good Data Management Practices Complete development of the AdvantageEDC User’s Guide and CRF Manual, GlobalTrace User’s Guide, and Practicum Issue and grade AdvantageEDC practicum shortly after the training Begin to develop Integrity queries Begin to develop trial progress/data status reports 24

25. STUDY START-UP 25

26. Study Start-up Lead Node coordinates with CCC to monitor results of site initiation visits and resolution of outstanding items Lead Node transitions pre-initiation teleconferences to study management teleconferences 26 NODE/RRTC

27. Study-Start Up (continued) Initiation visits by QA/Node staff and CCC Initiation reports issued Action Items resolved Endorsement of each site Screening and recruitment begins Begin to monitor data quality as soon as first participant is enrolled/randomized – Missing forms – Missing values – Integrity queries Begin to generate trial progress and data status report as soon as first participant is enrolled/randomized 27 CCC DSC

28. Study Startup… 28

29. OVERCOME CHALLENGES 29

30. Challenges Unforeseen regulatory compliance issues Keeping up with the timetable Lack of effective communication Sites and staff new to CTN research trials Site may need to drop out of the study after site selection 30

31. Tools 31 Use the tools available –Timeline Template –Study Budget –Pre-Implementation Calculator

32. Recap / Highlights Begin conversations about details early Consider the costs Determine what type of Lead Node you want to be Communicate, communicate, communicate Don't reinvent the wheel Reach out to existing resources 32

33. Q&A – Questions / Comments 33 Alternatively, questions can be directed to the presenter by sending an email to CTNtraining@emmes.com.

34. Survey Reminder Upcoming Webinar The NIDA CCC encourages all to complete the survey issued to participants directly following this webinar session, as this is the primary collective tool for rating your experience with this and other webinars, and for communicating the interests and needs of CTN members and associates. 34 SECONDARY ANALYSES FOR CLINICAL TRIALS IN DEVELOPMENT ***Note the Date Change*** Friday, December 6, 2013 12:00 pm to 1:30 pm ET SECONDARY ANALYSES FOR CLINICAL TRIALS IN DEVELOPMENT ***Note the Date Change*** Friday, December 6, 2013 12:00 pm to 1:30 pm ET

35. A copy of this presentation will be available electronically after this session. http://ctndisseminationlibrary.org 35

36. Thank you for participating. NIDA CTN Web Seminar Series 36