getting multi-site trials up and running on time

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, MBAFrankie Kropp, MS

November 20, 2013

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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.

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Resource Collaborators for Trial Implementation

Node/ RRTC

CCC

DSCCCTN

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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

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CRITICAL COMPONENTS OF MULTI-SITE TRIALS

DevelopmentProtocol Approval

Trial Dev’t and LogisticsData ManagementNational Training

Study Start

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

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Timeline from Development to Study Start

Dev’t ProtocolApproval

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 assignedInitial Budget/revise as neededTimeline Development

Protocol Reviews: PRB, DSMB, Lead Node IRB ApprovalSite SelectionOther Regulatory Submission(s)

Revise eCRFs at DM meetingThen, revise Ops Manual as needed (recruitment materials, logs et. al.) Selected Sites Hiring Staff

Initiation Visits (Node QA/CCC)Site EndorsementsStart Enrollment

Training Doc FormDelegation LogRegulatory Training/Document CollectionSupplies/Meds to sites

Other Study Docs in Dev’t: eCRFs, Ops Manual, QA Plan, SOPsTraining Dev & PlanningMeds, Labs, and Supplies ContractsSites to submit for IRB Approval

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PREPARATION ACTIVITIES AND REQUIREMENTS

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TEMPLATE AVAILABLE ON THE CTN INVESTIGATOR TOOLBOX AT WWW.CTNDSC2.COM/

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DevelopmentNode/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

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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

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Protocol ApprovalNode/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

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TEMPLATE AVAILABLE ON THE CTN INVESTIGATOR TOOLBOX AT WWW.CTNDSC2.COM/

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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

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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

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TEMPLATE AVAILABLE ON THE CTN INVESTIGATOR TOOLBOX AT WWW.CTNDSC2.COM/

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Break for Questions

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

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TRIAL DEVELOPMENT AND LOGISTICS

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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

Node/RRTC

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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

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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

Node/RRTC

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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

CCC DSC

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National TrainingNODE/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

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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

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STUDY START-UP

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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

NODE/RRTC

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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

CCC DSC

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Study Startup…

…success achieved when all sites are enrolling.

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OVERCOME CHALLENGES

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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

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Tools• Use the tools available

– Timeline Template– Study Budget– Pre-Implementation Calculator

TEMPLATES AVAILABLE ON THE CTN INVESTIGATOR TOOLBOX

AT WWW.CTNDSC2.COM/

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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

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Q&A – Questions / Comments

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

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Survey Reminder

Upcoming Webinar

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SECONDARY ANALYSES FOR CLINICAL TRIALS IN DEVELOPMENT***Note the Date Change***Friday, December 6, 201312:00 pm to 1:30 pm ET

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A copy of this presentation will be available electronically after this session.

http://ctndisseminationlibrary.org

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Thank you for participating.NIDA CTN Web Seminar Series