CURR0104 Flashcards
RACI
Responsible Accountable Consulted Informed
CRA Roles/Resposibility
Consult CMP & follow RACI guidelines -Primary contact to investigator site ( along with CMA) -Written, verbal, in-person, and phone communication -Use assertive communication style
Sponsor Roles/Responsibility
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Investigator Roles/Responsibility
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ICH GCP Guidelines
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FDA Code of Federal Regulations
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Clinical Monitoring Plan
CMP
Clinical Trial Cycle
Study Document Development (Protocol, IB, CRF)-> Investigator and Site Selection -> Budget Negotiation/CTA-> Investigator Meeting-> Study Site Initiation/RGL/Site Activation-> Patient Enrollment/Data Collection-> Study Monitoring-> Data Review/Cleaning-> Study Close-out-> Data Analysis/Final Clinical Study Report
Types of study design
Parallel group with placebo Dose comparison Crossover design Blinded vs open label
Study Design Elements
Study endpoints: Subject selection: Standardized tools:
Inclusion/exclusion criteria
Define subject population, protects subject safety, written to avoid confounding factors to study endpoints, monitor must verify subject eligibility
Data Quality
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Subject Safety
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Study procedures
Ensures consistency of data EKGs, lab tests & other diagnostics as safety measures Monitor must verify all study procedures are completed
Monitor AE/SAE Responsibility
CRA must verify all AEs/SAEs are correctly identified and reported
Protocol Sections
- Introduction 2. Objectives 3. Study Design 4. Duration of study 5. Study population 6. Study drug 7. Study procedures 8. Prior and concomitant treatment 9. AE reporting 10. Biostatistics 11. Ethics 12. Monitoring 13. Study Termination
Trusted Process Stages
PlanActivation QuickStart ProgramAccelerate QualityFinish
PlanActivation Stage (Study Design)
Request for Proposal (RFP) Quality risk and issue management Planning Quickstart Bid Defense Meeting (BDM) Desired outcome: formal award notification
QuickStart Phase (Study Planning)
Project award & Executed contract-> -Kick off meeting -Quality risk and issue management -engineering study execution -QSC Desired outcome: first patient (FP)
QuickStart Camp (QSC)
PM, CL, PS, and Sponsor attend Develop Clinical Monitoring Plan (CMP), Data Handling Plan (DHP), TMF Plan, Integrated Site Activation & Maintanence (ISAM) Plan
Pre-Study Visit (PSV) Purpose
• Evaluating the site before selection • Verify staff qualifications (education, training, experience) • Verify site resources and facilities meet protocol requirements • Review protocol and regulatory obligations with site • Confirm willingness to comply with protocol and regulatory requirements • Allow investigator to make an informed decision to conduct the study • Assess if the investigator can meet enrollment obligations • Discuss and evaluate potential risks • Assess willingness and ability to work with risk based monitoring – e.g., mix of targeted on-site monitoring visits and remote site management activities
Clinical Monitoring Plan (CMP)
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Site Selection Process
Site Identification –Risk identification begins at proposals and protocol development, but is established during Site Selection –Process to identify/pre-qualify potential investigators for study participation – Feasibility done by phone, online survey, face to face (if applicable) to share: • Confidentiality Disclosure Agreement (CDA) • Protocol synopsis or blinded study information • Potential Investigator Questionnaire (PIQ) • Investigator Compliance Check –Ensures investigators comply with governing regulatory agency standards – During Start-up and maintenance (each time a sub/investigator is added at site) – Review of international, national and/or local agencies • FDA list of debarred/disqualified/restricted investigators always included
Site Identification
–Process to identify/pre-qualify potential investigators for study participation – Feasibility done by phone, online survey, face to face (if applicable) to share: • Confidentiality Disclosure Agreement (CDA) • Protocol synopsis or blinded study information • Potential Investigator Questionnaire (PIQ)
Confidentiality Disclosure Agreement (CDA)
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Potential Investigator Questionnaire (PIQ)
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Investigator Compliance Check
–Ensures investigators comply with governing regulatory agency standards – During Start-up and maintenance (each time a sub/investigator is added at site) – Review of international, national and/or local agencies • FDA list of debarred/disqualified/restricted investigators always included
FDA list of debarred/disqualified/restricted investigators
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Importance of early risk identification (at investigator sites)
• Impact on Subject protection and data integrity • Risk identification may drive changes in trial conduct for one site or multiple sites • Risk control measures drive the monitoring strategy • Risk is assessed at all levels –System level: SOPs, computerized systems, personnel – Clinical trial level: trial design, data collection, informed consent process
PSV Risk Assessment
• Risk discussions during PSV should be documented • Sponsor decides which risks to reduce and/or accept • Risk strategy should be proportionate to risk significance
Proper Site Selection
• Choosing the wrong site(s) can result in: – Failure to meet the subject recruitment goals on time – Failure to close the study on time –Poor site relations – between Syneos Health and site as well as sponsor and site – Having to recruit additional sites during the study –Wasted time, effort and money • Risk discussions during PSV should be documented • Sponsor decides which risks to reduce and/or accept • Risk strategy should be proportionate to risk significance
PSV Requirements
Prior to the site’s selection each site is required to have a PSV (unless the requirement is waived) • PSVs may be conducted: By telephone (CMA/CRA responsibility) In person at the investigator site (CRA responsibility)
PSV Waiver
• Each site should have a PSV unless a waiver is approved • Following conditions must be met for waiver: – Investigator/site monitored for similar study in previous 12 months – No significant quality or compliance issues during previous visits – Investigator not on any debarment lists, no open warning letters (or similar) – No changes in PI and key personnel for subject procedures –Primary facility location unchanged, no satellite sites since most recent visit – No conflicts with ongoing studies, investigator available to oversee study –Access to (Electronic) Source Documentation unchanged & documented –Site/PI CDA fully signed and collected *Syneos Health Project Lead and Sponsor must approve a written waiver – PSV Waiver Form*
PSV Preparation
• Verify signed Confidentiality Disclosure Agreement (CDA) is in place • Review protocol or synopsis • Complete study/PSV specific training • Review Clinical Monitoring Plan (CMP) • Review PSV WI/ SOP • Review annotated PSV report – (incl. applicable tools, checklists or presentations) • Review feasibility / PIQ Questionnaire data • Confirm investigator compliance check completed • Determine all personnel and locations to be visited – (PI availability, site staff, exam rooms, storage, labs, satellite sites, etc.) • Schedule the visit, enter planned/confirmed date in CTMS • Send Agenda and confirmation letter • Prepare Regulatory documents as needed
6 Criteria for Serious Events (for SAE, SADR, SUSAR)
- Death 2. Life Threatening 3. Persistent/significant disability 4. Congenital abnormality 5. Hospitalization/prolongation of existing hospitalization 6. Important Medical Event (doctor has discretion to escalate the timeline)
IND Safety Report
Investigational New Drug Safety Report -IND number assigned
Medwatch Form
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Informed Consent Process
In depth review with subjects
Re-Consent Process
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