CURR0104

Question 1

RACI

Answer 1

Responsible Accountable Consulted Informed

Question 2

CRA Roles/Resposibility

Answer 2

Consult CMP & follow RACI guidelines -Primary contact to investigator site ( along with CMA) -Written, verbal, in-person, and phone communication -Use assertive communication style

Question 3

Sponsor Roles/Responsibility

Answer 3

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Question 4

Investigator Roles/Responsibility

Answer 4

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Question 5

ICH GCP Guidelines

Answer 5

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Question 6

FDA Code of Federal Regulations

Answer 6

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Question 7

Clinical Monitoring Plan

Answer 7

CMP

Question 8

Clinical Trial Cycle

Answer 8

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

Question 9

Types of study design

Answer 9

Parallel group with placebo Dose comparison Crossover design Blinded vs open label

Question 10

Study Design Elements

Answer 10

Study endpoints: Subject selection: Standardized tools:

Question 11

Inclusion/exclusion criteria

Answer 11

Define subject population, protects subject safety, written to avoid confounding factors to study endpoints, monitor must verify subject eligibility

Question 12

Data Quality

Answer 12

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Question 13

Subject Safety

Answer 13

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Question 14

Study procedures

Answer 14

Ensures consistency of data EKGs, lab tests & other diagnostics as safety measures Monitor must verify all study procedures are completed

Question 15

Monitor AE/SAE Responsibility

Answer 15

CRA must verify all AEs/SAEs are correctly identified and reported

Question 16

Protocol Sections

Answer 16

1. 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

Question 17

Trusted Process Stages

Answer 17

PlanActivation QuickStart ProgramAccelerate QualityFinish

Question 18

PlanActivation Stage (Study Design)

Answer 18

Request for Proposal (RFP) Quality risk and issue management Planning Quickstart Bid Defense Meeting (BDM) Desired outcome: formal award notification

Question 19

QuickStart Phase (Study Planning)

Answer 19

Project award & Executed contract-> -Kick off meeting -Quality risk and issue management -engineering study execution -QSC Desired outcome: first patient (FP)

Question 20

QuickStart Camp (QSC)

Answer 20

PM, CL, PS, and Sponsor attend Develop Clinical Monitoring Plan (CMP), Data Handling Plan (DHP), TMF Plan, Integrated Site Activation & Maintanence (ISAM) Plan

Question 21

Pre-Study Visit (PSV) Purpose

Answer 21

• 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

Question 22

Clinical Monitoring Plan (CMP)

Answer 22

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Question 23

Site Selection Process

Answer 23

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

Question 24

Site Identification

Answer 24

–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)

Question 25

Confidentiality Disclosure Agreement (CDA)

Answer 25

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Question 26

Potential Investigator Questionnaire (PIQ)

Answer 26

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Question 27

Investigator Compliance Check

Answer 27

–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

Question 28

FDA list of debarred/disqualified/restricted investigators

Answer 28

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Question 29

Importance of early risk identification (at investigator sites)

Answer 29

• 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

Question 30

PSV Risk Assessment

Answer 30

• Risk discussions during PSV should be documented • Sponsor decides which risks to reduce and/or accept • Risk strategy should be proportionate to risk significance

Question 31

Proper Site Selection

Answer 31

• 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

Question 32

PSV Requirements

Answer 32

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)

Question 33

PSV Waiver

Answer 33

• 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\*

Question 34

PSV Preparation

Answer 34

• 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

Question 35

6 Criteria for Serious Events (for SAE, SADR, SUSAR)

Answer 35

1. 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)

Question 36

IND Safety Report

Answer 36

Investigational New Drug Safety Report -IND number assigned

Question 37

Medwatch Form

Answer 37

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Question 38

Informed Consent Process

Answer 38

In depth review with subjects

Question 39

Re-Consent Process

Answer 39

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