2.1 Investigator and Site Responsibilities

Investigator oversight, delegation, qualified staff, adequate resources, and control of the trial at the site.

2.2 Sponsor and CRO Responsibilities

Understanding sponsor accountability, CRO partnerships, quality management systems, and how sponsor oversight impacts site operations.

2.3 IRB/IEC Oversight

Understanding ethics committee oversight, the approval process, ongoing communications, and how to maintain a productive partnership with your IRB/IEC.

2.4 Investigator Qualifications, Training, and Resources

Understanding what makes an investigator qualified, how to demonstrate competence, and ensuring adequate resources for quality trial conduct.

3.1 The Informed Consent Process

Understanding informed consent as an ongoing process, from first contact through trial completion, with practical guidance on documentation and communication.

3.2 Vulnerable Populations and Consent Documentation

Special considerations and documentation standards for vulnerable populations and complex scenarios.

4.1 Protocol Conduct, Deviations, and Amendments

Following the approved protocol, managing deviations, and implementing amendments responsibly.

4.2 Investigational Product Accountability

Receipt, storage, dispensing, reconciliation, and return/destruction per E6(R3).

4.3 Randomization and Unblinding

Following randomization procedures and ensuring capability to unblind without delay; document premature unblinding (E6(R3) 2.11).

4.4 End of Participation and Early Termination/Suspension

Managing participant withdrawal/end of participation and investigator responsibilities for early termination/suspension (E6(R3) 2.6, 2.9).

5.1 AE/SAE/SUSAR: Definitions and Reporting

Safety event definitions and fundamentals of reporting obligations and pathways.

5.2 Safety Management and Timelines

Managing safety information flow and meeting reporting timelines and documentation requirements.

5.3 Medical Care of Trial Participants

Qualified medical oversight, appropriate care for AEs and lab deviations, and communication with primary physicians per participant permission (E6(R3) 2.7.1).

6.1 Source Data, CRF/eCRF, and ALCOA++

Data integrity expectations and practical application of ALCOA++ across source and CRFs.

6.2 Electronic Systems and Validation

Fit-for-purpose validation, access control, audit trails, and data governance for eSystems.

7.1 Data Governance Overview and Lifecycle

Proportionate governance across the full data lifecycle; confidentiality, integrity, and traceability responsibilities (E6(R3) 4.2).

7.2 Safeguarding Blinding in Data Handling

Define roles, responsibilities, and procedures for access to unblinded information; mitigation against inadvertent unblinding (E6(R3) 4.1).

7.3 Computerized Systems: Responsibilities and User Management

Clarifies responsibilities and expectations for computerized systems: training, security, validation, release, failure handling, support, and user management (E6(R3) 4.3).

8.1 QMS, RBQM, and Quality by Design

Establishing a quality management system with risk-proportionate controls and QbD.

8.2 Monitoring: Centralized and Onsite

Designing proportionate monitoring strategies, including centralized and onsite activities.

8.3 Risk Assessment and Mitigation

Identifying, assessing, and mitigating risks, with ongoing review and CAPA where needed.

9.1 Essential Documents and the TMF

Organizing and maintaining essential documents in the TMF to reconstruct trials.

9.2 Inspection Readiness and Noncompliance

Preparing for inspections, addressing noncompliance, and driving effective CAPA.

9.3 Study Completion and Reporting

Provide all required reports to sponsor; submit final report/summary to IRB/IEC and regulators as required (E6(R3) 2.13).

2.1 Investigator and Site Responsibilities

Investigator oversight, delegation, qualified staff, adequate resources, and control of the trial at the site.

2.2 Sponsor and CRO Responsibilities

Understanding sponsor accountability, CRO partnerships, quality management systems, and how sponsor oversight impacts site operations.

2.3 IRB/IEC Oversight

Understanding ethics committee oversight, the approval process, ongoing communications, and how to maintain a productive partnership with your IRB/IEC.

2.4 Investigator Qualifications, Training, and Resources

Understanding what makes an investigator qualified, how to demonstrate competence, and ensuring adequate resources for quality trial conduct.

3.1 The Informed Consent Process

Understanding informed consent as an ongoing process, from first contact through trial completion, with practical guidance on documentation and communication.

3.2 Vulnerable Populations and Consent Documentation

Special considerations and documentation standards for vulnerable populations and complex scenarios.

4.1 Protocol Conduct, Deviations, and Amendments

Following the approved protocol, managing deviations, and implementing amendments responsibly.

4.2 Investigational Product Accountability

Receipt, storage, dispensing, reconciliation, and return/destruction per E6(R3).

4.3 Randomization and Unblinding

Following randomization procedures and ensuring capability to unblind without delay; document premature unblinding (E6(R3) 2.11).

4.4 End of Participation and Early Termination/Suspension

Managing participant withdrawal/end of participation and investigator responsibilities for early termination/suspension (E6(R3) 2.6, 2.9).

5.1 AE/SAE/SUSAR: Definitions and Reporting

Safety event definitions and fundamentals of reporting obligations and pathways.

5.2 Safety Management and Timelines

Managing safety information flow and meeting reporting timelines and documentation requirements.

5.3 Medical Care of Trial Participants

Qualified medical oversight, appropriate care for AEs and lab deviations, and communication with primary physicians per participant permission (E6(R3) 2.7.1).

6.1 Source Data, CRF/eCRF, and ALCOA++

Data integrity expectations and practical application of ALCOA++ across source and CRFs.

6.2 Electronic Systems and Validation

Fit-for-purpose validation, access control, audit trails, and data governance for eSystems.

7.1 Data Governance Overview and Lifecycle

Proportionate governance across the full data lifecycle; confidentiality, integrity, and traceability responsibilities (E6(R3) 4.2).

7.2 Safeguarding Blinding in Data Handling

Define roles, responsibilities, and procedures for access to unblinded information; mitigation against inadvertent unblinding (E6(R3) 4.1).

7.3 Computerized Systems: Responsibilities and User Management

Clarifies responsibilities and expectations for computerized systems: training, security, validation, release, failure handling, support, and user management (E6(R3) 4.3).

8.1 QMS, RBQM, and Quality by Design

Establishing a quality management system with risk-proportionate controls and QbD.

8.2 Monitoring: Centralized and Onsite

Designing proportionate monitoring strategies, including centralized and onsite activities.

8.3 Risk Assessment and Mitigation

Identifying, assessing, and mitigating risks, with ongoing review and CAPA where needed.

9.1 Essential Documents and the TMF

Organizing and maintaining essential documents in the TMF to reconstruct trials.

9.2 Inspection Readiness and Noncompliance

Preparing for inspections, addressing noncompliance, and driving effective CAPA.

9.3 Study Completion and Reporting

Provide all required reports to sponsor; submit final report/summary to IRB/IEC and regulators as required (E6(R3) 2.13).