Study guide
7.1 Ethics Reporting, Approval Status and Version Control
ACRP CCRA Certified Clinical Research Associate Study Guide 2026 Exam
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1 Chapter 1: Exam Format, Eligibility and Registration
1.1 Exam Format, Eligibility and Current References 1.2 Registration, Fees and Candidate Decisions
2 Chapter 2: CRA Responsibilities and Study Planning
2.1 The CRA Role, Data Integrity and Product Oversight 2.2 Official Blueprint and Study Strategy
3 Chapter 3: Protocols, Endpoints and Trial Design
3.1 Protocol Elements and Endpoint Hierarchy 3.2 Endpoint Interpretation and Eligibility Rationale 3.3 Eligibility Verification and Trial Designs
4 Chapter 4: Bias Control, Blinding and Product Information
4.1 Bias, Randomisation and Comparator Controls 4.2 Unblinding and Investigator Brochure Content 4.3 Reference Safety Information and IB Updates
5 Chapter 5: Estimands and Device Instructions
5.1 Estimands and Intercurrent Events 5.2 Device Instructions, Configuration and Training
6 Chapter 6: Ethical Foundations and Independent Oversight
6.1 Ethical Foundations and the 2024 Declaration of Helsinki 6.2 Vulnerability, Voluntariness and Compensation 6.3 IRB/IEC Composition and Independent Review
7 Chapter 7: Ethics Communication and Informed Consent
7.1 Ethics Reporting, Approval Status and Version Control 7.2 Informed Consent Information and Meaningful Choice 7.3 Consent Documentation, Special Circumstances and Updates
8 Chapter 8: Recruitment, Retention and Confidentiality
8.1 Ethical Eligibility, Recruitment and Retention 8.2 Privacy, Confidentiality and Appropriate Access
9 Chapter 9: Safety Definitions and Classification
9.1 Adverse Event Definitions and Actual Life-Threatening Risk 9.2 Seriousness, Severity and Medical Importance 9.3 Causality, Expectedness and Reference Safety Information
10 Chapter 10: Safety Detection, Reporting and Oversight
10.1 Detecting Events, AESIs and Collection Windows 10.2 Expedited Reporting and the Sponsor Awareness Clock 10.3 Immediate Site Reporting and Independent Safety Oversight
11 Chapter 11: Follow-Up, Adherence and Conflicts
11.1 Safety Communications, Reconciliation and Follow-Up 11.2 Adherence, Discontinuation and Participant Choice 11.3 Conflicts of Interest and Prorated Payments
12 Chapter 12: Development Stages and Product Management
12.1 Nonclinical Background and Human Pharmacology 12.2 Exploratory, Confirmatory and Therapeutic-Use Studies 12.3 Product Storage, Labelling and Excursion Response
13 Chapter 13: Accountability, Integrity and Regulatory Status
13.1 Product Accountability and Adherence Calculations 13.2 Potential Fraud, Misconduct and Evidence Preservation 13.3 Submissions, Authorisation Status and Trial Reporting
14 Chapter 14: Current GCP Principles and Delegation
14.1 The Eleven Current GCP Principles 14.2 Proportionality and Investigator Oversight 14.3 Delegation, Qualifications and Task Authority
15 Chapter 15: Oversight, Protocol Control and Amendments
15.1 Clinical Oversight and Immediate-Hazard Changes 15.2 Deviation Classification and Resolution
16 Chapter 16: Implementation and Trial Responsibilities
16.1 Amendment Implementation and Communication 16.2 Sponsor, Investigator and Service-Provider Roles
17 Chapter 17: Quality Planning, Root Causes and CAPA
17.1 Quality Planning and Risk Management 17.2 Root Cause Analysis and CAPA Design 17.3 CAPA Implementation and Effectiveness Verification
18 Chapter 18: Risk Assessment and Monitoring Methods
18.1 Risk Assessment and Centralised Surveillance 18.2 Monitoring Methods and Source Review
19 Chapter 19: Quality Metrics, Plans and Communication
19.1 KRIs, Acceptable Ranges and Trial-Level Quality 19.2 Monitoring Plans, Co-Monitoring and Communication
20 Chapter 20: Site Qualification and Readiness
20.1 Site Qualification and Investigator Capacity 20.2 Recruitment Feasibility and Evidence-Based Site Selection 20.3 Site Readiness and Activity-Specific Release
21 Chapter 21: Initiation, Equipment and Supplies
21.1 Initiation Training and Readiness Walkthroughs 21.2 Equipment, Maintenance and Study Supplies
22 Chapter 22: Samples, Diagnostics and Financial Feasibility
22.1 Specimens, Diagnostic Results and Rater Quality 22.2 Contracts, Budgets and Operational Feasibility
23 Chapter 23: Interim Monitoring and Reporting
23.1 Interim Visit Preparation and Consent Review 23.2 Monitoring Eligibility, Safety and Products 23.3 Investigator Debrief and Monitoring Reports
24 Chapter 24: Essential Records, Audits and Findings
24.1 Essential Records and Site/Sponsor Reconciliation 24.2 Version History, Resolution Evidence and Noncompliance 24.3 Audits, Inspections and Closure Planning
25 Chapter 25: Close-Out, Retention and Destruction
25.1 Close-Out, Archiving and Continuing Obligations 25.2 Retention, Destruction and Long-Term Access
26 Chapter 26: Source Records and Good Documentation
26.1 Source Records and Foundational ALCOA Principles 26.2 Good Documentation, Completeness and Corrections 26.3 Source Access, Certified Copies and Context
27 Chapter 27: Electronic Systems, Metadata and Queries
27.1 EDC Design and Fit-for-Purpose Systems 27.2 Audit Trails, Electronic Outcomes and Device Choice 27.3 Queries, Coding and Supported Clinical Meaning
28 Chapter 28: Dataset Finalisation and Critical Data
28.1 Safety Reconciliation and Dataset Finalisation 28.2 Critical Data, Acquisition Tools and Interim Findings
7.1 Ethics Reporting, Approval Status and Version Control
Key Takeaways Explain This Topic AI
E6(R3) continuing review intervals are appropriate to participant risk.
A submission receipt is not proof that the intended document version is approved.
Approval problems require prompt clarification and a participant-protection plan.
Last updated: October 2026
Ethics Reporting, Approval Status and Version Control
Under ICH E6(R3), an investigator should not implement any deviation from, or changes to, the protocol without agreement by the sponsor and prior review and documented approval from the IRB/IEC of an amendment, except to remove an immediate hazard or for permitted purely logistical/administrative changes under applicable requirements. For substantive changes, obtain the appropriate ethics review and consent actions under the applicable framework and approved implementation plan.
Continuing oversight and loss of approval
E6(R3) requires continuing review at intervals appropriate to risk. It does not prescribe the old universal annual interval. Follow the committee's approval conditions and applicable requirements, tracking dates, progress updates, safety information and amendment decisions.
If approval expires, is suspended or is withdrawn, promptly establish the status with the investigator, sponsor and ethics committee. Do not assume a grace period or continue new enrolment without valid approval. Protect existing participants through an appropriate medically supervised transition; stopping treatment abruptly can itself cause harm. Document permitted care, notifications and the conditions for resumption. A monitor cannot retroactively extend ethical approval.
Prompt Reporting Requirements to the IRB/IEC
Investigators are legally and ethically obligated to submit timely reports to the IRB/IEC regarding events that may affect participant safety:
New information affecting participant risk: An event constitutes a UPIRTSO if it meets three distinct criteria: (1) it is unexpected in nature, severity, or frequency; (2) it is related or possibly related to participation in the research; and (3) it suggests that the research places subjects or others at a greater risk of harm than was previously known or recognized.
Protocol Deviations Implemented to Eliminate Immediate Hazards: When an investigator implements a change to eliminate an immediate hazard without prior IRB approval (e.g., immediately unblinding a patient or lowering a drug dose due to unexpected toxicities), document the action and rationale and promptly communicate through the relevant investigator/sponsor/IRB process, including an amendment or authority notification as appropriate under applicable requirements.
Serious Adverse Events (SAEs): Reported according to the IRB's specific written standard operating procedures (SOPs), typically focusing on events that are serious, unexpected, and related.
Non-Compliance: Any serious or continuing non-compliance with GCP, institutional policies, or IRB determinations.
CRA Verification Responsibilities for IRB Oversight
During site qualification, initiation, and interim monitoring visits, the CRA conducts rigorous source verification of IRB records in the Investigator Site File (ISF):
Tip
CRA Best Practice on Version Synchronization: Whenever the sponsor issues a revised protocol or ICF, check the date stamped on the IRB approval letter against the date the revised document was placed into clinical use at the site. A classic audit finding occurs when a site receives IRB approval on May 1 but continues consenting new subjects with the outdated ICF version until July because the coordinator failed to print the newly approved document.
Reconstructing a submission from the site file
Suppose the approval letter lists protocol version 3 and consent version 2, while the coordinator says consent version 3 was approved in the same meeting. Review the actual submission package, attachments, decision and subsequent correspondence. Determine whether the discrepancy is an incomplete letter, a missing decision or use of an unapproved form. Do not infer approval merely because the documents share a similar date.
The responsible investigator/sponsor function should seek clarification from the committee and assess any affected consent encounters. Preserve the original documents and correspondence; do not edit the committee's letter to make its version list match the binder. If approval is confirmed through a proper correction or clarification, retain that evidence with the historical sequence. If it is not confirmed, evaluate the participant-rights and compliance consequences and required follow-up.
When multiple sites rely on one ethics body, also confirm the scope of the decision and any local conditions. Central review does not automatically establish every site's activation status. A local institutional requirement can remain outstanding even though the protocol has a favourable central opinion. Keep permission, site readiness and actual implementation dates distinguishable in tracking and reports.
This example illustrates why an approval tracker needs a link to evidence and a responsible reviewer. A green status cell without a correct version and scope can hide a real protection gap. Timely reconciliation allows the site to resolve the issue before further use, rather than discovering it only during an inspection after many participants have been affected.
Official sources
Checked October 18, 2026: ICH E6(R3), Principles and Annex 1 , WMA Declaration of Helsinki, 2024 , ICH E11(R1) .