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ICH E6(R3) GCP practice questions

These questions are original. Each has four options and one best answer, and is written against the ICH E6(R3) guideline (Step 4, 6 January 2025) and related ICH guidelines. The source section is cited for each answer.

Practise with scoring and progress

  1. An IRB/IEC is being set up for a trial site. Per ICH GCP, which composition is the minimum acceptable?

    • A. Three members, all physicians
    • B. Five members, incl. one non-scientific member and one independent of the institution
    • C. Seven members, majority lay
    • D. Five members, all independent of the institution
    Show answer

    Answer: B.

    ICH E6(R3) 1.3.1 (recommended: >=5 members, >=1 whose primary interest is not medical sciences, >=1 independent of institution/site); E6(R2) 3.2.1.

  2. An investigator learns of a serious adverse event not exempted by the protocol. What should they do?

    • A. Report it in the next annual safety report
    • B. Report it to the sponsor immediately
    • C. Report only if judged related
    • D. Report directly to the regulator within 30 days
    Show answer

    Answer: B.

    ICH E6(R3) 2.7.2(b) 'reported immediately... to the sponsor' with causality assessment; E6(R2) 4.11.1.

  3. A sponsor receives a fatal, unexpected suspected adverse drug reaction in a clinical trial. Under ICH E2A, the initial expedited report is due within:

    • A. 24 hours
    • B. 7 calendar days, with a complete report within 8 further days
    • C. 15 calendar days
    • D. 30 days
    Show answer

    Answer: B.

    ICH E2A section III.A. (Other serious unexpected ADRs: 15 calendar days.)

  4. Under ICH E6(R3), how long must investigators retain essential records?

    • A. Exactly 2 years after marketing approval
    • B. 5 years after trial end
    • C. For the period required by applicable regulatory requirements, or until the sponsor says they are no longer needed, whichever is longest
    • D. 25 years in all regions
    Show answer

    Answer: C.

    ICH E6(R3) 2.12.12. Teaching point: the fixed "2 years after last marketing approval" rule in E6(R2) 4.9.5 is no longer the R3 wording; EU CTR 536/2014 Art. 58(1): sponsor and investigator archive TMF content for at least 25 years after end of trial.

  5. Per ICH GCP, a systematic and independent examination of trial activities and documents, to check compliance with protocol, SOPs, GCP and regulations, is called:

    • A. Monitoring
    • B. Inspection
    • C. Audit
    • D. Source data verification
    Show answer

    Answer: C.

    ICH E6(R3) Glossary 'Audit'; E6(R2) 1.17. (Inspection = by regulatory authorities, 1.29.)

  6. Under ICH E6(R3), how are 'critical to quality factors' of a trial characterised?

    • A. Attributes of a trial that are fundamental to participant protection, the reliability and interpretability of results, and the decisions made from them
    • B. The data points that the sponsor's statistician expects to be missing most often
    • C. The procedures that are most expensive to perform and so need the closest source data verification at every site
    • D. Any protocol requirement that the IRB/IEC has asked to review in detail before approval
    Show answer

    Answer: A.

    ICH E6(R3) Principle 6.2 (Principles of GCP, Principle 6). Principle 6.2 defines critical to quality factors by their importance to participant protection and result reliability, not by cost, missingness or IRB/IEC interest. They are to be identified prospectively.

  7. A sponsor has set a trial-level quality tolerance limit for a critical to quality factor, and the limit is exceeded during the trial. According to ICH E6(R3), what should happen?

    • A. The trial must be suspended until the regulatory authority has approved a protocol amendment
    • B. An evaluation should be performed to determine whether there is a possible systemic issue and whether action is needed
    • C. The excess should be recorded as a protocol deviation at each affected site and no further evaluation is expected
    • D. The limit should be widened so that the trial returns to being within its pre-specified range
    Show answer

    Answer: B.

    ICH E6(R3) 3.10.1.3 (Risk Control). Section 3.10.1.3 treats pre-specified acceptable ranges as triggers for evaluation of a possible systemic issue; it does not require automatic suspension, and does not suggest relaxing the limit.

  8. A sponsor transfers a number of its trial-related activities to a service provider under a written agreement. Which statement is consistent with ICH E6(R3)?

    • A. Responsibility for the transferred activities passes to the service provider once the agreement is signed
    • B. Responsibility passes to the service provider, but the sponsor must keep a copy of the provider's SOPs
    • C. The ultimate responsibility for the sponsor's trial-related activities, including participant protection and data reliability, resides with the sponsor
    • D. The investigator becomes responsible for the oversight of the service provider's transferred activities
    Show answer

    Answer: C.

    ICH E6(R3) 3.6.6. Transfer of activities does not transfer ultimate responsibility. Oversight of important transferred activities, including those subcontracted onward, is also required (3.6.9).

  9. Under the E6(R3) data governance provisions, what is expected of the sponsor regarding control of data captured in data acquisition tools?

    • A. The sponsor should hold exclusive control of the data so that site staff cannot alter them
    • B. The sponsor should not have exclusive control of the data, in order to prevent undetectable changes
    • C. Control may rest with either party, provided the audit trail is switched on only after database lock
    • D. The service provider hosting the system should have exclusive control, to keep the sponsor blinded
    Show answer

    Answer: B.

    ICH E6(R3) 3.16.1(l). Section 3.16.1(l) says the sponsor should not hold exclusive control, so changes cannot go undetected. Option A states the opposite.

  10. An investigator delegates several trial-related activities to staff and to an external service provider. Which statement reflects ICH E6(R3)?

    • A. Responsibility for delegated activities passes to the delegate once they have been trained
    • B. The sponsor assumes oversight of delegated activities as soon as it has identified the service provider
    • C. The investigator's responsibility is limited to the activities that the investigator performs personally
    • D. The investigator retains the ultimate responsibility and should maintain appropriate oversight of those undertaking the delegated activities
    Show answer

    Answer: D.

    ICH E6(R3) 2.3.1. Section 2.3.1 keeps ultimate responsibility with the investigator, with oversight proportionate to data importance and risk. The sponsor may support identification of a provider, but the investigator makes the final decision.

  11. An investigator departs from the protocol to eliminate an immediate hazard to trial participants. What does ICH E6(R3) say about informing the sponsor?

    • A. The investigator should inform the sponsor promptly
    • B. The sponsor need only be told at the next scheduled monitoring visit
    • C. The investigator must wait for the sponsor's written agreement before acting
    • D. The sponsor is informed only if the deviation is later classified as serious noncompliance
    Show answer

    Answer: A.

    ICH E6(R3) 2.5.4. Section 2.5.4 permits deviation only where necessary to eliminate an immediate hazard, with prompt notice to the sponsor. 2.5.5 adds reporting to the IRB/IEC and, where applicable, regulatory authorities.

  12. In ICH E6(R3), which party is responsible for expediting the reporting of SUSARs to the regulatory authority(ies)?

    • A. The investigator, within the time period specified in the protocol
    • B. The sponsor, in accordance with the applicable regulatory requirements and ICH E2A
    • C. The IRB/IEC, once it has reviewed the investigator's causality assessment
    • D. The service provider holding the safety database, which then carries the sponsor's responsibility
    Show answer

    Answer: B.

    ICH E6(R3) 3.13.3(b). Expedited SUSAR reporting to regulators is a sponsor task (3.13.3(b)); the investigator reports to the sponsor. Even if a provider is used, the sponsor keeps ultimate responsibility (3.6.6).

  13. Where an investigator provides trial participants with equipment for data acquisition, what does ICH E6(R3) require of the investigator/institution?

    • A. Participants must be given the sponsor's validation report for the equipment
    • B. Only the sponsor is expected to address the equipment, as it is a sponsor-deployed system
    • C. Traceability should be maintained and participants should be provided with appropriate training
    • D. The equipment should be collected after each visit so that participants cannot alter data
    Show answer

    Answer: C.

    ICH E6(R3) 2.12.10(d). Section 2.12.10(d) places traceability and participant training on the investigator/institution where the investigator supplies the equipment.

  14. According to Appendix A of ICH E6(R3), how often should the Investigator's Brochure be reviewed?

    • A. Only when the sponsor submits a new marketing authorisation application
    • B. At least every two years, in line with the IRB/IEC continuing review cycle
    • C. Only when the IRB/IEC requests a revision
    • D. At least annually, and revised as necessary in compliance with the sponsor's documented procedures
    Show answer

    Answer: D.

    ICH E6(R3) Appendix A, A.1.1. A.1.1 sets at least annual review, with more frequent revision possible depending on development stage and new information. The sponsor is responsible for ensuring an up-to-date IB.

  15. Which statement about managing essential records is stated in Appendix C of ICH E6(R3)?

    • A. The sponsor and investigator/institution should maintain a record of where essential records are located, including source records
    • B. Only the sponsor needs a location record, as the trial master file covers the investigator's records
    • C. Source records are excluded from location records because they stay in clinical practice systems
    • D. Location records are needed only for paper records, since electronic records are searchable by default
    Show answer

    Answer: A.

    ICH E6(R3) Appendix C, C.2.4. C.2.4 applies to both parties, covers source records, and is media-neutral (irrespective of the type of media used).

Practise with scoring and progress