ACRP CCRC Advanced Prep: Master
Clinical Trial Operations & Regulatory
Compliance Practice Questions
Subject: Clinical Trial Operations, Regulatory Compliance, and Ethical
Considerations
Question 1: During a Phase II oncology trial, a site coordinator notes that a subject has
experienced a Grade 3 adverse event (AE) that was not listed in the current Investigator’s
Brochure (IB) but is documented as a known risk in the protocol’s background section. How
should this event be categorized and reported?
A) It is an Unexpected Adverse Event; report to the sponsor within 24 hours.
B) It is an Expected Adverse Event because it is in the protocol; no expedited reporting is
required.
C) It is a Serious Adverse Event (SAE); report to the IRB and sponsor according to the protocol-
defined timeline for unexpected events.
D) It is a Suspected Unexpected Serious Adverse Reaction (SUSAR); report immediately to the
FDA only.
Correct Answer: C) It is a Serious Adverse Event (SAE); report to the IRB and sponsor
according to the protocol-defined timeline for unexpected events.
Explanation: The definition of "expectedness" in clinical trials is dictated by the Investigator’s
Brochure (IB), not the protocol background. Because the event is not in the IB, it is considered
"unexpected." Since it is a Grade 3 AE (often meeting criteria for an SAE depending on
intervention), it must be reported to the sponsor and IRB based on the IB's risk profile.
Question 2: An investigator decides to implement a minor change to the study visit schedule to
improve subject retention. This change does not affect the safety of the subjects or the integrity
of the data. What is the most appropriate regulatory action?
A) Implement the change immediately and notify the IRB during the next continuing review.
B) Submit a formal protocol amendment to the IRB and sponsor, and wait for written approval
before implementation.
C) Notify the sponsor via email and proceed, as it is a non-substantial modification.
D) Document the change in the site’s internal SOPs and proceed without IRB notification.
,Correct Answer: B) Submit a formal protocol amendment to the IRB and sponsor, and wait
for written approval before implementation.
Explanation: According to ICH-GCP, any modification to the protocol, regardless of its
perceived impact, must be submitted as a protocol amendment to the IRB/IEC and sponsor.
Implementation prior to IRB approval is a protocol violation.
Question 3: A monitor identifies that a site has been using a "certified copy" of a paper source
document, but the original was destroyed by the research assistant to "save space." Which
ALCOA+ principle has been violated?
A) Attributable
B) Contemporaneous
C) Enduring
D) Original
Correct Answer: D) Original
Explanation: Under ALCOA+ (Accurate, Legible, Contemporaneous, Original, Attributable), a
certified copy is only valid if the original is maintained or if the process of creating the certified
copy is validated. Destroying the original without a validated process invalidates the "Original"
status of the data record.
Question 4: You are reviewing a protocol and notice that the randomization schedule is being
held by the Principal Investigator (PI) on-site for "emergency use." What is the correct protocol
compliance action?
A) This is acceptable as long as the PI has a signed confidentiality agreement.
B) The randomization code must be held by the sponsor or an unblinded third party to prevent
bias.
C) The PI may hold the code but must store it in a double-locked cabinet.
D) The PI may hold the code if it is documented in the delegation of authority log.
Correct Answer: B) The randomization code must be held by the sponsor or an unblinded
third party to prevent bias.
Explanation: To maintain the integrity of a blinded study, the randomization schedule must be
concealed from those involved in the conduct of the trial (investigators/coordinators). PI access
to the code introduces potential selection and observer bias.
, Question 5: A potential study subject is unable to read the Informed Consent Form (ICF) due to a
visual impairment. How should the informed consent process be managed to remain compliant?
A) Use a legally authorized representative (LAR) to sign the document in all cases.
B) Read the entire ICF to the subject in the presence of an impartial witness, and have the
witness sign the document.
C) Provide an audio recording of the ICF and have the subject sign it independently.
D) Ask a family member to read the ICF and sign on behalf of the subject.
Correct Answer: B) Read the entire ICF to the subject in the presence of an impartial
witness, and have the witness sign the document.
Explanation: For subjects who cannot read the ICF, the process requires an impartial witness to
observe the oral presentation of the consent form. The subject provides consent (or mark), and
the witness signs to attest that the information was accurately conveyed and understood.
Question 6: During a monitoring visit, it is discovered that study staff training for a protocol
amendment was conducted, but the documentation is missing the date of training. How should
this be corrected?
A) Add the date today and add a note to the file explaining that it was performed previously.
B) Create a new training log entry, backdate it to the actual date of training, and attach a memo
to the file.
C) Document the oversight in a CAPA plan and have the staff member re-sign the training log
with the current date.
D) Discard the incomplete log and replace it with a new one signed by the PI.
Correct Answer: C) Document the oversight in a CAPA plan and have the staff member re-
sign the training log with the current date.
Explanation: Backdating (Option B) is considered fraud/misconduct. The only compliant way to
fix a missing date is to document the error via a Corrective and Preventive Action (CAPA) plan
and ensure the training is re-verified or properly documented at the time of discovery.
Question 7: A clinical trial entity, specifically a Data Monitoring Committee (DMC), has
requested an unblinded report of interim safety data. What is the coordinator’s role in this
process?
A) Prepare the unblinded report and send it directly to the DMC.
Clinical Trial Operations & Regulatory
Compliance Practice Questions
Subject: Clinical Trial Operations, Regulatory Compliance, and Ethical
Considerations
Question 1: During a Phase II oncology trial, a site coordinator notes that a subject has
experienced a Grade 3 adverse event (AE) that was not listed in the current Investigator’s
Brochure (IB) but is documented as a known risk in the protocol’s background section. How
should this event be categorized and reported?
A) It is an Unexpected Adverse Event; report to the sponsor within 24 hours.
B) It is an Expected Adverse Event because it is in the protocol; no expedited reporting is
required.
C) It is a Serious Adverse Event (SAE); report to the IRB and sponsor according to the protocol-
defined timeline for unexpected events.
D) It is a Suspected Unexpected Serious Adverse Reaction (SUSAR); report immediately to the
FDA only.
Correct Answer: C) It is a Serious Adverse Event (SAE); report to the IRB and sponsor
according to the protocol-defined timeline for unexpected events.
Explanation: The definition of "expectedness" in clinical trials is dictated by the Investigator’s
Brochure (IB), not the protocol background. Because the event is not in the IB, it is considered
"unexpected." Since it is a Grade 3 AE (often meeting criteria for an SAE depending on
intervention), it must be reported to the sponsor and IRB based on the IB's risk profile.
Question 2: An investigator decides to implement a minor change to the study visit schedule to
improve subject retention. This change does not affect the safety of the subjects or the integrity
of the data. What is the most appropriate regulatory action?
A) Implement the change immediately and notify the IRB during the next continuing review.
B) Submit a formal protocol amendment to the IRB and sponsor, and wait for written approval
before implementation.
C) Notify the sponsor via email and proceed, as it is a non-substantial modification.
D) Document the change in the site’s internal SOPs and proceed without IRB notification.
,Correct Answer: B) Submit a formal protocol amendment to the IRB and sponsor, and wait
for written approval before implementation.
Explanation: According to ICH-GCP, any modification to the protocol, regardless of its
perceived impact, must be submitted as a protocol amendment to the IRB/IEC and sponsor.
Implementation prior to IRB approval is a protocol violation.
Question 3: A monitor identifies that a site has been using a "certified copy" of a paper source
document, but the original was destroyed by the research assistant to "save space." Which
ALCOA+ principle has been violated?
A) Attributable
B) Contemporaneous
C) Enduring
D) Original
Correct Answer: D) Original
Explanation: Under ALCOA+ (Accurate, Legible, Contemporaneous, Original, Attributable), a
certified copy is only valid if the original is maintained or if the process of creating the certified
copy is validated. Destroying the original without a validated process invalidates the "Original"
status of the data record.
Question 4: You are reviewing a protocol and notice that the randomization schedule is being
held by the Principal Investigator (PI) on-site for "emergency use." What is the correct protocol
compliance action?
A) This is acceptable as long as the PI has a signed confidentiality agreement.
B) The randomization code must be held by the sponsor or an unblinded third party to prevent
bias.
C) The PI may hold the code but must store it in a double-locked cabinet.
D) The PI may hold the code if it is documented in the delegation of authority log.
Correct Answer: B) The randomization code must be held by the sponsor or an unblinded
third party to prevent bias.
Explanation: To maintain the integrity of a blinded study, the randomization schedule must be
concealed from those involved in the conduct of the trial (investigators/coordinators). PI access
to the code introduces potential selection and observer bias.
, Question 5: A potential study subject is unable to read the Informed Consent Form (ICF) due to a
visual impairment. How should the informed consent process be managed to remain compliant?
A) Use a legally authorized representative (LAR) to sign the document in all cases.
B) Read the entire ICF to the subject in the presence of an impartial witness, and have the
witness sign the document.
C) Provide an audio recording of the ICF and have the subject sign it independently.
D) Ask a family member to read the ICF and sign on behalf of the subject.
Correct Answer: B) Read the entire ICF to the subject in the presence of an impartial
witness, and have the witness sign the document.
Explanation: For subjects who cannot read the ICF, the process requires an impartial witness to
observe the oral presentation of the consent form. The subject provides consent (or mark), and
the witness signs to attest that the information was accurately conveyed and understood.
Question 6: During a monitoring visit, it is discovered that study staff training for a protocol
amendment was conducted, but the documentation is missing the date of training. How should
this be corrected?
A) Add the date today and add a note to the file explaining that it was performed previously.
B) Create a new training log entry, backdate it to the actual date of training, and attach a memo
to the file.
C) Document the oversight in a CAPA plan and have the staff member re-sign the training log
with the current date.
D) Discard the incomplete log and replace it with a new one signed by the PI.
Correct Answer: C) Document the oversight in a CAPA plan and have the staff member re-
sign the training log with the current date.
Explanation: Backdating (Option B) is considered fraud/misconduct. The only compliant way to
fix a missing date is to document the error via a Corrective and Preventive Action (CAPA) plan
and ensure the training is re-verified or properly documented at the time of discovery.
Question 7: A clinical trial entity, specifically a Data Monitoring Committee (DMC), has
requested an unblinded report of interim safety data. What is the coordinator’s role in this
process?
A) Prepare the unblinded report and send it directly to the DMC.
