CCRA Certified Clinical Research Associate 4 — Questions and Answers
Question 1: What is the key difference between an adverse event (AE) and an adverse drug reaction (ADR) in clinical trial terminology?
- An AE is always serious while an ADR is never serious
- An ADR implies a causal relationship to the investigational product, whereas an AE does not require causality (Correct answer)
- An ADR is only used in post-marketing surveillance
- An AE must be reported to the FDA while an ADR is reported only to the IRB
Correct answer: An ADR implies a causal relationship to the investigational product, whereas an AE does not require causality
An ADR requires at least a reasonable possibility of a causal relationship to the study drug, while an AE is any untoward medical occurrence regardless of causality.
Question 2: During source data verification (SDV), the CRA finds that a lab value in the CRF was changed without documentation. What does this indicate?
- Acceptable site practice to maintain clean data
- A potential data integrity issue that must be queried and documented (Correct answer)
- A minor clerical error that can be verbally corrected
- Evidence of fraud that requires immediate trial suspension
Correct answer: A potential data integrity issue that must be queried and documented
Undocumented CRF changes violate ALCOA+ data integrity principles and must be investigated, queried, and documented in the monitoring report.
Question 3: Which regulatory document grants the FDA authority to inspect clinical investigators conducting trials under an IND?
- 21 CFR Part 11 — Electronic Records
- 21 CFR Part 312 — IND Regulations (Correct answer)
- 21 CFR Part 54 — Financial Disclosure
- 21 CFR Part 820 — Quality System Regulation
Correct answer: 21 CFR Part 312 — IND Regulations
21 CFR Part 312 establishes IND requirements and grants FDA the authority to inspect clinical investigators and their records.
Question 4: A site coordinator asks a CRA if she can enter data into the CRF on behalf of the investigator to save time. What should the CRA advise?
- Yes, if the investigator verbally approves later
- Site staff may enter data if authorized and trained, but the investigator must review and sign off on all entries per protocol (Correct answer)
- No, only the principal investigator may ever enter any CRF data
- Yes, as long as the CRA counter-signs the entries
Correct answer: Site staff may enter data if authorized and trained, but the investigator must review and sign off on all entries per protocol
Sub-investigators and coordinators may enter CRF data if authorized by the investigator and documented on the site's delegation log, with the investigator retaining oversight responsibility.
Question 5: What is the primary purpose of the Investigator's Brochure (IB)?
- To serve as the subject recruitment advertisement
- To compile and summarize clinical and nonclinical data relevant to the investigational product for investigators (Correct answer)
- To replace the protocol as the definitive trial design document
- To provide financial terms between the sponsor and investigator
Correct answer: To compile and summarize clinical and nonclinical data relevant to the investigational product for investigators
The IB compiles all relevant preclinical and clinical information about the investigational product to inform investigators about risks, properties, and safe use.
Question 6: A subject reports a new, unexpected, drug-related serious adverse event. According to ICH E6, within what timeframe must the investigator report this to the sponsor?
- Within 24 hours of becoming aware (Correct answer)
- Within 48 hours of becoming aware
- Within 7 calendar days
- Within 15 calendar days
Correct answer: Within 24 hours of becoming aware
ICH E6(R2) requires investigators to report all serious adverse events to the sponsor immediately, and no later than 24 hours of their becoming aware of the event.
Question 7: What is the role of a Central IRB (cIRB) in a multi-site clinical trial?
- To replace the FDA as the primary regulatory reviewer
- To provide a single ethics review that can cover multiple sites, streamlining oversight (Correct answer)
- To monitor site compliance with the protocol on behalf of the sponsor
- To adjudicate disputes between investigators and the sponsor
Correct answer: To provide a single ethics review that can cover multiple sites, streamlining oversight
A central IRB conducts a single ethics review applicable to multiple participating sites, reducing duplication and streamlining the approval process.
CCRA Certified Clinical Research Associate 4
What is the key difference between an adverse event (AE) and an adverse drug reaction (ADR) in clinical trial terminology?