CPI Investigational Product Management & Drug Accountability 2 — Questions and Answers
Question 1: In a double-blind randomized controlled trial, an emergency unblinding for a single subject is medically necessary. What is the correct procedure?
- The principal investigator unilaterally decides the treatment assignment without documentation
- Follow the sponsor's emergency unblinding procedure, notify the sponsor promptly, and document the reason and outcome (Correct answer)
- Unblind the entire cohort to maintain consistency and fairness
- Delay unblinding until the next scheduled Data Safety Monitoring Board meeting
Correct answer: Follow the sponsor's emergency unblinding procedure, notify the sponsor promptly, and document the reason and outcome
Emergency unblinding must follow the sponsor's pre-defined procedure, be limited to the affected subject, and be documented with immediate notification to the sponsor to preserve trial integrity for other subjects.
Question 2: What is a drug reconciliation discrepancy?
- A difference between the approved protocol dose and the marketed dose of the drug
- A mismatch between the quantity of investigational product received, dispensed, returned, and destroyed (Correct answer)
- An error in the subject's medical history related to prior drug use
- A disagreement between the investigator and sponsor about optimal dosing
Correct answer: A mismatch between the quantity of investigational product received, dispensed, returned, and destroyed
A drug reconciliation discrepancy occurs when the arithmetic sum of product received minus product dispensed minus product returned/destroyed does not equal zero, indicating an unexplained quantity.
Question 3: How long must drug accountability records typically be retained after study completion under FDA regulations?
- 1 year after the trial ends
- Until the next FDA inspection, then they may be discarded
- 2 years after the study is approved or discontinued, or 2 years after the investigational drug is marketed (Correct answer)
- 5 years after the last subject's last visit
Correct answer: 2 years after the study is approved or discontinued, or 2 years after the investigational drug is marketed
Under 21 CFR 312.62, investigators must retain records for 2 years after a marketing application is approved or, if no application is filed, 2 years after the investigation is discontinued and FDA is notified.
Question 4: A subject returns 4 of 10 dispensed tablets at the next visit. The diary shows 5 doses taken. What should the site do?
- Accept the return count and make no further inquiry
- Document the discrepancy, query the subject about the missing tablet, and record the explanation in the accountability log (Correct answer)
- Report a serious adverse event for medication misuse
- Discontinue the subject from the trial immediately
Correct answer: Document the discrepancy, query the subject about the missing tablet, and record the explanation in the accountability log
A count mismatch (10 dispensed − 5 taken = 5 expected returns, but only 4 returned) requires site staff to query the subject, document the explanation, and record everything in the accountability log to resolve the discrepancy.
Question 5: Which of the following best describes 'blinded drug kits' used in a double-blind trial?
- Drug kits that have been visually inspected and confirmed safe for dispensing
- Packages where both active drug and placebo are made identical in appearance, smell, and labeling to conceal treatment assignment (Correct answer)
- Kits stored in a locked cabinet visible only to the pharmacist
- Drug containers that are sealed and cannot be opened until the subject is enrolled
Correct answer: Packages where both active drug and placebo are made identical in appearance, smell, and labeling to conceal treatment assignment
Blinded drug kits are manufactured so that active drug and placebo are indistinguishable to both the subject and site staff, preserving the blind and preventing bias in outcome assessment.
Question 6: What is the role of a sponsor's Clinical Research Associate (CRA) during a drug accountability monitoring visit?
- To dispense investigational product directly to enrolled subjects
- To verify that IP records are complete, accurate, and that physical inventory matches the accountability log (Correct answer)
- To update the informed consent form based on new safety data
- To randomize new subjects into the trial
Correct answer: To verify that IP records are complete, accurate, and that physical inventory matches the accountability log
During monitoring visits, the CRA reviews drug accountability records and performs a physical count of IP to verify that quantities on hand match what the log indicates should be remaining.
Question 7: An investigational product label for a US Phase II trial must include which of the following statements?
- "Approved by FDA for investigational use"
- "Caution: New Drug—Limited by Federal Law to Investigational Use" (Correct answer)
- "For Clinical Trial Use Only—No Adverse Events Expected"
- "Investigational Drug—Approved for Compassionate Use"
Correct answer: "Caution: New Drug—Limited by Federal Law to Investigational Use"
Per 21 CFR 312.6, investigational drug labels must bear the statement 'Caution: New Drug—Limited by Federal (or United States) law to investigational use' to clearly identify its investigational status.
CPI Investigational Product Management & Drug Accountability 2
In a double-blind randomized controlled trial, an emergency unblinding for a single subject is medically necessary.
What is the correct procedure?