CCRA Adverse Event Management 1 — Questions and Answers
Question 1: What distinguishes a Serious Adverse Event (SAE) from a non-serious adverse event?
- An SAE is any adverse event reported by the subject
- An SAE results in death, is life-threatening, requires hospitalization, results in disability, or involves a congenital anomaly (Correct answer)
- An SAE must always be caused by the investigational product
- An SAE requires statistical significance to be classified as serious
Correct answer: An SAE results in death, is life-threatening, requires hospitalization, results in disability, or involves a congenital anomaly
An SAE meets at least one of the seriousness criteria defined in ICH E2A: death, life-threatening, inpatient hospitalization, persistent disability, congenital anomaly, or other medically important event.
Question 2: Under ICH E6(R2), an investigator must report a serious adverse event to the sponsor:
- Within 30 days of occurrence
- Immediately, typically within 24 hours of learning of the event (Correct answer)
- At the next scheduled monitoring visit
- Only if the event is considered related to the study drug
Correct answer: Immediately, typically within 24 hours of learning of the event
ICH E6(R2) section 4.11.1 requires investigators to report SAEs to the sponsor immediately upon learning of the event, except for SAEs exempted in the protocol.
Question 3: The term 'expectedness' in safety reporting refers to:
- Whether the adverse event was anticipated by the subject
- Whether the adverse event is listed in the Investigator Brochure or product labeling (Correct answer)
- The probability that the adverse event will recur
- Whether the subject gave prior consent for the risk
Correct answer: Whether the adverse event is listed in the Investigator Brochure or product labeling
Expectedness is determined by comparing the adverse event to events described in the reference safety information, typically the Investigator Brochure for investigational products.
Question 4: A 'SUSAR' stands for Suspected Unexpected Serious Adverse Reaction and must meet which THREE criteria?
- Serious, unexpected, and possibly related to the investigational product (Correct answer)
- Serious, severe, and occurring in more than one subject
- Unexpected, life-threatening, and causing hospitalization only
- Related, unexpected, and non-serious
Correct answer: Serious, unexpected, and possibly related to the investigational product
A SUSAR must be serious (meets seriousness criteria), unexpected (not in the IB), and have a reasonable suspected causal relationship to the investigational product.
Question 5: When the investigator's causality assessment differs from the sponsor's (sponsor considers event related, investigator does not), how should the discrepancy be handled for regulatory reporting?
- The investigator's assessment always overrides the sponsor's
- Both assessments should be reported, with the sponsor reporting based on the more conservative (related) assessment (Correct answer)
- The event does not need to be reported if the investigator disagrees
- A data safety monitoring board must resolve all discrepancies before reporting
Correct answer: Both assessments should be reported, with the sponsor reporting based on the more conservative (related) assessment
Regulatory guidance requires that when sponsor and investigator causality assessments differ, both must be documented, and the more conservative (causally related) assessment governs regulatory reporting requirements.
Question 6: Which form is used in the US to report individual safety reports (IND safety reports) to the FDA for clinical trials?
- FDA Form 3500A (MedWatch) (Correct answer)
- FDA Form 1571
- FDA Form 1572
- EMA CIOMS Form
Correct answer: FDA Form 3500A (MedWatch)
FDA Form 3500A (MedWatch) is used by sponsors to submit IND safety reports to the FDA for serious, unexpected, and suspected adverse drug reactions during clinical trials.
CCRA Adverse Event Management 1
What distinguishes a Serious Adverse Event (SAE) from a non-serious adverse event?