CCRA Adverse Event Management 2 — Questions and Answers
Question 1: An 'adverse event of special interest' (AESI) differs from a standard SAE in that it:
- Is always fatal
- Is predefined in the protocol as requiring expedited reporting regardless of standard seriousness criteria (Correct answer)
- Can only occur in Phase I trials
- Does not require documentation in the CRF
Correct answer: Is predefined in the protocol as requiring expedited reporting regardless of standard seriousness criteria
AESIs are protocol-specified events considered scientifically important for the product's benefit-risk assessment and require enhanced or expedited monitoring and reporting even if not classified as serious.
Question 2: What is the difference between an Adverse Event (AE) and an Adverse Drug Reaction (ADR)?
- An AE is always more serious than an ADR
- An ADR implies at least a possible causal relationship to the study drug, while an AE does not require causality (Correct answer)
- An ADR applies only to marketed drugs, not investigational products
- An AE requires hospitalization while an ADR does not
Correct answer: An ADR implies at least a possible causal relationship to the study drug, while an AE does not require causality
An AE is any untoward medical occurrence temporally associated with study drug use, regardless of causality; an ADR implies a causal relationship has been at least reasonably suspected.
Question 3: The 15-day reporting clock for an expedited IND safety report begins when:
- The subject reports symptoms to the site staff
- The sponsor first receives minimum valid safety information about the SUSAR (Correct answer)
- The CRA documents the event in the monitoring report
- The IRB is notified of the event
Correct answer: The sponsor first receives minimum valid safety information about the SUSAR
The 15-calendar-day regulatory reporting clock starts when the sponsor receives the minimum information required for a valid case (identifiable patient, reporter, suspect drug, and adverse event).
Question 4: A 'protocol-defined SAE exemption' means:
- The sponsor can waive all SAE reporting for a trial
- Certain SAEs anticipated by the disease or procedure do not require expedited reporting to the sponsor if specified in the protocol (Correct answer)
- IRB approval is not required for exempt SAEs
- Subjects are not informed about exempt SAEs
Correct answer: Certain SAEs anticipated by the disease or procedure do not require expedited reporting to the sponsor if specified in the protocol
Protocols may pre-specify SAEs that are expected outcomes of the underlying disease or procedure, exempting them from the standard immediate reporting requirement to reduce reporting burden.
Question 5: Which entity is responsible for assessing the causality (relatedness) of an adverse event to the investigational product?
- The subject or patient
- The CRA during the monitoring visit
- The investigator, and separately the sponsor's medical monitor (Correct answer)
- The IRB during the annual review
Correct answer: The investigator, and separately the sponsor's medical monitor
Both the investigator and the sponsor's medical monitor independently assess causality; both assessments must be documented and both can be required in regulatory reports.
Question 6: In clinical trials, 'outcome' for an adverse event typically refers to which of the following classifications?
- Recovered/resolved, recovering/resolving, not recovered/not resolved, recovered with sequelae, fatal, unknown (Correct answer)
- Mild, moderate, severe, life-threatening, fatal
- Related, possibly related, unrelated, unknown
- Expected, unexpected, serious, non-serious
Correct answer: Recovered/resolved, recovering/resolving, not recovered/not resolved, recovered with sequelae, fatal, unknown
Standard AE outcome categories describe the resolution status of the event: recovered, recovering, not recovered, recovered with sequelae, fatal, or unknown.
CCRA Adverse Event Management 2
An 'adverse event of special interest' (AESI) differs from a standard SAE in that it: